Introduction
Acute pancreatitis (AP) incidence ranges from 4.6 to 100 per 100,000 across European
countries with increasing trends [1]. The rate of hospital mortality associated with the condition is approximately 1 %
[2].
Clinical management of AP still represents a difficult challenge, as patients with
severe disease have a high probability of systemic inflammatory response syndrome
and multiorgan failure (MOF) with or without infection and sepsis, leading to a mortality
rate of 10 % to 15 % [3]. The mortality rate associated with MOF has significantly decreased due to improvement
in Intensive Care Unit technology, so that up to 80 % of residual deaths are linked
to late complications of sepsis [4]. Notably, 10 % to 20 % of AP cases are associated with necrosis of the pancreatic
gland, the peripancreatic tissue, or both: this subset of patients may face a complex,
prolonged clinical course, with associated mortality of up to 20 % to 30 % when infection
develops in fluid collections [5].
In 2012, an international consensus revised AP classification and new definitions
of local complications were released. The new classification supported more specific
recommendations about use of drainage: walled-off necrosis (WON) and pseudocysts were
the two pancreatic fluid collections eligible for this treatment [6]
[7]. Both have a well-defined wall, but pseudocysts only contain liquid, whereas WON
holds infected necrotic material.
Recently endoscopic drainage has evolved from use of surgical to percutaneous drainage,
which has equal efficacy with fewer complications and shorter hospital length of stay
[8]
[9]. The classical approach exploits endoscopic ultrasound (EUS) guidance to identify
the collection to drain. This technique is limited by the narrow field of view offered
by EUS imaging. Thus, once the collection is identified, it is difficult to single
out the best position to place the device, hypothetically allowing for the most efficient
drainage. Given that endoscopic drainage also accounts for a non-negligible complication
rate [10], reducing drainage time and the rate of post-drainage complications is an unmet
health care need in patients with pancreatitis. Increasing the accuracy of anatomic
knowledge about PFC might be a way to reduce the risk of complications and to improve
drainage.
Radiology provides fundamental support for operative procedures in digestive endoscopy.
In recent years, technologies in this field have evolved considerably with the development
of hybrid operating rooms (HORs). Among advanced technologies available in modern
HORs, fusion imaging consists of overlaying clinical information from preoperative
computed tomography (CT)/magnetic resonance imaging (MRI) work-up, or per-operative
Cone Beam CT to augment live fluoroscopy, providing a continuous 3 D/2 D overlay for
augmented live guidance [11]
[12]
[13].
These technologies have widely been applied in vascular surgery [13]
[14]: during complex intravascular and percutaneous procedures, fusion imaging has demonstrated
a significant reduction in radiation exposure, duration of procedures, dosage of injected
contrast medium, and provided benefits in clinical outcomes [16]
[17]
[18].
Initial experiences in gastroenterology have also been described integrating preoperative
MRI and CT with ultrasound (US) [19]
[20] – one of these just for PFC drainage – but also with EUS [21], improving the accuracy in defining the anatomical field of intervention and allowing
for more precise maneuvers.
In this paper, we describe a new original fusion imaging and augmented fluoroscopy
technique that we have been using forour biliopancreatic endoscopy procedures following
the installation of a new HOR at our institution in 2017 (Discovery IGS 740 OR, GE
Healthcare).
This retrospective study aimed to assess the potential benefits of this new technique
in terms of clinical and procedural outcomes of EUS-guided drainage of PFC.
Patients and methods
Patients
Among the patients admitted to our hospital from January 2012 to December 2019 for
moderate and severe AP, those who had one or more PFCs eligible for endoscopic drainage
according to the existing guidelines were included in the study. Diagnosis of moderate
and severe AP, PFC, and WON was based on the revised standards from Atlanta [6]. The first set of consecutive patients (17 patients, over the period 2012–2017)
received the standard EUS approach whereas the last set of consecutive patients (18
patients, over the period 2017–2019) were treated with the “fusion imaging” approach.
Informed consent for the interventional procedures was obtained from each patient.
Data were collected and analyzed retrospectively. This study was approved by the Ethics
Committee of Area Vasta Emilia Nord of the Emilia Romagna Regional Health System (protocol
number 2020 /0089372). Patients were asked to sign written informed consent. For patients
who were not reachable at the time of the retrospective study, the Ethics Committee
authorized the use of patient data without their informed consent if all reasonable
efforts had been made to contact them to them and acquire their consent.
