Introduction
Pancreaticobiliary endoscopic ultrasound (PB-EUS) has an established role in the assessment,
staging, and sampling (via EUS-guided fine-needle aspiration [FNA] or biopsy [FNB])
of pancreaticobiliary disease, and increasingly, EUS-guided interventions such as
the drainage of pancreatic fluid collections [1]
[2]. Over the last 10 years, EUS-FNA/FNB has become the standard modality for sampling
solid and cystic pancreatic lesions. There is extensive literature on its diagnostic
performance in solid and cystic disease of the pancreas [3]
[4]
[5]
[6]
[7]. The morbidity and mortality from EUS-FNA/FNB in solid pancreatic lesions is reported
to be 2.4 % and 0.02 %, respectively [8] and in cystic pancreatic lesions 2.7 % and 0.2 %, respectively [9].
However, there are no large, long-term prospective studies of outcomes following PB-EUS
and the impact of procedural and non-procedural factors. In the absence of such prospective
data, population-level observational studies offer the potential to understand PB-EUS
practice and the risk of adverse events associated with EUS and EUS-FNA. There have
been few such studies to date. A recent US study utilizing the Surveillance, Epidemiology,
and End Results (SEER) database addressed concerns about peritoneal seeding following
EUS-FNA for pancreatic cancer and reported no adverse effect of prior EUS-FNA on pancreatic
cancer survival [10]. EUS assessment has been reported to be an independent predictor of improved survival
in locoregional pancreatic cancer through the improved stage-appropriate management
consequent on EUS [10]
[11].
We have examined national changes in the use of EUS and EUS-FNA, to try and identify
the factors contributing to adverse events (AEs) and 30-day mortality after EUS. We
have separately studied subjects with pancreatic cancer who underwent PB-EUS to understand
the factors associated with surgical resection, chemotherapy, and not receiving any
active treatment.
Patients and methods
Data source
Administrative data on all care episodes taking place in National Health Service (NHS)
hospitals in England are recorded in the Hospital Episode Statistics (HES) database.
Unique identifiers track subjects through inpatient and outpatient attendances. Every
recorded episode contains clinical information about diagnoses and procedures, demographic,
administrative, and geographical information. Diagnostic data are coded using the
International Classification of Diseases version 10 (ICD-10) and procedures coded
using the Office of Population Censuses and Surveys Classification of Interventions
and Procedures 4th revision (OPCS-4). HES is linked to the Office of National Statistics mortality data,
providing information on the date and cause of death [12].
Inclusion criteria
All adults over age 18 years undergoing PB-EUS, both as inpatients and outpatients,
in England over 10 years (2007–2016) were included in the study. Subjects diagnosed
with pancreatic cancer by any means within the 6 months following PB-EUS were included
in the PB-EUS pancreatic cancer cohort. Diagnostic data were obtained from ICD-10
coding and procedure data were obtained from OPCS-4 coding (Appendix 1).
Exclusion criteria
Subjects were excluded if they were under age 18 years, resided outside England, or
had incomplete demographic data. EUS procedures for non-PB indications were also excluded
from the study.
Data validation
To assess the validity of coding for PB-EUS, a list of subjects coded for all EUS,
specifically PB-EUS and FNA procedures, was provided by the local coding departments
at Sandwell and West Birmingham NHS Trust, Newcastle upon Tyne Hospitals NHS Foundations
Trust and University Hospitals Birmingham NHS Foundation Trust. These data were used
to match the number of PB-EUS procedures extracted from the HES database for each
individual site. A sample of patient records from all three sites were analyzed by
the research team to establish the accuracy of procedural coding only, but not any
other clinical details, to establish if the procedure coding was consistent with the
clinical records.
Demographic data
Demographic data including age, sex, ethnicity, and deprivation were extracted from
hospital admission coding. Age was considered a continuous variable. Ethnicity was
classified into White, South Asian, Black, mixed ethnicity, and other minority ethnicities.
Deprivation was calculated using an aggregate score for English Lower Layer Super
Output Areas, based on employment status, income, crime levels, and living environment
[13]. Deprivation was categorized by quintiles, with 1 being the most deprived and 5
being the least deprived.
A modified Charlson comorbidity score was calculated using ICD-10 codes for secondary
diagnoses, excluding any form of cancer or diabetes mellitus. The Charlson comorbidity
score has previously been validated in HES [14].
