Introduction
Upper gastrointestinal cancers (UGICs) are usually diagnosed by endoscopy; however,
UGIC can be diagnosed after an endoscopy that did not identify the cancer. These are
termed post-endoscopy UGICs (PEUGICs). The British Society of Gastroenterology (BSG)
recommends that PEUGIC should be a quality standard and regularly audited [1]. In a meta-analysis, 11.3 % of UGICs were not diagnosed at an endoscopy performed
up to 3 years before the diagnosis [2], and more recent studies report PEUGIC rates of 6.7 %–9.4 % [3]
[4]
[5]
[6]. PEUGICs are less likely to present with alarm symptoms and are more commonly associated
with less advanced clinical stage [7]. Other associated factors include younger age, female sex, increasing deprivation,
and an inadequate number of biopsies [5]
[6]
[8], but not endoscopist experience [9]; however, the studies published to date have lacked a systematic analysis approach
to the causes of PEUGIC.
Colorectal cancer (CRC) diagnosed following a colonoscopy that did not diagnose the
CRC is termed post-colonoscopy CRC (PCCRC) [10]. The World Endoscopy Organization (WEO) has proposed that PCCRC should be categorized
into interval and non-interval cancers and has provided a system to determine the
most plausible etiologies [11] This was subsequently validated, with suggestions made to improve the categorization
system [12].
We have undertaken a detailed analysis of PEUGICs to establish how many were interval
and non-interval cancers, and have developed a root cause analysis system based on
the WEO PCCRC system to identify the most plausible explanations.
Methods
Patient identification and data collection
Using International Classification of Diseases 10th revision codes, adults (> 18 years)
diagnosed with esophageal (C15), gastric (C16), and duodenal (C17) cancers were identified
at two UK endoscopy providers: Sandwell and West Birmingham NHS trust (January 2010
to December 2019) and University Hospitals of North Midlands NHS Trust (January 2017
to March 2020). Patients were excluded if they did not have an endoscopy prior to
their diagnosis or were referred from other hospitals. Other exclusion criteria included:
non-UGI cancers, neuroendocrine tumours, sarcomas, and gastrointestinal stromal tumours.
PEUGICs were defined as cancers in patients who had an endoscopy that did not diagnose
their cancer 6–36 months prior to the UGIC diagnosis. Patients who had an endoscopy
within 6 months of the UGIC diagnosis were deemed UGIC controls. If PEUGIC patients
had more than one endoscopy 6–36 months prior to diagnosis, the endoscopy that did
not diagnose cancer that was closest to the date of the cancer diagnosis was classified
as the index endoscopy. For controls, the endoscopy closest to the date of the cancer
diagnosis was the index endoscopy. All patients with UGIC or dysplasia at the two
providers are reported by an expert GI pathologist and confirmed by a second pathologist.
Endoscopies were performed with the patient under conscious sedation (using midazolam)
or with xylocaine throat spray alone, depending on the patient’s preference and the
clinical judgment of the endoscopist. Data collected included: patient variables (age
at endoscopy, sex); endoscopy variables (indication, photodocumentation of J maneuver
[gastric retroflexion] and view quality in gastric body and second part of duodenum
[D2], tolerance [well or poorly tolerated based on the endoscopy report], and endoscopy
findings); endoscopist variables (total endoscopies performed over the study period);
cancer information (diagnosis date, site, staging, differentiation, tumor size, treatment
received [endoscopic resection, surgical resection, chemotherapy, or best supportive
care only] and histological diagnosis); and other management information (surveillance
or follow-up plan, reasons for deviation from plan [patient related or administrative]).
The total number of UGI endoscopies performed by each endoscopist was extracted from
the endoscopy reporting systems. Endoscopies performed on training lists were considered
to have been undertaken by the trainer in terms of endoscopy volume and PEUGIC analysis.
Interval and non-interval cancers and root cause analysis of the most plausible explanation
for PEUGIC
Interval and non-interval cancers
Interval PEUGICs were identified before the next planned surveillance endoscopy [11]. Non-interval PEUGICs were identified at (type I) or after (type II) the next planned
surveillance endoscopy, or when no further surveillance or follow-up was planned (type
III). Examples of the PEUGIC subcategories are provided in Table 1 s (see online-only Supplementary material).
