A prospective study comparing water only with positive oral contrast in patients undergoing abdominal CT scan

Abstract

Consecutive adults scheduled to undergo abdominal CT with oral contrast were asked to choose between 1000 ml water only or positive oral contrast (50 ml Télébrix-Gastro diluted in 950 ml water). Two abdominal radiologists independently reviewed each scan for image quality of the abdomen, the diagnostic confidence per system (gastrointestinalsystem/organs/peritoneum/retroperitoneum/lymph nodes) and overall diagnostic confidence to address the clinical question (not able/partial able/fully able). Radiation exposure was extracted from dose reports. Differences between both groups were evaluated by Student’s t-test, Mann-Whitney-U-test or chi-square-test. Of the 320participants, 233chose water only. All baseline characteristics, image quality of the abdomen and the diagnostic confidence of the organs were comparable between groups and both observers. Diagnostic confidence in the water only group was more commonly scored as less than good by observer1. The results were as follows: the gastrointestinal system(18/233vs1/87; p = 0.031), peritoneum (21/233vs1/87; p = 0.012), retroperitoneum (11/233vs0/87; p = 0.040) and lymph nodes (11/233vs0/87; p = 0.040). These structures were scored as comparable between both groups by observer2. The diagnostic confidence to address the clinical question could be partially addressed in 6/233 vs 0/87 patients (p = 0.259). The water only group showed a tendency towards less radiation exposure. In summary, most scan ratings were comparable between positive contrast and water only, but slightly favored positive oral contrast for one reader for some abdominal structures. Therefore, water only can replace positive oral contrast in the majority of the outpatients scheduled to undergo an abdominal CT.

Full text

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A prospective study comparing
water only with positive oral
contrast in patients undergoing
abdominal CT scan
Pascale A. M. de Wit✉, Jeroen A. W. Tielbeek, Pascal R. van Diepen, Ikrame Oulad Abdennabi,
Ludo F. M. Beenen & Shandra Bipat
Consecutive adults scheduled to undergo abdominal CT with oral contrast were asked to choose
between 1000 ml water only or positive oral contrast (50 ml Télébrix-Gastro diluted in 950 ml water).
Two abdominal radiologists independently reviewed each scan for image quality of the abdomen,
the diagnostic condence per system (gastrointestinalsystem/organs/peritoneum/retroperitoneum/
lymph nodes) and overall diagnostic condence to address the clinical question (not able/partial able/
fully able). Radiation exposure was extracted from dose reports. Dierences between both groups
were evaluated by Student’s t-test, Mann-Whitney-U-test or chi-square-test. Of the 320participants,
233chose water only. All baseline characteristics, image quality of the abdomen and the diagnostic
condence of the organs were comparable between groups and both observers. Diagnostic condence
in the water only group was more commonly scored as less than good by observer1. The results were as
follows: the gastrointestinal system(18/233vs1/87; p = 0.031), peritoneum (21/233vs1/87; p = 0.012),
retroperitoneum (11/233vs0/87; p = 0.040) and lymph nodes (11/233vs0/87; p = 0.040). These structures
were scored as comparable between both groups by observer2. The diagnostic condence to address
the clinical question could be partially addressed in 6/233 vs 0/87 patients (p = 0.259). The water
only group showed a tendency towards less radiation exposure. In summary, most scan ratings were
comparable between positive contrast and water only, but slightly favored positive oral contrast for one
reader for some abdominal structures. Therefore, water only can replace positive oral contrast in the
majority of the outpatients scheduled to undergo an abdominal CT.
Background. CT protocols vary by institution, equipment, setting and clinical question. However, the default
abdominal CT protocol for outpatients regularly includes both oral contrast (either positive or negative) and an
intravenous contrast administration. e use of positive oral contrast in the outpatient setting has several direct
and indirect eects, such as increased costs, decreased practice eciency and patient inconvenience/discomfort.
e latter has been shown by Harieaswar et al.; patients rated oral contrast signicantly worse than intravenous
cannulation and injection1. e question arose whether oral contrast can be eliminated. e justication of omit-
ting oral contrast for emergency department patients has been questioned and extensively studied, leading to
withholding oral contrast in these patients2–5. However, it is not clear whether the advantages of withholding oral
contrast in the emergency department can be extrapolated to the outpatient setting, as they have dierent clinical
questions and patient spectrum. ere are no sucient data on withholding oral contrast in this patient popula-
tion6–9 and the available data are also equivocal.
Positive and Negative Oral Contrast. However several studies7–10 evaluated the role of ‘’negative oral
contrast” with water only and showed that the use of water only had similar image quality in follow-up abdomi-
nopelvic CT for general oncological indications7–9 and even better delineation8,10 and/or diagnosis compared to
“positive oral contrast”. Although limited data is available, it seems that positive oral contrast can be replaced by
water only, without losing image quality and the condence of the diagnosis.