Patient characteristics including age, pancreatitis etiology, collection site, type
of collection, baseline size on work-up imaging, indication for drainage, time to
drainage from pancreatitis onset, and maximum follow-up time after the procedure are
reported for both groups.
Treatment
Equipment and materials: “fusion imaging” technique
Patients arriving at the Reggio Emilia hospital from February 2012 to April 2017 and
needing a PFC drainage received standard EUS guidance combined with a traditional
surgical mobile C-arm (OEC 9800 Plus, GE Healthcare, Chicago, Illinois, United States).
Patients arriving from June 2017 to December 2019 were treated in a modern HOR suite
equipped with advanced fusion imaging, using Discovery IGS 740 OR. In the fusion imaging
group, the following operative sequence was adopted ([Fig. 1]):
-
Manual segmentation of the PFC was performed based on the pre-procedural CT.
-
The resultant region of interest was placed on the volume rendering, a volumetric
reconstruction algorithm that allows three-dimensional visualization of the skeleton
[22];
-
The volume including PFC and bone was superimposed onto live fluoroscopy (ASSIST software,
GE Healthcare). Registration between the preoperative volume and the live fluoroscopy
was performed on two orthogonal fluoroscopy projections using anatomical landmarks
(such as vertebrae and iliac crest) or “proxy” landmarks (clips, stents, etc.). Once
registered in these two views, PFC volume from the preoperative CT remained fused
to intraprocedural fluoroscopy for every image acquisition, showing the real-time
scope tip relative to the whole PFC shape, thus supporting the choice of puncture
site. Fusion imaging remained automatically registered with Gantry and Table motion,
allowing for augmented fluoroscopy with flexible system setup.
Fig. 1 The three steps in the fusion imaging procedure before draining pancreatic fluid
collections.
Equipment and materials: endoscopic drainage
All procedures were performed under general anesthesia by endoscopists with over 5
years of experience in interventional endosonography (R.S., L.C., P.C., V.I.). A linear
therapeutic echo‐endoscope was used in combination with fluoroscopy.
The presence and location of vessels were assessed by means of color Doppler ultrasonography
to determine the optimal transmural puncture (gastric or duodenal) site on the cyst.
Under real‐time EUS and fluoroscopy guidance, a 19-gauge access needle (Cook Medical,
Limerick, Ireland) was used to puncture the PFC, whose shape was subsequently outlined
– especially in patients treated with standard EUS – by contrast medium. After a 400-cm,
0.035-inch guidewire (Visiglide, Olympus) had been introduced and coiled into the
cyst cavity, the needle was removed.
Subsequently, a cysto-gastrostomy was made using a 10F cystogastrostome (Cook medical,
Limerick, Ireland) and dilated as needed using a balloon dilator (QBD‐6 × 3, Cook
Medical) in order to make the insertion of double pigtail plastic stents (PS) (7F
or 10F, Cook Medical) or fully covered self-expandable metal stents (FCSEMS) (Taewoongh
Niti-S) easier. In the case of lumen-apposing metal stents (LAMS) (Hot Axios, Boston
Scientific), the stent was directly positioned after the guidewire placement. Moreover,
a nasocystic tube (7F or 10F, ENBD‐7‐LIGUORY‐C, Cook Medical) was inserted into the
cavity for lavage. Endoscopic retrograde cholangiopancreatography was not routinely
performed before transmural drainage.
Necrosectomy
After the initial procedure, the endoscopist determined whether an endoscopic necrosectomy
– direct (DEN) or to be performed in a subsequent endoscopic session – was required
depending on the patient’s condition and whether the pre-procedural imaging showed
remarkable solid debris. When performed, it was usually carried out using snares,
retrieval nets or Dormia baskets as appropriate and hydrogen peroxide 3 % (1:10 saline
solution) infusions.
Baseline and follow-up radiologic imaging
For each patient with PFC, radiological work-up was performed by following the same
method (CT or MRI, according to clinical indication) at baseline (before the endoscopic
procedure) and at follow-up. PFC evolution was assessed according to clinical indication
either in an outpatient clinic or in local hospitals, at 2 weeks and 6 to 8 weeks
after first stent placement on average, and until complete resolution or at the last
available follow-up.
All patients, except those who died or were lost of follow‐up, were monitored for
at least 3 months up to a maximum of 43 months.
