Introduction
Therapeutic endoscopic ultrasound (t-EUS) procedures are increasingly being adopted
in the daily clinical practice at tertiary referral centers [1 ]. However, little is known about radiation exposure (RE) for patients and physicians
involved with these procedures, mostly regarding an era in which lumen apposing metal
stents (LAMS) were not yet available. While the International Commission on Radiological
Protection recommends use of diagnostic reference levels to monitor the real-world
clinical practice of procedures involving fluoroscopy, no standard diagnostic reference
levels are available for t-EUS [2 ].
The aim of this study was to analyze the RE of modern t-EUS procedures involved in
biliary drainage, gastric outlet obstruction, and acute cholecystitis management.
Methods
This was a retrospective evaluation of a prospectively maintained database of all
consecutive t-EUS procedures performed in San Raffaele Institute between 2019 and
2021, performed in a dedicated room with a mobile, under-couch, C-arm fluoroscopic
system (Ziehm Vision RFD, Reggio Emilia, Italy).
T-EUS procedures
Information on procedures was retrieved through electronic search of an endoscopic
reporting program (Endox, TESI, Milan, Italy) in which t-EUS procedures are grouped
together under the same label (EUS-guided drainage). EUS-guided choledochoduodenostomy
(EUS-CDS), fluid collection drainage (EUS-FCD), gallbladder drainage (EUS-GBD), hepaticogastrostomy
(EUS-HGS) and gastroenterostomy (EUS-GE) were included.
All procedures were performed by three experienced therapeutic endosonographers (PGA,
MCP, GV) who completed their training in each performed procedure before the study
interval. No significant change has been introduced during the study interval in the
technical phases or devices used for each individual procedure.
Briefly, in our Institution EUS-CDS and EUS-GBD are usually performed through free-hand
placement of electrocautery-enhanced LAMS. EUS-FCD are performed either by free-hand
LAMS placement (necrotic collections) or with double-pigtail plastic stents (DPPS)
through a sequence involving needle-guidewire-cystotome-stent (homogeneously fluid
collections) [3 ]. For EUS-GBD and EUS-FCD with LAMS, we usually place coaxial DPPS, for which fluoroscopy
is used according to endoscopist preference. EUS-GE is usually performed through the
wireless simplified technique (WEST) i. e. through free-hand LAMS placement after
jejunal distention through an oro-jejunal tube [4 ]. EUS-HGS is performed through a needle-guidewire-cystotome-stent sequence, using
a purpose-specific partially-covered metal stent [5 ].
Technical steps deviating from the above-mentioned standard techniques (e. g. LAMS
placement over a guidewire; misdeployments; additional stents placement) were registered
as “intraprocedural troubles” and reported in detail.
Comparators
For t-EUS procedures having a standard endoscopic alternative, we identified an equivalent
number of cases performed for the same indication, during the same interval, using
the same fluoroscopic machinery: for EUS-CDS, an equal number of ERCPs with metal
stenting for distal malignant biliary ostruction; for EUS-GE, an equivalent number
of duodenal stenting for malignant antro-duodenal obstruction. Baseline characteristics
between the groups are compared in Supplementary Table 1 and Supplementary Table 2 .
Radiologic exposure metrics
RE was evaluated based on three cumulative RE metrics. Fluoroscopy time (FT) measured
in seconds. Cumulative Air Kerma (Ka,ref , where Kerma stands for kinetic energy released in a mass) measured in mGy as an
indicator of cumulative dose at a fixed interventional reference point. Kerma-Area
product (KAP) measured in Gy·cm2 represents the product of Ka,ref integral and the beam area in a plane perpendicular to the beam axis, and is a more
reliable estimator of the radiation dose received by the patient [2 ].
Variables
Together with RE dose metrics, the following variables were extracted: demographic
characteristics of patients (age, sex), underlying disease, technical success (yes/no),
and intraprocedural troubles (yes/no).