Amsterdam UMC, University of Amsterdam, Department of Radiology & Nuclear Medicine, Meibergdreef 9, 1105,
AZ, Amsterdam, The Netherlands. ✉e-mail: p.a.dewit@amsterdamumc.nl
OPEN
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Radiation Exposure. Another issue associated with positive oral contrast, is the radiation exposure. One
study by Wang et al. showed higher radiation exposure for scans performed with positive oral contrast than those
with negative oral contrast in phantoms, respectively 8.7 ± 0.1 mGy, and 8.2 ± 0.2 mGy (6.1% higher than in water
only, p = 0.02). In patients these values were respectively 13.1 mGy and 11.8 mGy (11.0% higher than in water
only p = 0.003)11.
However, all the aforementioned data7–11 were retrospectively obtained and it is known that retrospective
studies have several limitations, such as selection bias, missing data and potential confounders. is makes the
implementation of the ndings of these studies in routine practice dicult.
Pilot Study. In the Netherlands many hospitals still use Télébrix Gastro as oral contrast agent for general
oncological/hematological indications.
Oral contrast has a predominant role in the evaluation of the gastrointestinal mucosa or bowel distension.
However, the focus for most outpatient scans is not the gastrointestinal mucosa and/or bowel distension, but on
the evaluation of visceral or metastatic disease. erefore, intravenous contrast is necessary12,13. is is the reason
we previously performed a single-centre, prospective pilot study14 including 50 consecutive adult outpatients (25
in each arm) undergoing a contrast-enhanced abdominal CT scan. In the pilot study we randomised positive
(50 ml Télébrix Gastro in 950 ml water) and water only as oral contrast (1000 ml water only). Two radiologists
independently rated scan quality and diagnostic condence by a validated 5-point scale system. Almost all qual-
ity and diagnostic condence scores were comparable between both observers and between both groups. One
observer scored the diagnostic condence of the gastrointestinal system as less than good in 10 of the patients
receiving water only as oral contrast. Patients’ discomfort in this pilot study was assessed by a questionnaire.
Although not statistically signicant, Télébrix Gastro was more unpleasant for patients (n = 16, severe/mild/less
than good) in comparison with water only (n = 12, severe/mild/less than good). Radiation exposure was extracted
from dose reports. In the Télébrix Gastro group, the mean total DLP was 719.3 ± 245.7 mGy*cm2 and in the water
only group 686.0 ± 206.9 mGy*cm2 (p = 0.62). e mean CTDIvol was 11.1 ± 3.7 mGy and 9.8 ± 2.6 mGy respec-
tively (p = 0.20). Although not signicant, there was a trend towards higher values in the positive oral contrast
group.
e pilot study showed that oral preparation with water only was just as sucient and safe as positive oral con-
trast preparation with Télébrix Gastro diluted in water. To validate the hypothesis that water only as oral contrast
is non-inferior to positive oral contrast preparation in abdominal CT, we performed a larger prospective study.
e aim of this prospective study was to compare the image quality rating, diagnostic condence per structure
in the abdomen, overall diagnostic condence to address the clinical question and radiation exposure between
water only and positive contrast (Télébrix Gastro diluted in water) as oral contrast agent in outpatients undergo-
ing abdominal CT.
Results
Patient population and selection. Four hundred ve (405) outpatients (age > 18 years) were scheduled to
undergo an abdominal CT scan with oral and intravenous contrast. Sixty (60) patients were excluded due to var-
ious reasons (Fig.1). 345 patients were asked to participate, of whom 24 did not want to participate. One patient
was excluded due to technical problems. Finally, 320 patients were included and 233 (72.8%) chose water only as
an oral contrast preparation. e remaining 87 patients (27.2%) chose positive oral contrast.
Patients and CT characteristics. All patient baseline characteristics (Table1) were comparable between
both groups (all p-values > 0.05), except the height, which was p = 0.049. e same accounts for the CT charac-
teristics (p > 0.05).
Exclusion (60)
23 patients were notabletogiveaninformed consent
due rescheduledappointment
12 patients didnot received theinformation letter
9patients wherethe standard protocol waschanged
8patientsdid notvisit theappointment
1patient receivedoralcontrastelsewhere
4patients were notableto understand thepatient
informationletter(either duetolanguagebarrier,
dyslecticorblind)
3patients were included in thestudy (earlier in FU )and
undergoscanningwithin3months
Exclusion (25)
24 patients whodid not want to participate
1scan wasfailedbecause of technicalproblems
345 patientswereasked to participate
320 patientswere included
233 patientschose water only
87 patientschose positive oral contrast
405 outpatientswithanage of ≥18
years were scheduled to undergoan
abdominalCT with oral andintravenous
contrast.
Figure 1. Selection and inclusion of patients.
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Radiation exposure. Although not signicant, all medians (except CTDIvol in the chest/abdomen region)
were higher in the positive oral contrast group scanned by 64 slice scanners (Table2). e medians of the total
DLP and CTDIvol of the dierent regions scanned by the 128 and 2*192 slice scanners seem comparable between
the two oral contrast groups (Table3), but this might be explained by the low number of patients.