Healthcare providers
PB-EUS providers were stratified based on their number of procedures over the 10 years
study period. Centers with ultra-low volume of PB-EUS activity (< 10 procedures over
the 10-year study period) were excluded. Health care providers were grouped into tertiles
and the range of the number of procedures in each tertile was the natural consequence
of having an equal number of centers in each tertile.
Outcome measures
Outcome measures included 30-day all-cause mortality and emergency readmission into
any hospital within 30 days of discharge following PB-EUS. AEs included bleeding,
perforation, pancreatitis, and sedation-related. As it can be difficult to establish
from the HES if pancreatitis was the indication or a complication of PB-EUS, if it
was coded within the same admission episode, we decided to exclude the subjects from
the analysis of AEs if they had ICD-10 codes for acute pancreatitis concurrent with
their PB-EUS and include the subjects as having pancreatitis only when they were readmitted
with acute pancreatitis within 48 hours of PB-EUS. This methodology has a limitation
that pancreatitis following an inpatient PB-EUS would not be captured. For all other
complications, all complications within 7 days of post PB-EUS were included. Patients
who had ERCP 7 days before or after EUS were excluded from analysis of these AEs to
avoid difficulties with attributing the complication. Rates of surgical resection
in pancreatic cancer patients, chemotherapy, and no active cancer treatment were also
examined.
Statistical analysis
All statistical analyses were carried out using STATA SE v15. Categorical variables
are presented as numbers and percentages (%), while continuous variables are described
as median (interquartile range). Multivariable logistic regression analysis of the
factors associated with 30-day PB-EUS mortality was modeled adjusting for age, sex,
deprivation quintile, ethnicity, modified Charlson score, EUS sampling with FNA/FNB,
post-EUS diagnosis of pancreatic cancer, and provider volume of PB-EUS. Further logistic
regression analysis was performed to identify factors associated with surgical resection,
chemotherapy and no active therapy in the PB-EUS pancreatic cancer group. P < 0.05 was considered statistically significant.
Ethics
HES data are available under a data sharing agreement with NHS Digital for the purposes
of service evaluation and as such ethics approval is not required. Numbers less than
6 were censored from publication to protect subject anonymity. The study was registered
at the University Hospitals Birmingham NHS Foundation Trust.
Results
Data validation
Sandwell and West Birmingham NHS Trust performed 344 PB-EUS with a coding accuracy
rate of 90.8 %. Newcastle upon Tyne Hospitals NHS Foundation Trust performed 6,444
PB-EUS with a coding accuracy rate of 92.9 %. University Hospitals Birmingham NHS
Foundation Trust performed 6,672 PB-EUS with a coding accuracy rate of 97.4 %.
Cohort characteristics
During the study period (2007 to 2016), 79,269 PB-EUS procedures were performed in
68,908 subjects in England and 87 % were index procedures (Appendix 2). The median age of subjects who underwent PB-EUS was 63 (IQR 51–72) years and 56 %
were women. The majority of PB-EUS (82 %) were performed in higher-volume providers
(defined as > 816 over the study period).
Pancreatic cancer was diagnosed in 13 % of patients within 6 months of index EUS. Demographic
data for all subjects who underwent PB-EUS and the PB-EUS cohort with pancreatic cancer
are presented in [Table 1].
Table 1
Baseline characteristics of subjects undergoing PB-EUS and the PB-EUS pancreatic cancer
cohort.
