Keywords endoscopy - gastric cancer - screening
Introduction
Gastric cancer is one of the most common cancers in the world with 70% incidence in
developing countries in East Asia, South America, and Eastern Europe.[1 ] In 2018, there were approximately 1 million new worldwide diagnoses and 780,000
deaths.[2 ] Japan, South Korea, and China are amongst the countries most affected, and mortality
varies significantly between these countries. In most parts of the world, 5-year survival
is around 20%.[3 ] In China, 5-year survival has ranged from 30 to 57%, compared to 63 to 77% in Japan.[4 ] This greater survival has been attributed to increased diagnosis of early disease,
which offers better prognosis but is challenging, given its asymptomatic or nonspecific
presentation.[4 ]
[5 ] Retrospective comparisons have shown 15.4% of gastric cancers being diagnosed at
an early stage in China compared to 68.6% in Japan.[6 ] Many tumors diagnosed in Chinese patients were larger and demonstrated more nodal
involvement.[6 ] Differences in the diagnosis of early-stage disease can at least be partially explained
by Japan and South Korea, being amongst the few countries that have implemented large
scale, population-wide screening programs for detection of early gastric cancer.[1 ]
[3 ]
Considerations in the implementation of organized screening include the costs of screening
and economic benefits anticipated from screening. Cost-effectiveness considerations
are a major reason why gastric cancer screening programs have been limited to a few
countries even though gastric cancer affects populations across the globe.[7 ] Efforts to reduce costs have included the use of ultrathin trans-nasal endoscopy,
which is used in Japan to screen for early gastric cancer and has the benefit of decreased
need for conscious sedation and increased tolerability when compared to conventional
trans-oral endoscopy.[8 ]
[9 ]
However, even with the development of trans-nasal endoscopy, many countries in Asia,
the Middle East, and Latin America that have high disease burden still do not have
widespread organized or opportunistic screening programs. One example is China, where
in 2015 there was an estimated 680,000 new diagnoses and approximately 500,000 deaths.[10 ] Some challenges that have prevented Chinese adoption of widespread organized screening
include the disparities in endoscopist training of advanced technologies such as narrow-band
imaging between rural and urban areas and the financial cost for screening this population.[11 ]
[12 ] Currently, opportunistic screening in China is not supported through social health
programs or insurance, leaving patients to shoulder the entire costs.[13 ] If the costs of screening could be reduced by using cheaper and thus more accessible
endoscopic devices in a tiered screening protocol, that would be one less barrier
for China and other countries with less-extensive healthcare resources and training
to move toward successful gastric cancer screening.
The aims of this study were to develop a low-cost gastroscope prototype using iterative
feedback from clinician endoscopists and assess the potential of the developed prototype
for gastric cancer screening and patient risk stratification by surveying clinician
endoscopists about device characteristics such as image quality and handling.
Methods
GP Development and Design Criteria
An interdisciplinary team of medical students, expert endoscopists, and engineering
researchers developed the GP. Design criteria were generated after literature review
and discussion with expert endoscopists. Focus was placed on minimizing the potential
cost of device production and clinical costs of use including the need for expensive
equipment and infrastructure as well as the costs of anesthesia, and additional clinician
staffing. Other important design criteria included maintaining adequate visual quality,
and device maneuverability necessary to visualize all relevant anatomical areas of
the stomach. Throughout the development process of the GP, feedback and data were
continuously collected from clinicians to guide the improvements needed in subsequent
prototypes.
Gastroenterology faculty and fellows from the University of Wisconsin School of Medicine
and Public Health, Department of Medicine and Division of Gastroenterology and Hepatology
were recruited to participate in surveys. Participants provided informed consent and
were given adequate time to ask questions before and after participation in this study.
The University of Wisconsin IRB approved this study.
Video Quality Assessment
For GP version 1, 21 participants viewed pre-recorded videos from an early prototype
and HD-WLE captured on an upper GI training model device and assessed video quality
subjectively via the blinded absolute category rating (ACR) method, which has been
used in previous studies[14 ] (Supplement 1). Recordings were captured from four anatomical areas. Participants
were surveyed via 5-point Likert scale questions (1= poor, 5 = excellent) on seven
different imaging quality metrics using the ACR method for subjective ratings of video
quality, which has been shown to give reliable and reproducible results for video
quality ratings.[15 ]
[16 ] In addition to the ACR assessment of video quality, participants answered the Likert
scale (1= strongly disagree, 5 = strongly agree) level of agreement to the following
statements: “The image quality/fidelity of the two systems were generally comparable,”
“I could tell the difference between standard endoscopic image and the new device.”