Image quality of the abdomen. e agreement between the observers was 86.9% (53/61). ere was no
dierence between the water only and positive contrast for both observer 1 and observer 2 (p-values were respec-
tively 0.574 and 0.310) (Figs.2 and 3).
Diagnostic condence per structure of abdomen. Gastrointestinal system. e agreement between
the observers for the evaluation of the diagnostic condence was 90.3% (289/320). Observer 1 scored signicantly
more scans as less than good in the water only group compared to the positive contrast group (18/233 vs 1/87);
p = 0.031. Observer 2 scored comparable diagnostic condence of the gastrointestinal system between water only
and the positive contrast groups (p = 0.634) (Fig.4a).
Organs. The agreement between the observers for the evaluation of the diagnostic confidence was 97.5%
(312/320). e diagnostic condence was comparable between the water only and positive contrast groups, as
assessed by observer 1 (p = 1.000) and observer 2 (p = 0.063) respectively (Fig.4b).
Peritoneum. e agreement between the observers for the evaluation of the diagnostic condence was 90.9%
(291/320). Observer 1 scored signicant more scans as less than good in the water only group compared to the
positive contrast group (21/233 vs 1/87); p = 0.012. Observer 2 scored comparable diagnostic condence of the
gastrointestinal system between water only and the positive contrast groups (p = 1.000) (Fig.4c).
Water only as oral contrast:1000 ml water
(n = 233) Positive oral contrast: 50 ml Télébrix Gastro
diluted in 950 ml water (n = 87) p-values
Sex distribution (male: female) 130:103 40:47 0.117
Age in years* (mean ± SD) 62.7 ± 12.17 62.9 ± 13.78 0.895
Height in cm* (mean ± SD) 174.3 ± 9.82 171.8 ± 9.69 0.049
Weight in kg* (mean ± SD) 78.0 ± 16.71 75.2 ± 14.98 0.178
BMI (kg/m2)* (mean ± SD) 25.7 ± 5.00 25.4 ± 4.15 0.609
Patient spectrum
Oncology: n = 200 (85.8%) Oncology: n = 71 (81.6%)
0.124Haematology: n = 12 (5.2%) Haematology: n = 10 (11.5%)
Others: n = 21 (9.0%) Others: n = 6 (6.9%)
Region scanned
Neck/Chest/Abdomen: n = 43 (18.5%) Neck/Chest/Abdomen: n = 23 (26.4%)
0.200Chest/abdomen: n = 147 (63.0%) Chest/abdomen: n = 46 (52.9%)
Abdomen: n = 43 (18.5%) Abdomen: n = 18 (20.7%)
CT scanner 64 slice scanners: n = 202 (86.7%) 64 slice scanners: n = 80 (92.0%) 0.196
128 and 2*192 slice scanner: n = 31 (13.3%)** 128 and 2*192 slice scanner: n = 7 (8.0%)**
Table 1. Baseline patients and CT characteristics. *Age, height, weight, BMI and time interval were normally
distributed. **Due to the low number of patients scanned on the 128 and 2*192 slice scanners, these data were
combined.
Water only as oral contrast:1000 ml
water(n = 199)*Positive oral contrast: 50 ml Télébrix
Gastro diluted in 950 ml water(n = 79)*p-values
Total DLP in milligray*centimeters
(median + range)
Neck/Chest/Abdomen (n = 37):
775.4 (420.0–1383.6) Neck/Chest/Abdomen (n = 21)
815.4 (407.9–1167.8) 0.994
Chest/abdomen (n = 125):
722.1 (327.3–1547.5) Chest/abdomen (n = 41):
725.6 (328.0–1442.4) 0.877
Abdomen (n = 37):
509.5 (329.4–1563.0) Abdomen (n = 17):
650.2 (279.8–1035.2) 0.703
CTDIvol in milligray
(median + range)
Neck/Chest/Abdomen (n = 37):
9.11 (5.18–17.32) Neck/Chest/Abdomen (n = 21):
9.51 (5.01–13.06) 0.815
Chest/abdomen (n = 125):
10.53 (4.90–21.12) Chest/abdomen (n = 41):
10.27 (5.81–19.85) 0.863
Abdomen (n = 37):
10.31 (6.26–26.81) Abdomen (n = 17):
11.40 (6.35–18.61) 0.485
Table 2. Radiation exposure in patients per region scanned by 64 slice scanners. All data were non-normally
distributed and therefore Mann-Whitney test was performed to compare the distribution between the two arms.
*Data on 4 patients were not taken into account, as they did undergo additional phase scanning.
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Retroperitoneum. e agreement between the observers for the evaluation of the diagnostic condence was
96.3% (308/321). Observer 1 scored signicant more scans as less than good in the water only group compared to
the positive contrast group (11/233 vs 1/87); p = 0.040. Observer 2 scored comparable diagnostic condence of
the gastrointestinal system between water only and the positive contrast groups (p = 0.272) (Fig.4d).