CT scans were performed by means of a 64– or a 128-multidetector scanner, while MRI
exams were performed with a 1.5 T scanner. PFC volume identified by both methods was
retrospectively calculated at baseline and during follow-up examinations by a single
radiologist blinded to baseline clinical condition and type of endoscopic procedure,
by using a manual segmentation method similar to that described for fusion imaging.
Examples of baseline and follow-up radiological images of PFC patients are reported
in [Fig. 2] and [Fig. 3].
Fig. 2 a Axial and b coronal portal venous phase CT scan showed a fluid collection containing gas and
demonstrating enhancing walls (arrows). c This walled-off necrosis was manually segmented for our analysis, resulting in a
volume of 147 mL. Three months after drainage performed using traditional guidance
(Group 1), a small residual collection was still visible in d axial and sagittal e portal venous phase CT scan (arrows), it had a volume of 12 mL.
Fig. 3 a Axial and b sagittal portal venous phase CT scan showed a fluid collection with a volume of 523 mL
and with enhancing walls strictly adherent to the gastric wall (arrows). c This collection was manually segmented and d overlaid to augment live fluoroscopy. e During this procedure, contrast media was also injected in the collection to verify
its consistency. One month after stent positioning, a very small residual collection
was visible in f axial portal venous phase CT scan (arrows), with a residual volume < 2 mL. g Three months after, a coronal T2-weighted MR scan showed only fibrosis without residual
fluid collection (arrow).
Endoscopic follow-Up
Stents were removed using standard endoscopic snares or rat‐tooth forceps based on
the type of stent, FCSEMS or LAMS (for the latter a stricter indication for early
removal exists). When drainage was not complete subsequent plastic stents were placed.
Study outcomes
We aimed to assess the differences in procedural and clinical outcomes between the
traditional EUS approach and the fusion imaging advanced guidance.
Our primary outcome was overall treatment success rate, defined as both clinically
significant improvement in patient symptoms and complete resolution (complete emptying)
of PFC. Complete resolution of PFC was considered on follow-up imaging for non-measurable
residual collections < 10 mL in volume (e. g. adipose tissue stranding with fibrotic
strands and possibly minimal free fluid, without walls).
Secondary outcomes included technical success rate, time to resolution, hospital stay
length, adverse events (AEs), and recurrence rate. Technical success was defined as
successful transmural stent placement. Time to resolution was determined as the time
needed to reach complete emptying, from endoscopic drainage. AEs were classified according
to the American Society of Gastrointestinal Endoscopy (ASGE) guidelines [22]. Major AEs included events that required surgery, interventional treatments (such
as endoscopic, percutaneous and vascular treatment) or transfusion, or those inducing
death.
Length of hospital stay was defined as the time from initial stent placement to hospital
discharge. Recurrence was defined as the presence of a PFC > 3 cm3 in size discovered after its initial complete resolution, by assessing the imaging
obtained up to the last available follow-up date.
We reported procedural differences as well, including use of a nasocystic tube, the
type of stent used, access site, use of iodate contrast medium, presence of stent
obstruction, procedure time, time to stent removal, and need for reintervention or
necrosectomy. Procedure time was determined as duration of the intervention from insertion
to withdrawal of the endoscope. Reintervention was defined as need to repeat an endoscopic
intervention for AEs or insufficient drainage (including endoscopic necrosectomies).
Notably, planned stent changes and stent removals were not counted as reintervention
Statistical analyses
Continuous variables (age, baseline size, follow-up times, procedure time, hospital
stay length) are reported as median (IQR) and mean (SD). Categorical variables are
reported as proportions.
To compare variables between two groups, as well as to assess the impact of the stents
used, the Fisher exact test was used for categorical variables, and the median test
was used for continuous variables.
Analyses were conducted on a per-PFCs basis while taking into account the intra-individual
correlation to obtain robust variance estimates with SVY command on STATA/IC version
16. Odds ratios (OR) with 95 % confidence intervals (95 % CI) for overall treatment
success were estimated using a logistic regression model. For the main outcome, we
applied a multivariable model, adjusted for known prognostic factors that were upstream
the procedure in the causal pathway, i. e. age (< 45, 45–65, > 65), baseline size
(cm3) and type of collection (pseudocyst, WON). We did not include in the model variables
that could be linked to the procedure itself to avoid adjusting for potential mediators,
i. e. type of stent, site of stent placement, necrosectomy. To exclude that, the association
between outcome and fusion imaging was exclusively due to introduction of the Axios
stent or to the presence of necrosectomy – two characteristics that were almost exclusively
present in the period when fusion imaging was introduced – we present the association
between the type of stent and necrosectomy and outcome in the supplementary materials.