Intraprocedural troubles (e. g. stent misdeployment; LAMS placement over a guidewire;
placement of additional stents) were registered as reported in the Exam Report. Procedures
without any reported inconveniences were defined as “Trouble-free.”
Statistics
Mann-Whitney-U and Kruskal-Wallis tests were used as appropriate for comparing RE
metrics of different t-EUS procedures, and of t-EUS procedure versus a standard endoscopic
alternative. KAP values distribution are shown as box-and-whiskers plots.
Ethics
All patients provided written informed consent. This research was conducted under
the PROTECT Protocol (Local IRB approval ID: 178/INT/2020, Clinical Trial Identifier:
NCT04813055).
Results
A total of 141 t-EUS procedures were performed during the study interval (EUS-CDS = 44;
EUS-FCD-DPPS = 28; EUS-FCD-LAMS = 26; EUS-GE = 27; EUS-HGS = 10; EUS-GBD = 6). During
the same timeframe, 44 ERCPs and 27 duodenal stent placements were selected as controls
as previously described, for a total of 212 included procedures.
Patients’ characteristics are reported in [Table 1 ]. Median age was 66 ( range 58–73), 57 % were male, 65 % had pancreatic cancer and
26 % had a peripancreatic fluid collection.
Table 1
Characteristics of included patients.
Variable
Total
N = 212
Only t-EUS procedures
N = 141
Age, median [IQR]
66 [58–73]
66 [58–73]
Male, n (%)
120 (56.6 %)
77 (54.6 %)
Primary disease
Pancreatic cancer
138 (65.1 %)
69 (48.9 %)
Peripancreatic fluid collections
54 (25.5 %)
54 (38.3 %)
Pseudocyst/postsurgical/WOPN
30/17/7
30/17/7
Cholangiocarcinoma
6 (2.8 %)
6 (4.3 %)
Acute cholecystitis
4 (1.9 %)
4 (2.8 %)
Others (among others duodenal/gastric/ovarian cancer)
10 (4.3 %)
8 (5.7 %)
Procedure
Technical Success
EUS-choledochoduodenostomy, n (%)
44 (20.8 %)
43 (97.7 %)
ERCP with SEMS, n (%)
44 (20.8 %)
EUS-FCD-DPPS, n (%)
28 (13.2 %)
28 (100 %)
EUS-FCD-LAMS, n (%) – coaxial DPPS = 96.2 %
26 (12.3 %)
26 (100 %)
EUS-gastroenterostomy, n (%)
27 (12.7 %)
26 (96.3 %)
Duodenal stent, n (%)
27 (12.7 %)
EUS-hepaticogastrostomy, n (%)
10 (4.7 %)
9 (90 %)
EUS-gallbladder drainage, n (%)
6 (2.8 %)
6 (100 %)
ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound;
DPPS, double-pigtail plastic stent; FCD, fluid collection drainage; IQR, interquartile
range; LAMS, lumen apposing metal stent; SEMS, self-expandable metal stent; t-EUS,
therapeutic EUS; WOPN, walled-off pancreatic necrosis.
Technical success rates were 100 % for EUS-FCD-DPPS, EUS-FCS-LAMS and EUS-GBD, 97.7 %
for EUS-CDS, 96.3 % for EUS-GE and 90 % for EUS-HGS.
KAP, Ka,ref and FT were respectively available for 84.4 %, 96.2%, and 100 % of the procedures.
Radiation exposure
RE metrics are shown in [Table 2 ] and [Fig. 1 ].
Table 2
Radiologic exposure metrics. Median values and interquartile range of each RE metrics
according to specific endoscopic procedure are reported.