Lymph nodes. e agreement between the observers for the evaluation of the diagnostic condence was 96.3%
(308/321). Observer 1 scored signicant more scans as less than good in the water only group compared to the
positive contrast group (11/233 vs 1/87); p = 0.040. Observer 2 scored comparable diagnostic condence of the
gastrointestinal system between water only and the positive contrast groups (p = 0.272) (Fig.4e).
Overall diagnostic condence to address the clinical question. e agreement between the two
observers for the evaluation of the overall diagnostic condence was 96.3% (308/321; 307 fully addressing the
clinical question and 1 partially addressing the clinical question). ere were no scans where the clinical question
could not be addressed. Observer 1 scored 8 scans as partially addressing the clinical question in patients with
water only. Observer 2 scored 6 scans, 4 scans of patients with water only and 2 patients with positive oral contrast
agent, as partially addressing the clinical question. In total, 13 patients, 11 with water only and 2 with positive oral
contrast were rechecked by observer 3 (Table4).
In 7 patients (5 with water only and 2 patients with positive oral contrast), the clinical question could be
answered by observer 3. e remaining 6 scans were also scored as partially addressed by observer 3. A total of
6/233 vs 0/87 were scored as partially addressed (p = 0.259). Scans that partially addressed the clinical questions,
were due to; 1) diculties in evaluating peritoneal and/or omental depositions; 2) stulas and liquid collections;
and 3) diculties in performing mass measurement if located close to or merged with the intestine.
Discussions
Summary. We found that outpatients undergoing abdominal CT scan preferred water only as oral contrast
above the positive oral contrast. is does not inuence image quality. One observer experienced slightly less con-
dence in the evaluation of the GI tract, peritoneum, retroperitoneum and lymph nodes; this might be explained
by the lower experience of the observer.
In addition, the clinical question could be fully addressed in the majority of patients. Only 6/233 in the water
only group vs 0/87 in the positive oral contrast group were scored as partially addressed. In none of the patients,
could the clinical questions not be addressed. Scans that only partially addressed the clinical questions were due
to the diculties in evaluating peritoneal and/or omental depositions; stulas and liquid collections; and mass
Water only as oral contrast: 1000 ml water
(n = 31) Positive oral contrast: 50 ml Télébrix
Gastro diluted in 950 ml water (n = 7) p-values
Total DLP in milligray*centimeters
(median + range)
Neck/Chest/Abdomen (n = 6) 575.6 (367.0–652.5) Neck/Chest/Abdomen (n = 1) 533.1*1.000
Chest/abdomen (n = 20) 422.3 (214.7–755.1) Chest/abdomen (n = 5) 415.0
(242.1–566.6) 0.530
Abdomen (n = 5) 278.2 (213.2–462.7) Abdomen (n = 1) 266.2*0.667
CTDIvol in milligray(median + range)
Neck/Chest/Abdomen (n = 6) 7.02 (4.58–8.43) Neck/Chest/Abdomen (n = 1) 6.13*0.857
Chest/abdomen (n = 20) 6.12 (4.36–11.88) Chest/abdomen (n = 5) 6.70 (3.66–8.10) 0.921
Abdomen (n = 5) 6.33 (4.96–8.37) Abdomen (n = 1) 5.30*0.667
Table 3. Radiation exposure in patients per region scanned by 128 and 2*192 slice scanners. All data were non-
normally distributed and therefore Mann-Whitney test was performed to compare the distribution between the
two arms. *n = 1, therefore no range can be given.
5% 11% 9%
0%
95%89% 91%
100%
0%
20%
40%
60%
80%
100%
Water Obs 1Positive contrast Obs 1Water Obs 2Positive contrast Obs 2
Moderate Good + very good
Figure 2. e quality of de scans assessed by observer 1 and observer 2.
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measurement if located close to or merged with the intestine, due to missing positive oral contrast. ere was
no signicant dierence in radiation exposure between both groups. However, the positive oral group showed a
tendency towards a higher radiation exposure.
Compared to other studies. In several studies, the role of water only as oral contrast has been evaluated7–10.
In the study of Kammerer et al.7, mainly oncology patients (68%), with dierent types of oral preparation
(positive contrast agent, n = 576; water only, n = 716; and no oral contrast, n = 716) were retrospectively evalu-
ated. Delineation of the bowel was evident across all segments regardless of the type of oral contrast and a slight
impairment (concerning diagnostic reliability) was observed in patients without the use of any oral contrast.