No significance threshold was fixed; P values were interpreted as continuous variables.
Results
General data
From 2012 to 2019, 437 patients were admitted to our center for severe and moderately
severe AP. Among them, 38 patients had PFCs amenable to endoscopic drainage, but three
of them were excluded from our analysis: two patients had mucinous cystadenoma and
serous cystadenoma at subsequent diagnostic investigations; one was a postsurgical
collection in a patient with pancreatitis. Of 34 patients with 35 PFCs ultimately
included in the study, the first 17 consecutive were treated with the traditional
approach while the latter 18 were offered the fusion imaging guidance technology.
Patient characteristics and comparison of the prognostic factors
Patient characteristics are listed in [Table 1]. The two groups had very similar age and sex distribution and the pathogenesis of
pancreatitis was similarly distributed. The groups differed in terms of baseline size
and typology of pancreatic fluid collections: patients treated with fusion imaging
had larger PFCs (570.0 vs 263.9 cm3, n.s.) mostly WON (P = 0.041) than those treated drainage with EUS. Moreover, obstructive symptoms (gastric
outlet obstructive syndrome, pain, jaundice) were the prevalent indication for drainage
in those treated with standard EUS, while patients treated with fusion imaging required
earlier treatment (40 vs. 115 days from pancreatitis onset, P = 0.007) for PFC infection and its systemic implications. One patient treated with
fusion imaging had previously been treated with percutaneous US-guided drainage as
well, and the poor result led to attempting the endoscopic route.
Table 1
Clinical characteristics of the included patients as a whole population, and subdivided
in to two groups.
|
Baseline characteristics
|
|
Total
|
Standard EUS
|
Fusion imaging
|
|
|
N
|
N (% col)
|
N (% col)
|
P[1]
|
|
Total no. patients
|
35
|
17
|
18
|
|
|
Male sex
|
27 (77.7)
|
13 (76.5)
|
14 (77.7)
|
0.57
|
|
Age (years)
|
|
median (IQR)
|
57 (47–68)
|
49 (44–67)
|
60 (52–78)
|
0.39[2]
|
|
Pancreatitis
|
0.43
|
|
|
11 (31.4)
|
6 (35.3)
|
5 (27.8)
|
|
|
11 (31.4)
|
4 (23.5)
|
7 (38.9)
|
|
|
1 (2.9)
|
1 (5.9)
|
0 (0)
|
|
|
6 (17.1)
|
2 (11.8)
|
4 (22.2)
|
|
|
1 (2.9)
|
0 (0)
|
1 (5.6)
|
|
|
5 (14.3)
|
4 (23.5)
|
1 (5.6)
|
|
Kind of collection
|
0.04
|
|
|
20 (57.1)
|
13 (76.5)
|
7 (38.9)
|
|
|
15 (42.9)
|
4 (23.5)
|
11 (61.1)
|
|
Collection site
|
|
|
|
32
|
14
|
18
|
|
|
8
|
6
|
2
|
|
|
3
|
0
|
3
|
|
|
6
|
3
|
3
|
|
Baseline size (cm3)
|
|
median (IQR)
|
417.8 (153.9–785.4)
|
263.9 (130.9–586.4)
|
570.0 (257–857.7)
|
0.13[2]
|
|
Baseline size (cm3)
|
0.16
|
|
|
4 (11.4)
|
4 (23.5)
|
0 (0)
|
|
|
14 (40)
|
7 (41.2)
|
7 (38.9)
|
|
|
12 (34.3)
|
4 (23.5)
|
8 (44.4)
|
|
|
5 (14.3)
|
2 (11.8)
|
3 (16.7)
|
|
Reason for drainage
|
0.08
|
|
|
12 (34.3)
|
8 (47.1)
|
4 (22.2)
|
|
|
6 (17.1)
|
2 (11.8)
|
4 (22.2)
|
|
|
7 (20.0)
|
5 (29.3)
|
2 (11.1)
|
|
|
10 (28.6)
|
2 (11.8)
|
8 (44.4)
|
|
Drainage after (days)
|
|
|
45 (30–96)
|
115 (62–315)
|
40 (25–60)
|
0.007
|
|
Maximum follow-up (days)
|
|
|
76 (50–240)
|
170 (43.5–240)
|
55.5 (50–72)
|
0.03
|
Clinical characteristics of the included patients as a whole population, and subdivided
into two groups.