Root cause analysis of the most plausible explanation for PEUGIC
PEUGICs were categorized into six types (A to F), involving a four-step process:
Step 1 Focal or cancer-associated lesion or premalignant condition detected in the same segment
as the subsequent PEUGIC?
If Yes, proceed to Step 2; if No, proceed to Step 3.
Step 2 Lesion adequately described and photographed, adequate biopsy samples taken, and the
surveillance/follow-up plan was appropriate?
If Yes, PEUGIC categorized as “A”: lesion detected, adequate assessment and decision-making,
but PEUGIC still occurred.
If No, PEUGIC categorized as “B”: lesion detected, inadequate assessment or decision-making.
Step 3 Index endoscopy adequate or, if inadequate, recognized by the endoscopist as inadequate
and planned follow-up was appropriate?
If Yes, PEUGIC categorized as “C”: possible missed lesion, endoscopy and decision-making
adequate.
If No, PEUGIC categorized as “D”: possible missed lesion, endoscopy or decision-making
inadequate.
Step 4 If the management pathway deviated from the recommendations following the index endoscopy,
the following categories were identified:
Where due to patient choice or the decision of the responsible clinician that the
patient was not fit for further investigations, “E”: deviated from management pathway
but appropriate.
Where due to administrative delays (i. e. surveillance or follow-up procedures not
booked within the recommended timeframe), “F”: deviated inappropriately from management
pathway.
More than one PEUGIC explanation was allowed for individual patients. Detected lesions
in the PEUGIC segment included premalignant (Barrett’s esophagus, gastric atrophy,
or gastric intestinal metaplasia), and focal or cancer-associated lesions (esophageal
ulcer or stricture, Los Angeles grade C or D reflux esophagitis, or gastric ulcer).
Endoscopies performed 6 weeks beyond the planned follow-up date (for focal lesions)
and 12 weeks beyond the planned surveillance dates (for premalignant conditions) were
categorized as inappropriate and related to administrative factors, in the absence
of patient choice or an intercurrent illness that delayed the endoscopy.
An endoscopy was considered adequate if the following criteria were met:
-
high definition video-endoscopy with image capture and biopsies
-
J maneuver performed and photographed
-
D2 intubated and photographed
-
view quality in the stomach photographed and classified as excellent, good, or satisfactory,
with no foam, mucus, blood, or food limiting the view
-
tolerance excellent, good, or satisfactory and not limiting the view.
Photodocumentation of the J maneuver, D2, and gastric body were the minimum criteria
for adequate photodocumentation.
Avoidability
The previously described approach used to define avoidable PCCRC [12] was used to determine whether a PEUGIC was potentially avoidable based on cancer
size at diagnosis and the factors identified on root cause analysis. Small PEUGICs
were categorized as unavoidable if they were growing by < 5 mm/year, as they would
have been unlikely to be detectable during the index endoscopy. PEUGICs were also
considered unavoidable if the recommended pathway was not followed because the patient
declined investigations or was deemed by the responsible clinician to be too frail
to proceed with further investigation. All other PEUGICs were considered potentially
avoidable.
Potential impact of delay in diagnosis on PEUGIC clinical outcomes
The outcome for a PEUGIC was unlikely to be different if patients were diagnosed at
an early stage despite a negative index endoscopy and later underwent successful endoscopic
resection. The outcome was also unlikely to be different for patients who were frail
at index endoscopy and were unlikely to be eligible for curative treatment at any
stage. Patients diagnosed with their cancer at an advanced stage that precluded curative
treatment or endoscopic resection were considered to have potentially had a different
outcome had they been diagnosed at index endoscopy.
Attribution
PEUGICs were attributable to individual endoscopists if technical endoscopic or decision-making
factors were identified on the root cause analysis [12]:
-
premalignant, focal, or cancer-associated lesion identified but not described according
to the recommended criteria (e. g. Prague classification [13]
[14]) or lesion site or morphology not recorded in the endoscopy report or photographed
-
premalignant, focal, or cancer-associated lesion identified but not biopsied appropriately
or according to recommended guidelines where relevant (e. g. Seattle protocol for
Barrett’s esophagus [13]
[15] and Sydney protocol for gastric atrophy and intestinal metaplasia [16])
-
endoscopist did not recommend an appropriate surveillance or follow-up plan
-
if the index endoscopy was inadequate, the endoscopist did not recognize it as inadequate
or did not recommend a repeat procedure.