Variable
Air Kerma (mGy)
P value
Kerma Area Product (Gy·cm2 )
P value
Fluoroscopy Time (s)
P value
Overall
< 0.000001; For trend 0.03
Overall
< 0.000001; For trend 0.0003
Overall
< 0.000001; For trend 0.003
EUS-Choledochoduodenostomy
0 [0–2]
< 0.0001
0 [0–0]
< 0.0001
0 [0–2]
< 0.0001
ERCP with SEMS, median [IQR]
237 [161–452]
25.44 [17.21–54.84]
97 [71–192]
EUS-FCD-LAMS, median [IQR]
0 [0–0]
0 [0–0]
0 [0–0]
EUS-GBD, median [IQR]
43 [3–155]
8.58 [2.45–20.58]
16 [2–60]
EUS-FCD-DPPS, median [IQR]
270 [187–455]
22.99 [13.02–45.05]
99 [69–159]
EUS-GE, median [IQR]
349 [268–673]
0.1
43.54 [27.95–88.22]
0.03
201 [146–315]
0.03
Duodenal stent, median [IQR]
342 [217–435]
29.42 [19.42–45.55]
142 [113–203]
EUS-HGS, median [IQR]
1304 [503–1676]
81.24 [49.39–122.74]
286 [218–430]
ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound;
DPPS, double-pigtail plastic stent; FCD, fluid collection drainage; LAMS, lumen apposing
metal stent; SEMS, self-expandable metal stent.
EUS-choledochoduodenostomy, EUS-fluid collection drainage with LAMS and EUS-gallbladder
drainage lie in the lower quartile of RE, whereas EUS-GE, EUS-hepaticogastrostomy
and duodenal stenting lie in the upper one.
Fig. 1 Box-and-whiskers plots of Kerma-Area Products (KAP) values distribution according
to each t-EUS procedure. Different colors represent the lower (green), intermediate
(yellow) and higher (red) quartiles in which median values of KAP for each t-EUS procedure
are distributed. EUS-guided choledocoduodenostomies (EUS-CDS) are further compared
with ERCP with metal SEMS placement as well as EUS-guided Gastroenterostomies (EUS-GE)
are compared with duodenal stent placements (P values shown above the bracket).
There was a significant difference in the median value of Ka,ref , KAP and FT between different t-EUS procedures, with EUS-CDS, EUS-FCD-LAMS and EUS-GBD
being in the lower quartile, EUS-GE and EUS-HGS in the higher quartile, while EUS-FCD-DPPS
showed intermediate exposure (P < 0.000001)
Radiation exposure of t-EUS versus comparators
EUS-CDS had significantly lower KAP than ERCP-SEMS performed for the same indication
(0 [0–0] vs. 25.44 [17.21–54.84] Gy·cm2 , P < 0.0001), because most EUS-CDSs were performed without fluoroscopy. EUS-GE had a
higher KAP than duodenal stenting (43.54 [27.95–88.22] versus 29.42 [19.42–45.55]
cGy·cm2 , P = 0.03), despite the comparable Ka,ref (P = 0.1).
Radiation exposure according to procedure complexity
RE was compared for procedures with intraprocedure troubles (see Supplementary Table 3 for detailed description) versus those without such complications ([Fig. 2 ] and Supplementary Table 3 ).
Fig. 2 Kerma-Area Products (KAP) for each t-EUS procedure, further stratified by procedure
complexity. For each endoscopic procedure, box-and-whiskers plots of values distribution
are separately represented for “trouble-free” procedures in black and procedures with
inconveniences (when any) in orange. P values of comparisons are reported above brackets.
A difference was evident for EUS-CDS, where misdeployments or over-the-wire LAMS placement
for a poorly-dilated duct required a median KAP of 26.62 [0–58.05] Gy·cm2 versus no radioscopy in the complication-free procedures (P = 0.02)
The KAP of complex EUS-GE and EUS-HGS was higher than complication-free procedures,
without reaching statistical significance due to a high basal KAP.
ERCPs with difficult cannulation according to European Society of Gastrointestinal
Endoscopy guidelines [6 ] required higher RE than smooth cannulations (P = 0.045).