EUS, endoscopic ultrasound; ERCP, endoscopic retrograde cholangiopancreatography;
WON, walled-off necrosis; GOOS, gastric outlet obstruction syndrome; IQR, interquartile
range.
1 Fisher's exact test.
2 Median test. Values are reported as number (%) unless otherwise indicated.
Effectiveness outcomes
Clinical and procedural outcomes are reported in [Table 2]. There was no difference in terms of technical success between the two groups: the
stent was placed in all cases. Symptom improvement was 88.9 % with fusion imaging
and 76.5 % with standard EUS (P = 0.539) and complete emptying rates were 83.3 % and 64.7 %, respectively (P = 0.264). When combining the two outcomes in the overall treatment success rate,
the difference was more evident (83.3 % vs. 52.9 %, P = 0.075), corresponding to a failure rate that was three times lower. Regarding time
to complete emptying, 11 PFCs treated under fusion imaging guidance achieved resolution
within 90 days (61.1 %), while four PFCs did (23.6 %) among those treated with EUS.
Table 2
Procedural results for the included patients as a whole population, and subdivided
into two groups.
|
Effectiveness outcomes
|
|
|
|
|
|
Tot
|
Standard EUS
|
Fusion imaging
|
|
|
N
|
N (% col)
|
N (% col)
|
P[1]
|
|
Total number of patients
|
35
|
17
|
18
|
|
|
Symptom improvement
|
0.54
|
|
|
29 (82.9)
|
13 (76.4)
|
16 (88.8)
|
|
|
3 (8.6)
|
2 (11.8)
|
1 (5.6)
|
|
|
3 (8.6)
|
2 (11.8)
|
1 (5.6)
|
|
Complete emptying
|
0.26
|
|
|
9 (25.7)
|
6 (35.3)
|
3 (16.7)
|
|
|
26 (74.3)
|
11 (64.7)
|
15 (83.3)
|
|
Overall treatment success
|
0.075
|
|
|
11 (31.4)
|
8 (47.1)
|
3 (16.7)
|
|
|
24 (68.6)
|
9 (52.9)
|
15 (83.3)
|
|
Time for complete emptying (days)
|
0.15
|
|
|
9 (25.7)
|
3 (17.7)
|
6 (33.3)
|
|
|
6 (17.2)
|
1 (5.9)
|
5 (27.8)
|
|
|
11 (31.4)
|
7 (41.2)
|
4 (22.2)
|
|
|
9 (25.7)
|
6 (35.3)
|
3 (16.7)
|
|
Complications
|
0.29
|
|
|
24 (68.6)
|
11 (64.7)
|
14 (73.8)
|
|
|
11 (31.4)
|
6 (35.3)
|
4 (22.2)
|
|
Death
|
0.60
|
|
|
32 (91.4)
|
15 (88.2)
|
17 (94.4)
|
|
|
3 (8.6)
|
2 (11.8)
|
1 (5.6)
|
|
Hospital stay (days)
|
|
|
10 (7–28)
|
7 (6–10)
|
26 (9–30)
|
0.006[2]
|
|
|
19.7 ± 27.3
|
8.2 ± 4.3
|
29.1 ± 34.4
|
EUS, endoscopic ultrasound; SD, standard deviation; IQR, interquartile range.
1 Fisher's exact test.
2 Median test. Values are reported as number (%) unless otherwise indicated.
The logistic regression model adjusted for age, baseline PFC volume, and kind of collection
confirmed the direction of the association with a higher overall treatment success
rate with fusion imaging (OR = 5.28; 95 % CI = 0.79–35.51), even if this association
may be due to random fluctuations ([Table 3]).
Table 3
Logistic regression model for overall treatment success, defined as significant improvement
in patient symptoms and complete resolution (complete emptying) of PFC.
|
OR
|
95 % CI
|
P value
|
|
Age
|
|
|
1
|
|
|
|
|
0.64
|
0.06–6.96
|
0.704
|
|
|
0.25
|
0.02–2.91
|
0.260
|
|
Baseline PFC Volume (for 1 cm3 increase)
|
1.00
|
1.00–1.00
|
0.342
|
|
Kind of collection
|
|
|
1
|
|
|
|
|
0.99
|
0.16–6.15
|
0.995
|
|
Group
|
|
|
1
|
|
|
|
|
5.28
|
0.79–35.51
|
0.085
|
Covariates selected as clinically relevant were: age, baseline PFC volume, kind of
collection and patient group, odds ratio, confidence interval, pancreatic fluid collection,
and wall-off necrosis.