PEUGICs were not deemed attributable in the following situations:
-
small PEUGIC (growing at < 5 mm/year)
-
the patient declined further investigations or was deemed by the responsible clinician
to be too unwell for further investigation.
For each endoscopist, the total and mean annual number of UGI endoscopies performed
over the study period were extracted. The “technically attributable” rate per 1000
endoscopies was calculated for each endoscopist by dividing the technically attributable
PEUGIC number by the total number of UGI endoscopies.
Statistical analysis
The Mann–Whitney U test and chi-squared test were used for continuous and categorical variables respectively,
and two-sided P values < 0.05 were considered significant. Spearman’s rank correlation was used to
assess correlations between the technically attributable PEUGIC rate per 1000 endoscopies
and the mean annual number of endoscopies by endoscopists.
A funnel plot examined variation in technically attributable PEUGIC rates between
endoscopists. It was constructed as a scatter plot with superimposed control limits,
representing one and two SDs from the mean. Endoscopists outside the control limits
had a significantly higher technically attributable PEUGIC rate than the mean. Scatter
plots were used to correlate the delay in diagnosis (interval from index endoscopy
to PEUGIC diagnosis) and cancer stage (I, II, III, or IV) and histological differentiation
(categorized as well, moderately, and poorly differentiated) for all PEUGICs and also
separately for PEUGICs with and without Barrett’s esophagus.
Stata statistical software, release 16, was used for the statistical analysis.
Ethics
This work was undertaken as a service improvement project and ethics approval was
not sought. It was registered with Trust Audit and Quality Improvement Departments
of Sandwell and West Birmingham NHS Trust and University Hospitals of North Midlands
NHS Trust.
Patient and public involvement
There was no patient or public involvement in this study.
Results
Study subjects
A total of 1327 UGICs met the inclusion criteria ([Fig. 1]); 89 (6.7 %) were PEUGICs. Of these, 48 % were diagnosed 6–18 months after the index
endoscopy and 52 % were diagnosed 18–36 months after the index endoscopy. The patient
demographic details and characteristics of the index endoscopy for patients with PEUGIC
and the UGIC controls are shown in [Table 1].
Fig. 1 Flowchart describing reasons for exclusion and selection of study patients.
UGI, upper gastrointestinal; SWBNHST, Sandwell and West Birmingham NHS trust; UHNM
NHST, University Hospitals of North Midlands NHS Trust.
Table 1
Patient demographic details and index endoscopy characteristics of the post-endoscopy
upper gastrointestinal cancer (PEUGIC) and upper gastrointestinal cancer (UGIC) control
groups.
|
Total
|
UGIC control
(n = 1238)
|
PEUGIC
(n = 89)
|
P value
|
|
Location, n (%)
|
< 0.001
|
|
|
750 (60.6)
|
74 (83.1)
|
|
|
467 (37.7)
|
15 (16.9)
|
|
|
1 (0.1)
|
0
|
|
|
20 (1.6)
|
0
|
|
|
Sex, male, n (%)
|
839 (67.8)
|
54 (60.7)
|
0.16
|
|
Age at endoscopy, median (IQR), years
|
73 (65–80)
|
73.5 (63.5–81)
|
0.87
|
|
Indication for endoscopy, n (%)
|
< 0.001
|
|
|
1017 (82.1)
|
40 (44.9)
|
|
|
117 (9.5)
|
22 (24.7)
|
|
|
14 (1.1)
|
24 (27.0)
|
|
|
34 (2.7)
|
2 (2.2)
|
|
|
56 (4.5)
|
1 (1.1)
|
|
Role of endoscopist, n (%)
|
0.39
|
|
|
659 (53.2)
|
46 (51.7)
|
|
|
174 (14.1)
|
12 (13.5)
|
|
|
265 (21.4)
|
16 (18.0)
|
|
|
94 (7.6)
|
12 (13.5)
|
|
|
46 (3.7)
|
3 (3.4)
|
|
Endoscopic diagnosis, n (%)
|
< 0.001
|
|
|
0 (0.0)
|
12 (13.5)
|
|
|
1057 (85.4)
|
2 (2.2)†[2]
|
|
|
19 (1.5)
|
36 (40.5)
|
|
|
24 (1.9)
|
5 (5.6)
|
|
|
9 (0.7)
|
3 (3.4)
|
|
|
11 (0.9)
|
6 (6.7)
|
|
|
68 (5.5)
|
0 (0.0)
|
|
|
48 (3.9)
|
31 (34.8)