|
Parameters
|
|
All PB-EUS N (%)
|
PB-EUS pancreatic cancer group N (%)
|
|
Total
|
79269
|
8840
|
|
Age
|
Median
|
63
|
68
|
|
IQR
|
51–72
|
60–75
|
|
Sex
|
Male
|
35052 (44.2)
|
4657 (52.7)
|
|
Female
|
44214 (55.8)
|
4183 (47.3)
|
|
Deprivation[1]
|
1
|
18033 (22.7)
|
1458 (16.5)
|
|
2
|
15017 (18.9)
|
1646 (18.6)
|
|
3
|
15701 (19.8)
|
1917 (21.7)
|
|
4
|
15741 (19.9)
|
1998 (22.6)
|
|
5
|
14484 (18.3)
|
1818 (20.6)
|
|
Unknown
|
293 (0.4)
|
3 (0.0)
|
|
Ethnicity
|
White
|
58921 (74.3)
|
8060 (90.8)
|
|
Asian or Asian British
|
2166 (2.7)
|
222 (2.5)
|
|
Black or Black British
|
1247 (1.6)
|
140 (1.6)
|
|
Mixed
|
347 (0.4)
|
40 (0.5)
|
|
Any other ethnicity
|
1327 (1.7)
|
169 (1.9)
|
|
Unknown
|
15260 (16.8)
|
208 (2.1)
|
|
Charlson comorbidity score
|
< 1
|
60921 (76.9)
|
6758 (76.4)
|
|
1–5
|
11968 (15.1)
|
1519 (17.2)
|
|
5
|
6380 (8.0)
|
563 (6.4)
|
|
Pancreatic cancer
|
10179 (12.8)
|
8840 (100.0)
|
|
Provider volume of PB-EUS
|
10–163
|
1,355 (2.0)
|
|
|
164–816
|
10,863 (15.8)
|
|
|
> 816
|
56,690 (82.3)
|
|
PB-EUS, pancreaticobiliary endoscopic ultrasound; IQR, interquartile range.
1 Deprivation: 1 = most deprived, 5 = least deprived.
Eighty-seven percent of subjects had a single EUS within the 6 months prior to a diagnosis
of pancreatic cancer, 11 % had two, 2 % had three, and 20 subjects had four EUS procedures
prior to pancreatic cancer diagnosis.
Changing PB-EUS and FNA practice
The annual number of PB-EUS and the percentage with FNA performed consistently increased
over the 10 years studied; 2874 PB-EUS (28 % FNA) in 2007 and 12,752 PB-EUS (35 %
FNA) in 2016. EUS-FNA particularly increased in the PB-EUS pancreatic cancer group
from 43 % in 2007 to 78 % in 2016 ([Fig. 1]).
Fig. 1 Changes in the annual number of pancreaticobiliary endoscopic ultrasound-guided fine-needle
aspirations or biopsies in subjects with a subsequent pancreatic cancer diagnosis.
PB-EUS, pancreaticobiliary endoscopic ultrasound; FNA, fine-needle aspiration or biopsy;
PC, pancreatic cancer.
Post PB-EUS adverse events
The coded adverse events (AEs) following PB-EUS are shown in [Table 2]. Sedation related events and acute pancreatitis were coded in 0.5 % and 0.2 % cases
respectively. EUS-FNA was associated with a significantly higher rate of acute pancreatitis
(0.4 % vs 0.09 %).
Table 2
Post pancreaticobiliary endoscopic ultrasound adverse events.
|
All N (%)
|
EUS-FNA N (%)
|
No FNA N (%)
|
P value
|
|
Number of procedures
|
79269
|
27239
|
52030
|
|
|
Bleeding
|
36 (0.05)
|
17 (0.06)
|
19 (0.04)
|
0.10
|
|
Perforation
|
27 (0.03)
|
13 (0.04)
|
14 (0.02)
|
0.19
|
|
Pancreatitis
|
160 (0.2)
|
114 (0.42)
|
46 (0.09)
|
< 0.001
|
|
Sedation related
|
370 (0.5)
|
139 (0.5)
|
231 (0.4)
|
0.21
|
PB-EUS, pancreaticobiliary endoscopic ultrasound; EUS-FNA, endoscopic ultrasound-guided
fine-needle aspiration or biopsy.
Post PB-EUS mortality
A total of 1070 deaths (1.5 %) were reported within 30 days of index PB-EUS. Sixty-
and 90-day mortality was reported in 3.7 % and 5.5 % of subjects. In the PB-EUS pancreatic
cancer group, 2.8 % of subjects died within 30 days of their EUS, 9 % within 60 days
and 15 % within 90 days ([Table 3]).