In the study of Buttigieg et al.8, 46 oncological patients who previously underwent abdominopelvic CT with
positive oral contrast, were scheduled for follow-up and received water only as oral contrast (n = 25) or no oral
contrast agent (n = 21). e data showed comparable image quality concerning the reproduction of abdominal
structures, bowel discrimination, presence of artefacts, and visualization of the amount of intra-abdominal fat
for the three protocols.
e study by Lee et al.9, with 103 patients who received both (water only and positive oral contrast) strategies
also showed signicantly better delineation of duodenal wall (p < 0.001), and overall visualisation of the duo-
denum (p = 0,001), using water only compared to positive oral contrast including Télébrix Gastro. Comparable
results were observed for visualisation of the other abdominopelvic organs, wall delineation of the small bowel
and contrast-associated artefacts.
Makarawo et al.10 studied image clarity and luminal distention in 66 patients who received both a pancreas
protocol CT (PPCT) that uses oral water and abdominal conventional positive oral contrast scan. CT images were
independently reviewed by two radiologists who scored the degree of hollow viscus distention and visualization
of mural detail using a Likert 5-point scale. e PPCT had a better median score for organ clarity in the stomach
and duodenum (P < 0.001) and better luminal distention in the stomach (P < 0.001), equal distention in the duo-
denum (P = 0.02), and slightly worse distention in the ileum (P = 0.02). e remaining bowel and organs were
evaluated with no statistically signicant dierence in the ratings between the two protocols. ey concluded that
using present CT scan technology, water can be an eective contrast medium causing better or equal distention
in the bowel and better or equal clarity than routine barium contrast.
However, all data of the above-mentioned studies7–10 was retrospectively obtained. In our previous prospective
pilot study14 including 50 consecutive adult outpatients (25 in each arm), quality and diagnostic condence scores
were comparable between water and positive oral contrast. Positive oral contrast caused more discomfort (n = 16,
severe/mild/less than good) in comparison with water only (n = 12, severe/mild/less than good).
Concerning the radiation exposure, one study by Wang et al.11 showed higher radiation exposure for scans
performed with positive oral contrast than those with water as oral contrast in respectively 13.1 mGy and
11.8mGy (p = 0.003). In our previous study14, the mean total DLP was 719.3 ± 245.7 mGy*cm2 and 686.0 ± 206.9
mGy*cm2 (p = 0.62) in the Télébrix Gastro and water only respectively. e mean CTDIvol was 11.1 ± 3.7 mGy
and 9.8 ± 2.6 mGy respectively (p = 0.20). In this study, although not signicant, there was also a trend towards
higher values in the positive oral contrast group. e ndings of this study concerning the image quality, diagnos-
tic condence and the diagnostic reliability (clinical question) and radiation exposure were in line with the results
of all the above mentioned studies7–11.
Strengths. To our knowledge this is the rst large prospective study performed on this topic. e advice of
oral contrast preparation dates back to the year 200015. We did not only evaluate the image quality and diagnostic
condence, but also the overall diagnostic condence and the radiation exposure. Two abdominal radiologists
with dierent levels of experience reviewed all of the scans independently.
Figure 3. CT images of two patients with either water only or Télébrix Gastro as oral contrast. (A) shows
an axial image of an abdominal CT of a 72-year-old man with metastatic renal cell carcinoma where the
gastrointestinal tract was lled with water only (grey lumen). (B) shows an axial image of an abdominal CT of
a 65-year-old man colorectal liver metastasis where the gastrointestinal tract was lled with Télébrix Gastro
(white lumen).
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Limitations. ere were some limitations in the present study. is study is not a randomised controlled trial
but a prospective case-control study. is design was selected, as both types of contrast agents were used to a dif-
ferent extent in the general practice and we also aimed to study the preference of patients. Although patients were
free to choose between water only and Télébrix Gastro as oral contrast, we do not think this generated a high risk
of bias, as baseline characteristics were comparable. We excluded patients with a primary gastro-intestinal indica-
tion. It is known that opacication of the gastrointestinal (GI) system by water only eects the diagnosis of the GI
system12,13. However, the patient population in our study consist of mainly oncological patients where the focus
lies on metastases and not on the GI tract. For the specic interpretation of GI systems (for e.g. polyps or Crohn’s
disease), regular CT scans are not sucient and more specic imaging is needed, such as CT enterography or
AB
CD
E
8% 1% 8% 6%
92%99%92%94%
0%
20%
40%
60%
80%
100%
Water Obs
1
Positive
contrast
Obs 1
Water Obs
2
Positive
contrast
Obs 2
Diagnostic confidence of the
gastrointestinal system
Moderate Good + very good
1% 1% 0% 3%
99%99%100% 97%
0%
20%
40%
60%
80%
100%
Water Obs
1
Positive
contrast
Obs 1
Water Obs
2
Positive
contrast
Obs 2
Diagnostic confidence of the
organs
Moderate Good + very good
9% 1% 6% 5%
91%99%94%95%
0%
20%
40%
60%
80%
100%
Water Obs
1
Positive
contrast
Obs 1
Water Obs
2
Positive
contrast
Obs 2
Diagnostic confidence of the
peritoneum
Moderate Good + very good
5% 0% 0% 1%
95%100% 100% 99%
0%
20%
40%
60%
80%
100%
Water Obs
1
Positive
contrast
Obs 1
Water Obs
2
Positive
contrast
Obs 2
Diagnostic confidence of the
retroperitoneum
Moderate Good + very good
5% 0% 0% 1%
95%100% 100% 99%
0%
20%
40%
60%
80%
100%
Water Obs
1
Positive
contrast
Obs 1
Water Obs
2
Positive
contrast
Obs 2
Diagnostic confidence of the
lymph nodes
Moderate Good + very good
Figure 4. e diagnostic condence of the dierent regions by observer 1 and observer 2.