|
1 Others comprised consultant physicians other than gastroenterologists.
2 Declined curative therapy.
Cancer details
The majority of PEUGICs were esophageal (83 %), with 17 % being gastric. Data on the
clinical staging, treatment received, and stratification based on an index endoscopy
finding of Barrett’s esophagus are presented in [Table 2]. Among the PEUGICs, 57 % were early stage (i. e. stage I or II), compared with 22 %
of the UGIC controls. No correlation was found between the interval from the index
endoscopy to PEUGIC diagnosis and tumor size, staging at diagnosis, or histological
differentiation (Fig. 1 s). More than half of PEUGIC patients received treatment with curative intent (53 %),
compared with 29 % of the UGIC controls (P = 0.002). Patients with PEUGICs were more likely to undergo endoscopic resection
than the UGIC controls (31.3 % vs. 5.1 %; P = 0.002).
Table 2
Comparison of clinical staging and treatment received by all patients, with further
stratification of the post-endoscopy upper gastrointestinal cancer (PEUGIC) patients
by index endoscopy findings of Barrett’s esophagus.
|
All cancers
|
PEUGICs
|
|
Total, n (%)
|
UGIC control, n (%)
|
PEUGIC, n (%)
|
P value
|
Barrett’s esophagus, n (%)
|
No Barrett’s esophagus, n (%)
|
P value
|
|
Total
|
1327 (100)
|
1238 (100)
|
89 (100)
|
|
36 (100)
|
53 (100)
|
|
|
Clinical stage at diagnosis
|
|
Early
|
I
|
148 (11.2)
|
112 (9.0)
|
36 (40.5)
|
< 0.001
|
29 (80.6)
|
7 (13.2)
|
< 0.001
|
|
II
|
179 (13.5)
|
164 (13.2)
|
15 (16.9)
|
3 (8.3)
|
12 (22.6)
|
|
Advanced
|
III
|
401 (30.2)
|
390 (31.5)
|
11 (12.4)
|
1 (2.8)
|
10 (18.9)
|
|
IV
|
450 (33.9)
|
429 (34.7)
|
21 (23.6)
|
3 (8.3)
|
18 (34.0)
|
|
Not available
|
149 (11.2)
|
143 (11.6)
|
6 (6.7)
|
0.260
|
0 (0.0)
|
6 (11.3)
|
0.141
|
|
Treatment
|
|
Curative
|
Endoscopic resection
|
86 (6.5)
|
60 (4.8)
|
26 (29.2)
|
< 0.001
|
20 (55.6)
|
6 (11.3)
|
< 0.001
|
|
Surgical resection
|
225 (17.0)
|
209 (16.9)
|
16 (18.0)
|
9 (25.0)
|
7 (13.2)
|
|
Chemo-radiotherapy
|
73 (5.5)
|
71 (5.7)
|
2 (2.2)
|
0 (0.0)
|
2 (3.8)
|
|
Palliative therapy[*]
|
943 (71.1)
|
898 (72.5)
|
45 (50.6)
|
7 (19.4)
|
38 (71.7)
|
UGIC, upper gastrointestinal cancer.
* 657 patients had best supportive care only.
Index endoscopy details for PEUGIC patients
In 27 % of the PEUGIC patients, the index endoscopy was for Barrett’s surveillance
compared with 1.1 % in the UGIC control group. In PEUGIC patients, views were excellent
or good in 47.2 % and satisfactory in 25.8 %; four patients (4 %) had poor views due
to gastric food residue and in 22.5 % the view quality was not recorded. Procedure
tolerance was not recorded in 30 % of patients, but the procedure was reported as
well tolerated in 64 % of the PEUGIC endoscopies.
Photodocumentation of gastric retroflexion was found in 38 % of the index endoscopies.
Duodenal intubation was reported in 89 % of the PEUGIC patients, but D2 photodocumentation
was found in only 32.6 %. No images were recorded in 34.8 % of endoscopies, with only
one recording that the endoscopy reporting system failed to capture images. The indications
for the index endoscopy and endoscopic diagnoses differed between the PEUGIC and UGIC
control groups ([Table 1]).