Discussion
The International Commission on Radiological Protection recommends the use of procedure-specific
diagnostic reference levels as a tool to analyze and optimize RE for both patients
and physicians, usually obtained collecting RE measures from different health facilities
and using the 75th percentile of median values as reference [2 ]. These values serve to monitor local clinical practice, as for example if RE consistently
exceeds identified references.
Pancreatobiliary endoscopy is the area of gastrointestinal endoscopy in which ionizing
radiation is used the most. The 2012 ESGE Guideline on Radiation Protection underscored
that limited information was available regarding mean KAP values for therapeutic ERCP,
between 8 and 33 Gy·cm2
[7 ]. The guideline also suggested that KAP be recorded in each ERCP report [7 ], even if this practice has not been implemented.
The advent of therapeutic EUS has enormously changed clinical practice in pancreatobiliary
endoscopy units, introducing new possibilities for biliary obstruction, gastric outlet
obstruction, and acute cholecystitis management [1 ]. However, little is known regarding RE for patients and physicians. Whereas EUS
adds endosonographic guidance for accessing a target organ, many procedures involve
technical steps for which radiologic guidance remains fundamental.
One recent prospective multicenter study evaluated RE of 13,000 gastrointestinal procedures
in 23 Japanese hospitals. However, only 374 (2.8 %) were t-EUS procedures, with no
insight on different subtypes [8 ]. The only available publication in this field is a retrospective study comparing
105 t-EUS procedures and 372 ERCPs showing an higher KAP of the former [9 ]. However, all t-EUS procedures were performed with a needle-guidewire-dilation-stent
technique. Conversely, the introduction of LAMS allows one-step and free-hand access
and stent deployment, significantly reducing procedure risks and theoretically allowing
for fluoroless release. Moreover, it has also paved the way for newer procedures,
such as EUS-guided anastomoses.
To the best of our knowledge, no paper describes RE of t-EUS procedures performed
with LAMS, and none describes EUS-GE. Moreover, no paper has compared t-EUS with standard
endoscopic alternatives having the same indication and anatomy.
Our paper found that some t-EUS procedures were mainly performed fluoroless.
Among these, EUS-CDS has an established role in palliation of distal malignant biliary
obstruction when ERCP fails [1 ], so as to be even investigated as an upfront alternative to ERCP, because it has
the potential to reduce the rate of acute pancreatitis [10 ]. In this scenario, a reduced RE might be an additional advantage.
EUS-GBD may be performed fluoroless as well; in our study additional radioscopy was
used for prophylactic coaxial DPPS, and resulted in a very low RE, much lower than
expected for percutaneous cholecystostomy (P-GBD), which is entirely performed under
radioscopic guidance. This adds to the advantages in terms of reduced acute cholecystitis
recurrence [11 ], and the possibility of direct endoscopic cholecystoscopy for stone clearance [12 ].
As for peripancreatic fluid collections, endoscopic drainage is the established initial
treatment modality [13 ], either by DPPS or LAMS. In our study, the latter was mainly performed fluoroless,
while the former required a higher RE to guide the needle-guidewire-cystotome-stent
sequence. While this might appear to be an argument in favor of LAMS, a recent randomized
controlled trial found an increased rate of stent-related complications (mostly bleeding)
in the LAMS group [14 ], and therefore, advantages (i. e. the possibility of endoscopic necrosectomy) must
be weighed against these safety issues. It is our opinion that the two procedures
are to be used for different indications: LAMS for walled-off necrotic collections
whereas DPPS for pseudocysts or “clear” collections [3 ].
In this study, two of the t-EUS procedures had the highest RE. EUS-GE is emerging
as a valuable treatment option for management of gastric outlet obstruction, being
as effective as surgical bypass while having increased clinical success and reduced
long-term dysfunction when compared to duodenal stenting [1 ]
[15 ]. Our study shows that RE of EUS-GE and duodenal stenting seem of the same order
of magnitude, being slightly significantly higher for the former. In our center, fluoroscopy
is mainly needed for oro-jejunal tube placement; we strongly believe that full control
of jejunal distention, the possibility of depicting anatomy with contrast, and the
ability to endosonographically visualize of the tube are key for increasing technical
success [4 ]
[16 ].