PFC, pancreatic fluid collection; OR, odds ratio; CI, confidence interval; WON, walled-off
necrosis; EUS, endoscopic ultrasound.
Among those treated with standard EUS, the following AEs were observed: three sepsis
(fever + positive hemoculture), one intraprocedural bleeding, one spleno-mesenteric
thrombosis, and one stent buried in the gastric wall. Among those treated under fusion
imaging guidance, two gastric perforations by plastic stents and two massive bleedings
of the splenic artery were reported. Overall, six were major AEs requiring endoscopic
management (with hemostatic maneuvers or stent removal) or radiological embolization,
with equal distribution between the two groups; four were treated conservatively with
medical therapy (antibiotics and anticoagulants). Although these complications are
connected with the endoscopic procedure, some of them could be considered stent-related
complications (bleeding, incystment and perforation).
Hospital stay was longer for those treated under fusion imaging guidance compared
with those who received standard EUS (median 26 vs 7 days, P = 0.006).
One patient per group had recurrence after resolution: as both were asymptomatic,
they are still being followed radiologically and clinically.
Procedural differences
Procedural differences are reported in [Table 4]. Iodate contrast medium was used in 82.4 % of standard EUS cases versus 33.3 % in
cases treated with fusion imaging (P = 0.006). In particular, contrast injected after puncture was used in most standard
EUS procedures to confirm the puncture site and outline the collection shape. However,
this post-contrast X-ray acquisition is late and operatively useless because it is
only available after the puncture site has already been chosen and the cysto-gastric
tract has consequently been created. Conversely, fusion imaging allowed PFC visualization
before puncture, so contrast was rarely used in cases treated under fusion imaging
guidance. In the few cases contrast was used, it was to assess alignment between the
virtual PFC volume and the real PFC during the first drainages performed with the
new technology.
Table 4
Procedural characteristics of the included patients as a whole population, and subdivided
in to two groups, to underscore potential procedural differences among groups.
|
Total
|
Standard EUS
|
Fusion imaging
|
|
|
N
|
N (% col)
|
N (% col)
|
P[1]
|
|
Total no. patients
|
35
|
17
|
18
|
|
|
Endoscopic sessions
|
0.31
|
|
|
13 (37.1)
|
8 (47.1)
|
5 (27.8)
|
|
|
22 (62.9)
|
9 (52.9)
|
13 (72.2)
|
|
Nasocystic tube
|
1.000
|
|
|
7 (20.0)
|
3 (17.7)
|
4 (22.2)
|
|
|
28 (80.0)
|
14 (82.4)
|
14 (77.8)
|
|
Type of stent (first)
|
0.001
|
|
|
1 (2.9)
|
1 (5.9)
|
0 (0)
|
|
|
14 (40)
|
11 (64.7)
|
3 (16.7)
|
|
|
19 (54.2)
|
4 (23.5)
|
15 (83.3)
|
|
|
1 (2.9)
|
1 (5.9)
|
0 (0)
|
|
Type of stent (second)
|
0.15
|
|
|
23 (65.7)
|
13 (76.4)
|
10 (55.6)
|
|
|
11 (31.4)
|
3 (17.7)
|
8 (44.4)
|
|
|
1 (2.9)
|
1 (5.9)
|
0 (0)
|
|
Access
|
0.48
|
|
|
27 (79.4)
|
15 (88.2)
|
13 (72.2)
|
|
|
2 (5.9)
|
0 (0)
|
2 (11.1)
|
|
|
5 (14.7)
|
2 (11.8)
|
3 (16.7)
|
|
Contrast medium
|
0.006
|
|
|
15 (42.9)
|
3 (17.7)
|
12 (66.7)
|
|
|
20 (57.1)
|
14 (82.4)
|
6 (33.3)
|
|
Stent obstruction
|
0.40
|
|
|
28 (80)
|
15 (88.2)
|
13 (72.2)
|
|
|
7 (20)
|
2 (11.8)
|
5 (27.8)
|
|
Stent removal after (days)
|
0.0001[2]
|
|
|
35.5 (27–60)
|
120 (50–170)
|
30 (26–37)
|
|
|
58.3 ± 50.7
|
106.7 ± 60.4
|
32.8 ± 13.5
|
|
Necrosectomy
|
0.008
|
|
|
28 (80.0)
|
17 (100)
|
11 (61.1)
|
|
|
7 (20.0)
|
0 (0)
|
7 (38.9)
|
|
|
1
|
|
1 (14.3)
|
|
|
6
|
|
6 (85.7)
|
|
|
5
|
|
5 (71.5)
|
|
|
2
|
|
2 (28.5)
|
|
Reintervention
|
0.18
|
|
|
16 (45.7)
|
10 (58.8)
|
6 (33.3)
|
|
|
10 (28.6)
|
5 (29.4)
|
5 (27.8)
|
|
|
9 (25.7)
|
2 (11.8)
|
7 (38.9)
|
|
Reintervention rate
|
54 %
|
41 %
|
67 %
|
|
Procedure time (minutes)
|
|
|
80 (55–100)
|
95 (60–145)
|
73 (45–92)
|
0.39[2]
|
|
|
84.1 ± 39.1
|
99.7 ± 43.9
|
69.4 ± 27.8
|
Values are reported as number (%) unless otherwise indicated.