Correlation between the attributable PEUGIC rate and endoscopist data
Technical endoscopic factors were identified in 52 PEUGIC patients (58.4 %). It was
not possible to calculate the mean annual endoscopy volume for one endoscopist, who
was consequently excluded from further analyses. The technically attributable PEUGIC
rate was calculated for 23 endoscopists. A negative correlation was found between
the mean annual number of UGI endoscopies performed by endoscopists and the technically
attributable PEUGIC rate, with a correlation coefficient of −0.57 (P = 0.004). Three endoscopists were identified as outliers, one with a technically
attributable PEUGIC rate higher than 2SDs from the mean and two above 1SD from the
mean ([Fig. 2]). The mean annual number of UGI endoscopies performed by these three endoscopists
was 206 (SD 20.6).
Fig. 2 Funnel plot showing the correlation between the annual number of endoscopies performed
by individual endoscopists over the study period and the technically attributable
post-endoscopy upper gastrointestinal cancer (PEUGIC) rate.
Root cause analysis of the most plausible explanation for PEUGIC
PEUGICs were classified as non-interval in 98 % of patients: 48 % (n = 42) type I;
5 % (n = 4) type II; and 47 % (n = 41) type III. Only two PEUGICs were interval cancers,
both of which occurred in patients with Barrett’s esophagus.
Premalignant lesions were identified in 39 patients (43.8 %): 36 Barrett’s esophagus,
two gastric adenoma, and one gastric atrophy. Focal or cancer-associated lesions were
identified in 12 patients (13.5 %): four esophageal stricture, three abnormal esophageal
area, two esophageal ulcer, one severe esophagitis, one cardia inflammation, and one
gastroesophageal junction nodule. No lesion was found in 38 patients (42.7 %) ([Fig. 3] shows PEUGIC examples).
Fig. 3 Endoscopic images of a patient with post-endoscopy upper gastrointestinal cancer
showing: a in the lower esophagus of a patient with a history of chronic reflux, a small ulcer
at the gastroesophageal junction that was not biopsied (no follow-up endoscopy was
arranged); b after the patient had developed worsening dysphagia 31 months later, a large fungating
adenocarcinoma (Siewert type II) at the gastroesophageal junction, which was found
to be a stage 4 cancer with liver metastases, so the patient was referred for best
supportive care.
The results of root cause analysis of the PEUGIC patients are shown in [Fig. 4] and [Table 3]. More than one plausible explanation was found in seven patients (7.9 %): six had
inadequate biopsies and an inadequate surveillance plan, and one had an inadequate
surveillance plan and an administrative delay.
Fig. 4 Categorization of post-endoscopy upper gastrointestinal cancers (PEUGICs) based on
the most plausible explanation. Lesions included premalignant (e. g. Barrett’s esophagus,
gastric atrophy, gastric intestinal metaplasia, or gastric adenoma) and focal or cancer-associated
lesions (e. g. esophageal ulcer or stricture, Los Angeles grade C or D reflux esophagitis,
or gastric ulcer).
Table 3
Summary of the results of the root cause analysis of the most plausible explanation
for the 89 post-endoscopy upper gastrointestinal cancers (PEUGICs).
|
Type 1
|
Premalignant lesion noted (e. g. Barrett’s esophagus, gastric intestinal metaplasia
or atrophy) in the same segment as the PEUGIC
|
39 (43.8 %)
|
|
a
|
Biopsies adequate and, if Barrett’s esophagus found, segment was adequately measured,
and surveillance plan adequate and within correct timeframe, but PEUGIC still occurred
|
15 (16.9 %)
|
|
b
|
Biopsies inadequate and/or Barrett's segment not measured
|
17 (19.1 %)
|
|
c
|
Surveillance plan inadequate
|
11 (12.4 %)
|
|
d
|
Surveillance not undertaken or not undertaken within the correct timeframe but appropriate
owing to patient choice or co-morbidity
|
2 (2.2 %)
|
|
e
|
Surveillance not undertaken or not within the correct timeframe and inappropriate
|
3 (3.4 %)
|
|
Type 2
|
Focal or cancer-associated lesion noted in the same segment as the PEUGIC (e. g. esophageal
ulcer or stricture, grade C or D reflux esophagitis, gastric ulcer)
|
12 (13.5 %)
|
|
a
|
Site and morphology described and photographed, adequate biopsy sampling and follow-up
undertaken in the correct timeframe but PEUGIC still occurred
|
0
|
|
b
|
Site or morphology not described or not photographed or biopsy sampling inadequate
|
7 (7.9 %)
|
|
c
|
Follow-up plan inadequate
|
7 (7.9 %)
|
|
d
|
Follow-up not undertaken or not undertaken within the correct timeframe but appropriate
owing to patient choice or co-morbidity
|
3 (3.4 %)
|
|
e
|
Follow-up not undertaken or not within correct timeframe and inappropriate
|
0
|
|
Type 3
|
No premalignant lesion/focal or cancer-associated lesion noted in the same segment
as the PEUGIC
|
38 (42.7 %)
|
|
a
|
Possible missed lesion but prior endoscopy adequate
|
8 (8.9 %)
|
|
b
|
Possible missed lesion, with prior endoscopy not recognized by endoscopist as inadequate
|
28 (31.5 %)
|
|
c
|
Possible missed lesion, with prior endoscopy recognized as inadequate but follow-up
plan inadequate
|
3 (3.4 %)
|
|
d
|
Possible missed lesion, with prior endoscopy recognized as inadequate and follow-up
plan adequate, including no follow-up owing to patient choice or co-morbidity
|
0
|
More than one possible explanation was found in seven cases.