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colography. Finally, later emerging contra-indications like diarrhea, nausea or vomiting were not taken into con-
sideration in this study16. e current study focuses only on subjective grading of image quality and diagnostic
condence, and does not test miss-rates for disease. Ultimately, the miss-rate of bowel and peritoneal disease is
the most important end point, and will require larger numbers of scans and appropriate follow-up studies in the
future.
Conclusions
We found that abdominal CT with water only has comparable diagnostic condence as abdominal CT with pos-
itive oral contrast in the majority of outpatients. erefore, water only can replace positive oral contrast in the
standard CT protocol for the majority of outpatients scheduled to undergo an abdominal CT.
Materials and Methods
This study was conducted according to the principles of the Declaration of Helsinki (64th WMA General
Assembly, Fortaleza, Brazil, October 2013) and a waiver concerning the Medical Research Involving Human
Subjects Act (WMO) regulation was obtained. is study is reported according to Strobe (Strengthening the
Reporting of Observational Studies in Epidemiology) guidelines17.
Population. Consecutive adult outpatients that were scheduled to undergo an abdominal CT scan with
oral and intravenous contrast at the department of Radiology and Nuclear Medicine between June 2018 and
September 2018 were included. The indications for abdominal CT scan with oral contrast were: follow-up
oncology, chronic pancreatitis, pseudocyst, follow-up hepatopancreaticobiliary (HPB) surgery and hematology.
Inclusion criteria were: (1) patients scheduled to undergo an abdominal CT scan (with or without neck and
chest scan) with oral and intravenous contrast; (2) outpatients and (3) age ≥18 years. Exclusion criteria were: (1)
patients undergoing CT for research purposes; (2) patients who were not able to drink; and (3) patients requir-
ing positive oral contrast for evaluation of the gastrointestinal/intraluminal tract (primary staging and response
monitoring of colon tumour, staging of inammatory bowel disease, evaluation of anastomotic leaks, evaluation
of gastrointestinal stromal tumour) and patients with complex problems (cause unknown).
Procedure. Patients scheduled to undergo contrast-enhanced abdominal CT scan and fullling inclusion cri-
teria received a letter 5–8 days before the scheduled CT scan. Patients were asked to choose between water only as
oral contrast (1000 ml water) or positive oral contrast (50 ml Télébrix Gastro (Guerbet, Villepinte, France) diluted
in 950 ml water), as both methods are general accepted methods in e Netherlands. Written informed consent
for the use of data was obtained before the CT scan started. Patients who chose water only were instructed to
drink this volume in 45 minutes. e patients who chose positive oral contrast (50 ml Télébrix Gastro + 950 ml
water) were instructed to drink within 60 minutes as standard protocol. No adjustments were made concerning
intravenous administration of the contrast agent.
CT acquisition. CT scans were performed according to our routine protocol, using 4 dierent CT systems.
Two 64 slice systems (SOMATOM Sensation, Siemens Healthcare, Erlangen, Germany and Philips Brilliance,
Philips Medical Systems, Best, e Netherlands), one 128 slice system (SOMATOM Denition AS + , Siemens
Healthcare, Erlangen, Germany) and one dual source 2*192 slice system (SOMATOM Force, Siemens Healthcare,
Erlangen, Germany) were used. Iomeron (300 mg I/ml, Bracco UK limited, High Wycombe, UK) was used as
intravenous contrast agent. e intravenous scan protocol for the SOMATOM Force contains 80 ml Iomeron. e
other three scanners (Sensation, Denition AS + , and Brilliance) used 100 ml Iomeron.