Table 3
Mortality following pancreaticobiliary endoscopic ultrasound.
|
All PB-EUS patients
|
PB-EUS pancreatic cancer cohort
|
|
All
N (%)
|
EUS-FNA
N (%)
|
Multiple EUS between index and death
N (%)
|
All subjects
N (%)
|
EUS-FNA
N (%)
|
Multiple EUS between index and death
N(%)
|
|
Total number of subjects
|
68908
|
24719
|
1599
|
8840
|
6595
|
521
|
|
30-day mortality
|
1070 (1.5)
|
634 (2.6)
|
46 (2.9)
|
251 (2.8)
|
182 (2.8)
|
16 (3.1)
|
|
60-day mortality
|
2525 (3.7)
|
1633 (6.6)
|
99 (6.2)
|
792 (9)
|
584 (8.9)
|
37 (7.1)
|
|
90-day mortality
|
3821 (5.5)
|
2490 (10)
|
155 (9.7)
|
1329 (15)
|
996 (15.1)
|
66 (12.7)
|
PB-EUS, pancreaticobiliary endoscopic ultrasound; EUS-FNA, endoscopic ultrasound-guided
fine-needle aspiration or biopsy.
On multivariable analysis, increasing age, male sex, increasing comorbidities, and
pancreatic cancer predicted higher mortality. Among procedural factors, FNA and lower-volume
EUS providers were associated with higher mortality ([Table 4]).
Table 4
Multivariable analysis of factors associated with 30-day post pancreaticobiliary endoscopic
ultrasound mortality.
|
Parameters
|
Odds Ratio
|
95 % CI
|
P value
|
|
Age
|
1.03
|
1.03–1.04
|
< 0.001
|
|
Sex
|
Female
|
Reference
|
|
Male
|
1.38
|
1.24–1.56
|
< 0.001
|
|
Deprivation[1]
|
1
|
Reference
|
|
2
|
0.93
|
0.78–1.13
|
0.471
|
|
3
|
0.87
|
0.72–1.04
|
0.130
|
|
4
|
0.82
|
0.68–0.99
|
0.038
|
|
5
|
0.76
|
0.62–0.93
|
0.007
|
|
Unknown
|
0.34
|
0.05–2.44
|
0.281
|
|
Ethnic group
|
White
|
Reference
|
|
Asian or Asian British
|
1.20
|
0.85–1.70
|
0.307
|
|
Black or Black British
|
0.67
|
0.38–1.20
|
0.178
|
|
Mixed
|
0.62
|
0.15–2.53
|
0.509
|
|
Any Other Ethnicity
|
0.94
|
0.58–1.54
|
0.817
|
|
Unknown
|
1.08
|
0.91–1.29
|
0.352
|
|
Charlson comorbidity score
|
< 1
|
Reference
|
|
1–5
|
1.49
|
1.27–1.74
|
< 0.001
|
|
> 5
|
2.99
|
2.56–3.50
|
< 0.001
|
|
EUS-FNA
|
2.26
|
1.98–2.57
|
< 0.001
|
|
Pancreatic cancer
|
1.39
|
1.19–1.62
|
< 0.001
|
|
Provider volume of PB- EUS
|
> 816
|
Reference
|
|
164–816
|
1.20
|
1.02–1.41
|
0.025
|
|
10–163
|
2.83
|
2.15–3.73
|
< 0.001
|
PB-EUS, pancreaticobiliary endoscopic ultrasound; EUS-FNA, endoscopic ultrasound-guided
fine-needle aspiration or biopsy; CI, confidence interval.
1 Deprivation: 1 = most deprived, 5 = least deprived.
Factors associated with surgical resection, chemotherapy, and no active treatment
in the PB-EUS pancreatic cancer cohort
Twenty-four percent of patients in the PB-EUS pancreatic cancer cohort had a surgical
resection: 12.4 % had surgery alone; 0.7 % received neoadjuvant chemotherapy; 10.3 %
had adjuvant chemotherapy; and 0.5 % received both neoadjuvant and adjuvant chemotherapy.
Forty-three percent of patients received chemotherapy alone and 33 % of subjects did
not receive any oncological or surgical treatment. Multivariable analysis of the variables
associated with the likelihood of undergoing a surgical resection, chemotherapy alone,
or no active treatment are presented in [Table 5].