Barrett’s esophagus
Around 40 % of PEUGICs were diagnosed in patients with Barrett’s esophagus. The Prague
criteria were used in 94 % of patients and the Seattle biopsy protocol was followed
in 42 %. Planned surveillance intervals were incorrect in 25 %. Among the PEUGICs
in patients with Barrett’s esophagus, 89 % were diagnosed at an early stage (stage
I or II) and 81 % received treatment with curative intent (56 % endoscopic resection
and 25 % surgery).
Of 38 non-Barrett’s esophageal PEUGICs, 18 were squamous cell cancers and 20 were
adenocarcinomas, including 17 that involved the gastroesophageal junction. Categories
D (22/38) and B (12/38) were identified as the commonest most plausible explanations.
Avoidability
Of PEUGICs, 71 % were categorized as potentially avoidable. The unavoidable PEUGICs
included 21 small PEUGICs; there were also three related to patient’s choice not to
undergo further investigations and two where decisions were taken not to investigate
further owing to multiple co-morbidities and patient frailty.
Impact on clinical outcome
The clinical outcome could potentially have been different for 45 % of PEUGICs. This
included 23 patients with advanced stage (stage III or IV) at diagnosis, 14 patients
who underwent esophagectomy, and three patients who were too frail at the time of
cancer diagnosis but could potentially have been offered endoscopic resection if their
cancer had been detected at index endoscopy.
Discussion
This is the first study to report a detailed root cause analysis of unselected PEUGICs,
develop a system of analysis to categorize the causes of PEUGIC, and identify contributing
factors and missed opportunities to potentially avoid PEUGIC in 71 % of patients.
Inadequate assessment of premalignant or focal lesions, inadequate endoscopy quality,
and poor decision-making around surveillance or follow-up plans were identified as
the commonest explanations for PEUGIC. A negative correlation between the annual number
of endoscopies performed by individual endoscopists and the technically attributable
PEUGIC rate was noted.
The unadjusted PEUGIC rate was 6.7 %, which was within the target of < 10 % proposed
in a position statement on UK endoscopy quality standards [1]. However, both endoscopy providers are part of large conurbations and some patients
may have been diagnosed with PEUGIC at different providers and would not have been
captured in an analysis limited to local hospital records, meaning this is therefore
likely to be an underestimate. Studying national datasets can circumvent this problem,
as seen in the national UK PCCRC analysis [17], when 13 % of PCCRCs were diagnosed in a different provider from the one that performed
the index colonoscopy (personal communication from Drs. Roland Valori and Nicholas
Burr).
Around 40 % of PEUGICs occurred in patients with Barrett’s esophagus. A systematic
review has also described an esophageal cancer miss rate of 24 % in Barrett’s esophagus
[18]; however, 89 % of the PEUGICs in patients with Barrett’s esophagus were diagnosed
at an early stage and 81 % were amenable to curative endoscopic or surgical resection.
These results are supported by previous studies that have shown a positive impact
of Barrett’s surveillance on tumor staging and the survival of patients [19]
[20]. Of the Barrett’s PEUGICs, 56 % were treated by endoscopic resection and can therefore
be regarded as surveillance successes; nine underwent surgical resection when earlier
detection and endoscopic intervention might have avoided this outcome. The main reasons
for PEUGIC included inadequate numbers of biopsies and inadequate surveillance plans.