Finally, in our study, EUS-HGS had the highest RE among t-EUS procedures. EUS-HGS
involves a multistep sequence for biliary access, cholangiography, duct cannulation,
and tract creation. Millimetric precision is also required for stent placement, the
uncovered part of which must be placed inside the biliary tree, while the covered
part is deployed transhepatically and transgastrically; all these steps must be performed
under real-time radioscopic guidance. However, the alternative to this procedure would
be percutaneous transhepatic biliary drainage, for which comparable RE has been reported
[17 ].
We also compared “trouble-free” procedures with procedures with any inconveniences,
confirming that procedure complexity is a determinant of RE. For example, whereas
most EUS-CDS were performed fluoroless, radioscopy was fundamental in case of stent
misdeployment. This is also in keeping with ESGE indications suggesting that t-EUS
procedures should be performed in a radiology-equipped endoscopic suite, as this might
impact the readiness to solve intraprocedural troubles [18 ].
What clinical consequences could be inferred from these data for everyday practice?
T-EUS procedures are mostly used in the setting of symptom palliation in cancer patients.
Most procedures do not systematically require revision. Finally, most alternatives
require radioscopic guidance as well. For all these reasons, RE of t-EUS is not expected
to represent a major issue from the patient perspective.
Conversely, implications for health care professionals can be inferred. T-EUS expertise
is usually centralized in few referral centers and endoscopists, most of which are
also involved in ERCP. For all these reasons, it might be expected that interventional
endosonographers would have higher exposure to RE. Each health care professionals
involved in radiology-guided procedures usually attends an educational radioprotection
course, is equipped with personal protective equipment such as lead aprons and glasses,
and wears at least two dosimeters, one outside and the other inside the apron [7 ]. Additional measures might be implemented to generally reduce RE. Educational interventions
could be aimed at increasing awareness about how technical settings and beam collimation
influence RE and image quality, especially if technical support for fluoroscopy is
not available. Newer fluoroscopy systems incorporating artificial intelligence-guided
adjustment might further reduce RE to patients and physicians [19 ].
This study has some limitations. First, the retrospective nature might lead to missed
data. However, t-EUS procedures were grouped together under the same label in our
endoscopic reporting system, substantially nullifying this risk. There were some missed
RE measures, but at least FT was available for all cases.
Moreover, the use of fluoroscopy during each procedure might be driven by the experience
of the endoscopist, and therefore, we cannot exclude a role of the learning curve
in influencing RE. However: 1) We included in this study only procedures performed
during the last 3 years; 2) All procedures were performed by three experienced therapeutic
endosonographers, who had completed their training in each procedure before the study
interval; 3) There was no or marginal involvement of trainees in these advanced procedures;
and 4) No significant change in the technical phases and the devices used during each
procedure was made during the study interval. Although some residual effect of increasing
experience might exist, the clearly different values identified for different t-EUS
procedures despite the use of medians and interquartile ranges (marginalizing the
role of outlier values) strongly suggest that the results were driven by the procedures
themselves rather than by other confounders.
Despite all these limitations, this is the first study analyzing RE of t-EUS procedures
performed with modern technologies such as LAMS (the only reporting EUS-GE) and comparing
some of these procedures to standard endoscopic alternatives.
Conclusions
These data should prompt increased awareness of the RE risk among health care professionals
involved in t-EUS, and further educational initiatives to ideally reduce this exposure,
eventually facilitating a personalized surveillance schedule for pancreatobiliary
endoscopists performing both t-EUS and ERCPs. Finally, these RE metrics might provide
an initial indication of diagnostic reference levels, while regulators identify validated
ones for monitoring real-world clinical practice.