Table 5
Multivariable analysis of factors associated with the likelihood of surgical resection,
chemotherapy alone and no active therapy in the pancreaticobiliary endoscopic ultrasound
pancreatic cancer cohort.
|
Variables
|
Surgical resection
N = 2111 (24 %)
|
Chemotherapy alone
N = 3809 (43 %)
|
No active therapy
N = 2920 (33 %)
|
|
0 R (95 %CI)
|
P value
|
0 R (95 %CI)
|
P value
|
0 R (95 %CI)
|
P value
|
|
Age
|
0.97 (0.96–0.97)
|
< 0.001
|
0.99 (0.99–1.00)
|
< 0.001
|
1.04 (1.04–1.05)
|
< 0.001
|
|
Gender
|
Male
|
Reference
|
|
Female
|
1.07 (0.97–1.19)
|
0.164
|
0.95 (0.88–1.04)
|
0.27
|
0.99 (0.90–1.09)
|
0.85
|
|
Deprivation[1]
|
1
|
Reference
|
|
2
|
1.09 (0.92–1.29)
|
0.340
|
1.20 (1.04–1.39)
|
0.012
|
0.76 (0.65–0.88)
|
< 0.001
|
|
3
|
1.12 (0.95–1.33)
|
0.177
|
1.26 (1.10–1.45)
|
0.001
|
0.70 (0.60–0.81)
|
< 0.001
|
|
4
|
1.31 (1.11–1.55)
|
0.001
|
1.20 (1.04–1.38)
|
0.012
|
0.65 (0.56–0.75)
|
< 0.001
|
|
5
|
1.33 (1.12–1.57)
|
0.001
|
1.14 (0.99–1.31)
|
0.076
|
0.68 (0.58–0.79)
|
< 0.001
|
|
Ethnic group
|
White
|
Reference
|
|
Asian or Asian British
|
1.01 (0.74–1.38)
|
0.955
|
0.92 (0.70–1.21)
|
0.550
|
1.07 (0.80–1.45)
|
0.642
|
|
Black or Black British
|
0.72 (0.46–1.11)
|
0.136
|
0.98 (0.70–1.38)
|
0.920
|
1.29 (0.90–1.85)
|
0.167
|
|
Mixed
|
0.76 (0.36–1.60)
|
0.471
|
1.04 (0.55–1.95)
|
0.901
|
1.12 (0.55–2.28)
|
0.747
|
|
Any Other Ethnicity
|
1.07 (0.74–1.55)
|
0.709
|
1.07 (0.79–1.46)
|
0.673
|
0.87 (0.62–1.23)
|
0.436
|
|
Unknown
|
0.48 (0.32–0.72)
|
< 0.001
|
0.96 (0.72–1.27)
|
0.765
|
1.72 (1.29–2.28)
|
< 0.001
|
|
Charlson comorbidity score
|
< 1
|
Reference
|
|
1–5
|
0.96 (0.84–1.10)
|
0.530
|
0.89 (0.79–0.99)
|
0.037
|
1.19 (1.06–1.35)
|
0.004
|
|
> 5
|
0.71 (0.57–0.90)
|
0.004
|
0.65 (0.54–0.78)
|
< 0.001
|
1.93 (1.61–2.30)
|
< 0.001
|
|
Stent before EUS
|
Metal
|
1.28 (0.90– 1.81)
|
0.169
|
0.99 (0.73–1.35)
|
0.969
|
0.82 (0.58–1.15)
|
0.241
|
|
Plastic
|
1.14 (0.98–1.32)
|
0.096
|
0.94 (0.83–1.08)
|
0.394
|
0.97 (0.84–1.12)
|
0.654
|
|
Multiple EUS pre-diagnosis
|
0.80 (0.66–0.96)
|
0.017
|
1.14 (0.98–1.33)
|
0.087
|
1.03 (0.88–1.22)
|
0.697
|
|
Provider volume of PB- EUS
|
> 816
|
Reference
|
|
164–816
|
0.65 (0.56–0.75)
|
0.000
|
1.24 (1.11–1.39)
|
< 0.001
|
1.08 (0.96–1.22)
|
0.185
|
|
10–163
|
0.44 (0.26–0.74)
|
0.002
|
1.07 (0.76–1.51)
|
0.699
|
1.56 (1.10–2.22)
|
0.013
|
PB-EUS, pancreaticobiliary endoscopic ultrasound.
1 Deprivation: 1 = most deprived, 5 = least deprived.
Patients from less deprived areas were more likely to undergo surgical resection and
chemotherapy while increasing age, increasing comorbidities (Charlson comorbidity
score > 5), and lower-volume PB-EUS providers were associated with lower rates of
surgical resection and higher rates of no active treatment.