Patient
number
Water only
or positive
contrast Patient
Spectrum Age in
years Sex (male
or female) Observer 1 Observer 2 Obs erver 3
1Water only Oncology 79.3 Female Partially addressed Fully addressed Fully addressed
2Water only Oncology 77.6 Male Partially addressed Fully addressed Partially addresse d
3Water only Oncology 63.7 Male Partially addressed Fully addressed Partially addresse d
4Water only Other 66.5 Male Fully addressed Partially addressed Partially addressed
5Water only Oncology 64.8 Female Fully addressed Partially addressed Partially addressed
6Water only Oncology 65.9 Male Partially addressed Partially addressed Partially addressed
7Water only Other 71.7 Female Partially addressed Fully addressed Fully addressed
8Water only Oncology 65.9 Female Partially addressed Fully addressed Fully addressed
9Water only Oncology 81.5 Female Fully addressed Partially addressed Partially addressed
10 Water only Oncology 72.3 Female Partially addressed Fully addressed Fully addressed
11 Water only Other 68.9 Male Partially addressed Fully addressed Fully addressed
12 Positive oral
contrast Other 49.7 Female Fully addressed Partially addressed Fully addressed
13 Positive oral
contrast Oncology 78.4 Female Fully addressed Partially addressed Fully addressed
8 of 13 partially
addressed 6 of 13 partially
addressed 6 of 13 partially
addressed
Table 4. Patients with partially assessed overall diagnostic condence by either observer.
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Sample size calculation. In the pilot study14, the percentage of overall diagnostic condence was rated as
good in 98.4% and 94.4% patients with respectively positive oral contrast and water only. Based on these ndings
and a non-inferiority design, we had to include at least 210 patients (water only group) with a power of 90% (90%
sure) and an upper limit of one-sided 95% condence interval to exclude a dierence in favour of the standard
group of more than 4%.
Data-extraction. Age, sex, height, weight, patient spectrum (oncological, haematological or other), scanned
regions and CT scanner system were extracted/reported.
Radiation exposure measures such as CTDIvol (volume CT dose index) and DLP (Dosis Length Product) were
extracted from radiation exposure reports of each scanner. In our institution, a dose report is electronically cap-
tured for all CT exams with CTDIvol and DLP18.
Data evaluation. Two abdominal radiologists, with respectively 6 years (observer 1) and 19 years (observer
2) experience in evaluating abdominal scans, reviewed each image set independently. Images were presented in
a random order and blinding of the images was not necessary as high attenuation images with positive oral con-
trast were being compared to images with water only as oral contrast and this could not be concealed. ey rated
the image quality of the abdomen, the diagnostic condence per structure in the abdomen and nally an overall
diagnostic condence to address the clinical question.
Image quality of the abdomen. Image quality of the abdomen was assessed according to an ordinal rating scale
of ve response categories; (1) very poor; (2) poor; (3) less than good; (4) good and; (5) very good, adapted from
Båth and Månsson19.
Diagnostic condence per structure in the abdomen. e diagnostic condence per system was also rated accord-
ing to the same 5-point scale. e following ve systems were rated;(1) gastrointestinal system (stomach, duo-
denum, jejunum, ileum, colon and appendix); (2) organs (liver, spleen, pancreas, adrenals, gallbladder, kidneys
including ureters, bladder, ovaries, uterus or prostate); (3) peritoneum; (4) retroperitoneum; and (5) lymph
nodes9.
Overall diagnostic condence to address the clinical question. An overall diagnostic condence was assessed using
a 3-point scale; 1) not able; 2) partially able; and 3) fully able to address the clinical question. Any scan scored
as partially able to address the clinical question by one of the two radiologists was checked independently by a
third abdominal radiologist (observer 3) with experience in abdominal CT reporting of 7 years. e abdominal
radiologist had to score the scans by choosing; 1) partially able; and 2) fully able to address the clinical question.
Statistical analysis. Patients and CT characteristics. Baseline data was summarized using descriptive
statistics. Both groups were compared using the Student’s t-test statistic (normal distributed continuous data),
Mann-Whitney U-test (non-normal distributed continuous data) or chi-squared test for categorical data. And the
medians and ranges of the total DLP and CTDIvol of the dierent regions between the two groups were compared
by using the Mann-Whitney test.
Study parameters. e results of image quality and diagnostic condence per structure between the two groups
were expressed as proportion and corresponding 95% condence intervals. ese data were categorised in three
categories (1 and 2, 3, 4 and 5) and null hypothesis of no dierence was evaluated by chi-squared test for trend,
due to the ordinal character of the data. Agreement between observers was expressed as percentages.
e results on overall diagnostic condence (not able, partially able or fully able to address the clinical ques-
tion) were expressed as proportion of corresponding 95% condence interval and evaluated by chi-squared test.
Agreement between the observers was expressed as percentages.
Data availability
e datasets used and/or analysed in this study are available from the corresponding author on reasonable
request.
Received: 30 July 2019; Accepted: 16 January 2020;
Published: xx xx xxxx
References
1. Harieaswar, S., ajesh, A., Grin, Y., Tyagi, . & Morgan, B. outine use of positive oral contrast material is not required for
oncology patients undergoing follow-up multidetector CT. adiology. 250, 246–253 (2009).
2. Payor, A. et al. Ecacy of Noncontrast Computed Tomography of the Abdomen and Pelvis for Evaluating Nontraumatic Acute
Abdominal Pain in the Emergency Department. J. Emerg. Med. 49, 886–892 (2015).