We would recommend that surveillance of Barrett’s esophagus, and gastric intestinal
metaplasia and atrophy should only be performed by endoscopists with adequate training,
on dedicated lists with adequate time, and using optimal mucosal enhancement techniques
[21]
[22]
[23]
[24]
[25].
Mucosal views were excellent or good in 47 % of index endoscopies; however, there
was no recommendation to repeat the endoscopy in the endoscopy reports where mucosal
views were inadequate. We suggest endoscopies should be repeated if adequate views
cannot be attained at index endoscopy despite mucosal cleansing with mucolytics and
antifoaming agents [26]
[27].
Photographs of D2 were recorded in 33 % of index endoscopies among the PEUGIC patients
and of retroflexion in 38 %. National and international guidelines recommend photodocumentation
of anatomical landmarks [1]
[28]
[29]
[30] and the widespread availability of electronic image capture means there should be
no excuse for not obtaining adequate endoscopic images. Photodocumentation of cecal
intubation and rectal retroflexion are established for colonoscopy to ensure examination
completeness and the examination of high risk areas [31]. Similar efforts are needed for UGI endoscopy to ensure that high risk areas are
adequately examined. Finally, an accurate description according to the established
classification systems [32] is of critical importance to the ongoing management and follow-up of lesions, including
correlation with histology.
We found a negative correlation between endoscopists’ annual endoscopy number and
the technically attributable PEUGIC rate. The BSG recommends that endoscopists should
perform a minimum of 100 procedures each year to maintain proficiency [1]; however, in the current study, all of the endoscopists who had performed a PEUGIC
endoscopy where an endoscopy-related contributing factor was identified had performed
more than 100 annual endoscopies. This suggests that the annual endoscopy volume currently
recommended may not be adequate, but it is important to emphasize that this assessment
was based on the analysis of only a small number of endoscopists. These findings also
highlight that further quality indicators are needed for endoscopy.
Although Barrett’s esophagus was identified as the predominant premalignant condition
in the current study, other premalignant conditions (e. g. gastric atrophy and intestinal
metaplasia) may be more common in other regions. The root cause analysis system developed
is however generalizable and will provide a framework to investigate PEUGIC in other
settings.
The present study has a number of limitations. It was a retrospective study and although
the most plausible explanations were identified, causality cannot be established.
Clinical staging was not available for 11 % of patients owing to the patient’s choice
not to have further investigations or because they had moved out of the catchment
area.
Advanced imaging techniques and longer inspection times improve the diagnostic yield
of endoscopy [22]
[25]
[33]
[34]
[35]; however, the recording of these parameters was not mandatory in the endoscopy reporting
systems at the study providers. Owing to uncertainty around whether these techniques
were used, they were not included in the proposed criteria for an adequate endoscopy
examination. We would suggest that these important measures should be included in
future PEUGIC studies. The impact of patient tolerance and sedation could not be assessed,
but this clearly merits further study as a contributing factor to PEUGIC.
It is possible that some of the endoscopists had performed endoscopies outside of
their national health service (NHS) provider and it was not possible to capture data
on these endoscopies. This could potentially bias the results of the correlation between
annual endoscopy number and technically attributable PEUGIC rate.
Evaluation of only the index endoscopy, as recommended by the WEO for PCCRC, has the
potential limitation of missing important information on a small number of patients
in whom a premalignant, focal, or cancer-associated lesion in the same segment as
the PEUGIC was detected at a prior endoscopy (before the index endoscopy), with the
lesion not being seen or recognized at the index endoscopy. Future studies should
consider examining all endoscopies prior to a cancer diagnosis, to identify if there
is any additional benefit to reviewing all endoscopies within the 3 years prior to
diagnosis. Finally, this study included two NHS providers in the UK, and the study
findings and root cause analysis system should be validated in future studies in other
parts of the world.
In conclusion, in a retrospective analysis of PEUGIC, the most common plausible explanations
were inadequate assessment or decision-making concerning premalignant, focal, or cancer-associated
lesions, and possible missed lesions in the context of an inadequate endoscopy or
decision-making following endoscopy. A systematic approach using the root cause analysis
framework developed can differentiate the technical endoscopic, decision-making, and
administrative factors that can lead to missing UGICs at both endoscopist and institutional
level, and guide quality improvement efforts to reduce the PEUGIC rate.