EUS, endoscopic ultrasound; FCSEMS, fully covered self-expandable metal stents; IQR,
interquartile range; SD, standard deviation.
1 Fisher's exact test.
2 Median test.
PFCs treated under fusion imaging guidance were drained predominantly with Axios stents
(83.3 %), introduced in our center in 2015, whereas FCSEMS were the most used stents
in standard EUS (64.7 %). Procedure time was reduced with fusion imaging compared
with standard EUS (69.4 vs. 99.7 minutes, P = 0.033).
On average, first stent removal was scheduled and performed earlier in patients treated
under fusion imaging guidance compared to standard EUS (32.8 vs 106.7 days, P = 0.0001). This is most likely because of the higher use of Axios stents. In four
of 16 subjects treated with standard EUS and eight of 18 subjects with fusion imaging
(P = 0.15), the first stent was substituted with another to carry on with the drainage.
Reintervention was necessary in 41 % and 67 % of patients treated with standard EUS
and fusion imaging, respectively (P = 0.18), due not to controlled ongoing sepsis or persistency of the pancreatic fluid
collection volume or failure to improve symptoms. Among reinterventions, endoscopic
necrosectomy was performed exclusively over the second period of time, i. e. when
fusion imaging was adopted, in seven of 18 patients; only one was DEN whereas the
other cases were executed in subsequent sessions after stent placement.
To evaluate whether the aforementioned difference in treatment success in favor of
fusion imaging could be due to the impact of Axios stents and necrosectomies, we compared
the results obtained with Axios stents and non-Axios stents stratified for standard
EUS and fusion imaging (Supplementary Table 1), and with necrosectomy and without necrosectomy in patients treated with fusion
imaging, because there is no necrosectomy in the standard EUS (Supplementary Table 2). Success rates were almost identical in the results with Axios and non-Axios stents,
while a longer median time to removal in the non-Axios group was only observed (120
vs. 50 days, P = 0.45) for standard EUS – this is likely due to the strict indication to remove
Axios stents within 3–4 weeks – in fusion imaging patients, the median time to removal
between Axios and not-Axios stents was the same. Only seven patients underwent a necrosectomy
and they were all during the period when fusion imaging was adopted. Overall success
rate was almost identical in patients with and without necrosectomy, while time to
complete emptying and hospital stay were longer in patients with necrosectomy.
Discussion
In the present case series, introduction of a new original approach combining augmented
fluoroscopy with EUS in a HOR was associated with a simultaneous improvement in clinical
success rate and shorter time to complete emptying of the PFC. The study design did
not permit us to assess whether these associations were causal or if other changes
that occurred concomitantly in the case mix or in the procedures confounded our results.
Nevertheless, it is worth noting that although patients treated during the second
period of time, when fusion imaging guidance was adopted, required earlier intervention
for larger, more complex and often infected collections compared to patients treated
with standard EUS, the clinical treatment failure rate was about three times lower
and complete emptying within 90 days almost doubled. These estimates are rather imprecise
and differences may be due to chance, but if they were confirmed, it would be a clinically
relevant improvement. On the other hand, it must be considered that in the period
of time when fusion imaging was adopted, hospital length of stay was longer, particularly
in cases undergoing necrosectomy, and this was only the case over this time period
and it was not true when standard EUS was used.