Discussion
The widespread adoption of EUS and EUS-guided tissue sampling has been a major advance
in pancreatology over the last 20 years. This is the largest population-based study
of patients who underwent PB-EUS. There was a more than four-fold increase in the
annual number of PB-EUS procedures performed during the study period. This is consistent
with the previously published findings from the United States [15] and Canada [16] and reflects the increase in availability of EUS and its emerging role in pancreaticobiliary
diseases. The proportion of subjects who were diagnosed with pancreatic cancer within
6 months of EUS remained fairly constant at 13 %. This is consistent with the fact
that the incidence rates of pancreatic cancer in the UK have not changed over the
past 10 years (European age standardized incidence rate per 100,000 population; 15.5
in 2007 vs 16.9 in 2016) [17].
EUS-guided tissue sampling has become the method of choice to investigate pancreatic
mass lesions due to its high accuracy, with a sensitivity of 85 % to 89 % and specificity
of 96 % to 99 % according to three meta-analyses [4]
[18]
[19]. Consequently, there was a substantial increase in the use of EUS-guided sampling
in the pancreatic cancer group over the course of the study period from 43 % in 2007
to 78 % in 2016.
PB-EUS is considered a safe procedure with an overall AE rate estimated to be approximately
1 % [20]. The main AEs include perforation, bleeding, pancreatitis, and those related to
sedation. The longer rigid terminal end (4–5 cm) of the echoendoscope and semi-blind
intubation and maneuvering may potentially increase the rate of perforation, compared
with upper gastrointestinal endoscopy. In the present study, perforation was reported
in 0.03 % cases, which is comparable to the previously reported range of between 0.03 %
and 0.06 % [21]
[22]. Bleeding was reported in 0.05 % cases, which is in line with reported incidence
rates of 0 % to 0.5 % in large prospective series [23]
[24]
[25]
[26]
[27]. FNA sampling was not found to be associated with an increased risk of bleeding.
Data on the severity or site of bleeding were unfortunately not available to investigate
this further. Confounding due to bleeding related to the underlying pathology being
investigated by PB-EUS remains possible. Acute pancreatitis was reported in 0.2 %
cases and its incidence was significantly higher following FNA. Similar rates of pancreatitis
were reported in a multicenter survey but it was noted that the frequency of post-EUS
pancreatitis may be underestimated by retrospective analyses [28]. In a prospective study of 100 consecutive patients, Gress et al. reported clinical
and biochemical incidence of pancreatitis in two patients (2 %), who both responded
to conservative management [29]. The association of bleeding and pancreatitis with EUS without FNA is unexpected
and it is important to recognize that this may relate to residual confounding due
to AEs related to other concurrent procedures such as percutaneous transhepatic cholangiography,
which were not excluded, or the underlying pathology being investigated by PB-EUS. The
results of the present study indicate that PB-EUS is a safe procedure with overall
a less than 1 % risk of AEs.
Data on the factors associated with early post PB-EUS mortality are scarce. In a systematic
review of more than 10,000 patients who underwent EUS-FNA, 0.02 % mortality rate was
reported to be attributable to procedure-related complications [8]. In another systematic review and meta-analysis of morbidity and mortality of EUS-FNA
for cystic lesions, Zhu et al. reported a mortality rate of 0.19 % (95 % CI 0.09–0.32 %)
[9]. However, non-procedural factors e.g comorbidities and variation between different
providers were not studied, which are potentially important confounders of post-EUS
outcomes. In the present study, 30-day post-PB-EUS all-cause mortality was recorded
in 1.5 % of all patients and 2.8 % of PB-EUS patients with pancreatic cancer. On multivariable
analysis, increasing age, male sex, and increasing comorbidity were associated with
30-day mortality. Among procedure-related factors, lower-volume providers and EUS-FNA
were associated with higher mortality. Although EUS-FNA is reported to be safe with
a low risk of morbidity and mortality [9], it may be a surrogate for significant pancreaticobiliary pathology, which may explain
the association with mortality. Causes of deaths were not analyzed and it is possible
that fatal complications of other invasive procedures such as surgery within 30 days
of PB-EUS might have contributed in a small number of cases.