3. azavi, S. A., Johnson, J. O., assin, M. T. & Applegate, . E. e impact of introducing a no oral contrast abdominopelvic CT
examination (NOCAPE) pathway on radiology turn around times, emergency department length of stay, and patient safety. Emerg.
adiol. 21, 605–613 (2014).
4. Wolfe, J. M. et al. e impact of body mass index on concordance in the interpretation of matched noncontrast and contrast
abdominal pelvic computed tomographic scans in ED patients with nontraumatic abdominal pain. Am. J. Emerg. Med. 24, 144–148
(2006).
5. Uyeda, J. W. et al. Evaluation of Acute Abdominal Pain in the Emergency Setting Using Computed Tomography Without Oral
Contrast in Patients With Body Mass Index Greater an 25. J. Comput. Assist. Tomogr. 39, 681–686 (2015).
6. Garcia, C. M. et al. e Impact of Enteric Contrast on adiologist Condence in Intravenously Enhanced MDCT of the Abdomen
and Pelvis: A andomized Controlled Trial. Advances in Computed Tomography 3, 18–23 (2014).
Content courtesy of Springer Nature, terms of use apply. Rights reserved

9
SCIENTIFIC REPORTS | (2020) 10:6813 | https://doi.org/10.1038/s41598-020-63838-3
www.nature.com/scientificreports
www.nature.com/scientificreports/
7. ammerer, S. et al. Abdominal and pelvic CT: is positive enteric contrast still necessary? esults of a retrospective observational
study. Eur. adiol. 25, 669–78 (2015).
8. Buttigieg, E. L., Grima, . B., Cortis, ., Soler, S. G. & Zarb, F. An evaluation of the use of oral contrast media in abdominopelvic CT.
Eur. adiol. 24, 2936–2944 (2014).
9. Lee, C. H., Gu, H. Z., Vellayappan, B. A. & Tan, C. H. Water as neutral oral contrast agent in abdominopelvic CT: comparing
eectiveness with Gastrogran in the same patient. Med. J. Malaysia. 71, 322–327 (2016).
10. Maarawo, T. P. et al. Water as a contrast medium: a re-evaluation using the multidetector-row computed tomography. Am. Surg. 79,
728–733 (2013).
11. Wang, Z. J. et al. Positive enteric contrast material for abdominal and pelvic CT with automatic exposure control: what is the eect
on patient radiation exposure? Eur.J. adiol. 79, e58–62 (2011).
12. ambadaone, A.. & Sahani, D.V. Multi-detector Computed Tomography in the Gastrointestinal System in MDCT (ed. alra,
M..) 138-159 (Springer, Milano. 2008).
13. Elamparidhi, P., Sivaranjanie, S., umar, . ., Sibhithran, . & umar, A. A. Comparison of Water, Mannitol and Positive Oral
Contrast for Evaluation of Bowel by Computed Tomography. International Journal of Anatomy, adiology and Surgery 6,
O13–O17 (2017).
14. de Wit, P.A.M, van Dij, J.W., Somers, I., Beenen, L.F.M. & Bipat, S. A pilot study comparing two strategies of oral contrast in
patients undergoing abdominal CT: 50 ml Télébrix Gastro + 950 ml water vs 1000 ml water only. Unpublished data.
15. European Commission European guidelines on quality criteria for computed tomography, EU 16262EN. Luxembourg (2000).
16. Guerbet Summary of product characteristics Télébrix Gastro, 300 mg I/ml solution for injection. Guerbet, Cedex (2015).
17. Vandenbrouce, J. P. et al. Strengthening the eporting of Observational Studies in Epidemiology (STOBE): explanation and
elaboration. Int. J. Surg. 12, 1500–1524 (2014).
18. Huda, W. & Metller, F. A. Volume CT Dose Index and Dose-Length Product Displayed during CT: What Good Are ey? adiology.
258, 236–242 (2011).
19. Båth, M. & Månsson, L. G. Visual grading characteristics (VGC) analysis: a non-parametric ran-invariant statistical method for
image quality evaluation. Br. J. adiology. 80, 169–176 (2007).
Acknowledgements
We would like to thank Lewis Knight for critical review of the manuscript and for correction of the English text.
Author contributions
P.A.M.d.W., J.A.W.T., P.R.v.D., I.O.A., L.F.M.B. and S.B. were responsible for the study design and concept. P.A.M.
d.W., J.A.W.T., L.F.M.B. and S.B. collected all data. P.A.M.d.W. and S.B. performed the data-analysis (statistical
analysis). P.A.M.d.W., J.A.W.T., P.R.v.D., I.O.A., L.F.M.B. and S.B. did the interpretation of data. P.A.M.d.W. and
S.B. performed the manuscript preparation. P.A.M.d.W., J.A.W.T., P.R.v.D., I.O.A., L.F.M.B. and S.B. performed
the manuscript edition and approved the nal version of the manuscript for submission.
Competing interests
e authors declare no competing interests.
Additional information
Correspondence and requests for materials should be addressed to P.A.M.d.W.
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