In our experience, endoscopists perceived that augmenting live fluoroscopy guidance
with the PFC anatomy volume from preoperative CT was helpful in identifying the optimal
drainage point relative to the anatomy of the PFC, particularly for complex and multiloculated
collections. Augmentation of the operating field with a virtual model of the collection
compensated for EUS’s limited field of view in the choice of this drainage point.
In our center, we used to inject contrast medium to obtain better control of site
puncture and to identify the collection’s shape, before placing FCSEMS, LAMS, and
plastic stents. Fusion imaging helped us to avoid use of contrast. In fact, in the
few cases in which we decided to inject contrast medium to assess the technology,
the virtual volume observed with fusion imaging showed excellent consistency and alignment
accuracy with the real collection ([Fig. 4]). Minimal distortion was observed due to endoscope introduction and insufflation.
In addition, it is known that injection of iodinated contrast medium within closed
cavities like a PFC increases the risk of infection [23], which has been the prevalent complication in patients treated with traditional
guidance. Therefore, less use of contrast media after the introduction of fusion imaging
might be responsible for the reduction in AEs in patients treated under fusion imaging
guidance.
Fig. 4 Augmented fluoroscopy overlaying a virtual PFC volume from the pre-operative CT to
the live fluoroscopy. The iodinated contrast infused in the PFC reveals great alignment
of the virtual PFC volume with live fluoroscopy.
In addition to reducing contrast utilization, procedure time was about 20 minutes
shorter with fusion imaging than with standard EUS. Fusion imaging required additional
preparation time for CT segmentation and alignment on fluoroscopy, which was not measured
in this study. However, in our experience, this time was of about 10 minutes, with
the total procedure time thus still decreasing with use of the new approach. Despite
the fact that this difference was possibly due to chance, it is also consistent with
an increase in endoscopist confidence in the puncture maneuver. Furthermore, although
not quantified in this study, associated benefits in terms of patient and operator
radiation exposure are foreseen and warrant further investigation.
The evident limitations of the study include limited sample size and the heterogeneity
of the two groups in terms of size and typology of lesions and clinical indication
for drainage. However, while prognostic factors should have worked in favor of the
standard EUS guidance group, a better clinical success rate was observed in the fusion
imaging group. The increased complexity in the treated cases is the consequence of
the progressive increase in indications for PFC drainage applied in our center, in
accordance with changes in international guidelines [24]. Furthermore, other procedural features of the intervention changed during the study
period. In particular, in the fusion group, the use of LAMS Axios was more systematic,
but our analysis suggests that this change had little or no impact on outcomes and
cannot explain the differences observed between the two groups. Also, the execution
of necrosectomy only occurred in cases treated in the second study period, because
it was actually feasible only after positioning LAMS, and it was deemed necessary
because of patient critical clinical situations, linked to the infection of WON, which
was also more prevalent in the second study period. In addition, this difference cannot
explain the higher success rate in the second study period, because necrosectomy was
not associated with the success rate, while it was inversely associated with time
to complete emptying and hospital length of stay. In particular for this latter outcome,
the median time in patients without necrosectomy was very similar in the two study
periods (Supplementary Table 2), suggesting that the observed negative association between hospital length of stay
and fusion imaging was partially due to the difference in the proportion of patients
needing necrosectomy. Finally, drainage was assessed exclusively with CT and MRI scans,
with the usual (and variable) timing of clinical follow-up in these patients and not
according to fixed timing for follow-up. Also, the clinical outcome assessment was
not blinded to the intervention group, thus, assessment bias could be present. To
reduce this bias, assessment of drainage through imaging was conducted retrospectively
by a radiologist who was blinded to the group.
Conclusions
Use of radiology to support endoscopic treatment is constantly evolving, with the
goal of more effective and safer therapies with a limited number of treatments. The
new technique we propose is not so difficult to implement in clinical practice. However,
it requires use of a modern HOR equipped with fusion imaging, which is certainly not
widespread in gastroenterology facilities, but often may be available in hospitals
for use by physicians in other specialties.
Despite the study’s limitations, the results suggest that use of fusion imaging and
augmented fluoroscopy in HORs might reduce the time necessary for PFC drainage and
improve clinical success rates. It must be noted that some other outcomes, such as
hospital length of stay and reintervention rate, went in the opposite direction. Future
research should be conducted to explore use of this advanced guidance in larger and
more homogeneous patient series.