Pancreatic cancer is the fifth most common cause of cancer deaths in UK with a 1-year
survival rate of only 25 % [30]. Thirteen percent of patients were diagnosed with pancreatic cancer within 6 months
of the index EUS. While suspected pancreatic cancer is an important indication for
PB-EUS, the majority of patients undergo the procedure for a benign indication, such
as investigation of pancreatic cysts, unexplained pancreatitis, biliary type pain,
unexplained dilated common bile duct, and for therapeutic intervention. It is not
possible to determine the indication for each EUS from HES; however, a study published
from an English cancer center in the early part of this study period reported on an
annual case load approaching 700 EUS per year, of which, 5 % were for drainage procedures,
29 % EUS-FNA for suspected malignancy and cysts, and 66 % for a benign indication
[31]. Surgical resection is the only curative therapy but most of the patients are diagnosed
at an advanced stage, which precludes curative treatment. Twenty-four percent of patients
with pancreatic cancer studied had a surgical resection, which is higher than the
10 % of patients undergoing surgical resection for pancreatic cancer in the UK [32]. This difference likely reflects selection bias. In a population-based study of
pancreatic cancer patients, utilizing the SEER database, Ngamruengphong et al. also
reported that patients who underwent EUS were more frequently offered curative treatment
than those who did not and they were diagnosed at an earlier stage [11].
Patients who underwent PB-EUS through lower-volume providers were less likely to receive
surgical treatment. This difference may at least in part be due to patients considered
more likely to be suitable for surgery being transferred to higher-volume centers
for multidisciplinary management including EUS. The presence of metallic or plastic
stents prior to PB-EUS did not impact the likelihood of surgical treatment. It was
noted that 33 % of patients with pancreatic cancer did not receive any specific treatment,
probably due to advanced disease at the time of diagnosis. The need for a definitive
tissue diagnosis to exclude other treatable disease such as lymphoma or autoimmune
diseases may account for some of these cases. No active treatment was associated with
lower-volume PB-EUS providers as was a higher 30-day mortality rate, possibly indicating
better case selection with higher-volume providers. In England regional specialized
pancreatic cancer centers (where all surgical resections are performed) are generally
the higher-volume EUS providers. The differences associated with provider volume may
relate to multidisciplinary team discussion and planning reducing the use of EUS in
patients unlikely to benefit. The link between deprivation and reduced surgical resection
identified in this study is consistent with previous findings for all cancers [33] and pancreatic cancer specifically [34].
Although large observational studies are powerful tools for identifying risks and
associations within populations, there are a number of limitations to the present
study. There is a potential for recording bias as the accuracy of coded data depends
on the quality of the medical records and on the staff coding the records. However,
in the 2012/2013 annual report on the quality of HES records, 99.3 % of primary diagnoses
and 99.9 % of primary procedure codes were accurate [35]. Validation of EUS codes in our study revealed that coding accuracy was above 90 %.
Unfortunately, important data such as smoking, body mass index, performance status,
and pancreatic cancer staging details were unavailable in the HES dataset. Important
procedure-related details such as the procedural experience of the endoscopist and
whether any technical difficulties were encountered are also not recorded in HES. Detailed
data on the causes of deaths were not available, hence it was not possible to definitively
explain the relatively high 90-day mortality in all patients undergoing PB-EUS (5.5 %).
However, in addition to pancreatic cancer, underlying comorbidities and non-pancreatic
cancer pancreaticobiliary pathology e.g cholangiocarcinoma, large pancreatic pseudocysts,
and necrotizing pancreatitis are all associated with higher mortality and likely to
have contributed to the mortality figures. Finally, the link between a pancreatic
cancer diagnosis and PB-EUS is through coding records rather than directly from cancer
registry data. It is not possible to ascertain in HES if a pancreatic cancer diagnosis
was based on the histology obtained from EUS and this study relied instead on the
temporal association between pancreatic cancer diagnosis and PB-EUS procedural coding.
Conclusions
PB-EUS activity significantly increased in England from 2007 to 2016 with an increasing
proportion of FNA in patients with pancreatic cancer. A significant proportion of
patients who underwent EUS and had a diagnosis of pancreatic cancer did not undergo
surgery or receive chemotherapy. Deprivation and lower provider PB-EUS volume were
associated with increased 30-day mortality rates and reduced rates of surgical resection
for pancreatic cancer. EUS and tissue sampling should not be performed unless they
will clearly influence decision regarding surgery or chemotherapy.