Supplementary Video S1 This video walks through use of the GP Version 2.1 in a training model.
For GP version 2, 13 participants navigated the GP in the same upper GI training model.
They then answered the Likert scale (1= strongly disagree, 5 = strongly agree) level
of agreement with the following statements regarding imaging quality: “The image quality
is adequate for identifying discrete and/or targeted lesions (ulcers, AVMs),” “The
picture quality is adequate for identifying subtle lesions (e.g., mucosal erosions,
mild gastritis, mild mucosal irregularities).” They were also asked to subjectively
compare image quality to standard adult gastroscopy as inferior, equivocal, or superior.
GP Feedback and Maneuverability
For the GP version 1 participants (n = 21) answered Likert scale (1 = strongly disagree, 5 = strongly agree) level of
agreement with the following statement, “This device concept and its future iterations/improvements
may be beneficial for screening upper GI pathology in resource-limited countries.”
In GP version 2, participants (n = 13) handled the device in the GI training model and answered Likert scale (1 = strongly
disagree, 5 = strongly agree) level of agreement to the following statement. “The
handling/maneuverability of the device is sufficient for visualizing anatomy in the
stomach including the retroflexion view.” During each interaction between our participants
the GP and at every stage of its development, participants also had the ability to
provide verbal and written feedback regarding concerns and suggestions.
Statistical Methods
Statistical analysis of subjectively rated video quality via ACR methodology used
paired t -tests and a linear mixed-effects modeling. A p -value < 0.05 was considered statistically significant. Statistical analysis was not
performed on subsequent image quality comparisons or on assessment of device handling
as these were based on more descriptive surveys.
Results
GP Device
Iterations in the design of the GP device are shown in [Fig. 1 ]. Components utilized, and assembly, and features of the various versions are included
in Supplement 2. Version 2.1 is shown in [Fig. 2 ]. This version featured a diameter of approximately 7 mm at its head and widest point,
leading to a cross-sectional dimension approximating 40 mm2 compared to the version 1 GP at 108 mm2 . The final design was based on the modification of a commercial borescope device
with video capabilities of 1080 p resolution at 30 fps capture with built in lighting
and digital zoom functionality. Modifications included the addition of a 63.5 mm compression
spring support with actuation wires strung inside, plus a handle to manipulate the
tension of the wires, which facilitate greater than 180 degrees of retroflexion.
Fig. 1 Iterations in the design and development of a low-cost gastroscope prototype. Panel
A: Version 1 prototype head. Panel B: Version 1 prototype handle. Panel C: Version
2 head with improved optics Panel D: Version 2 handle Panel E: Version 2.1 improved
retroflexion head. Panel F: Version 2.1 improved retroflexion handle.
Fig. 2 Version 2.1 prototype. Panels A–D highlight different aspects of the device from the handle to the head to the entire
device.
ACR Video Quality Assessment
Selected images taken from HD WLE and version 1 and 2 GPs are shown in [Fig. 3 ]. In the ACR video quality comparison to HD-WLE, paired t -test showed that a statistically significant lower video quality rating for the initial
GP across all 7-image metrics in each of the four image views (all p < 0.001). The ratings for all image metrics and views are represented in [Fig. 4 ]. The linear mixed-effects model examining the overall difference between GP and
HD-WLE systems across all metrics and all anatomic views showed that the ratings of
HD-WLE were significantly higher with a mean difference of 1.4150 (p < 0.0001). The largest effect size was seen in overall video ratings for the retroflexion
view for a mean of 1.9.
Fig. 3 Select still Images from HD-WLE, Version 1 and Version 2.1; 4 different anatomic
regions are shown. A portion of the externalized pull wire is seen on retroflexion
in the Version 1 (out of focus). Metal clips are seen as part of the upper GI training
model in the revised GP views.
Fig. 4 ACR video quality ratings for HD-WLE and GP Version 1; On 5-point Likert scale participants
rated the following video quality metrics: illumination/brightness, ability to identify
orientation, ability to identify important structures/landmarks, picture clarity/texture,
artefacts/background noise, contrast/border/sharpness, and overall satisfaction with
video quality from 1 (poor) to 5 (excellent). Data from four different anatomic locations:
body, antrum, pylorus and retroflex are shown here. Error bars are reflective of standard
deviations.
Likert Scale Video Quality Assessment
Participants showed a low level of agreement with the statement that the image fidelity
of the GP version 1 and HD-WLE were generally comparable (M = 2.05, SD = 1.02) ([Fig. 5 ]). Accordingly, there was also a high level of agreement with the statement that
they could tell a difference between the two imaging systems (M = 4.52, SD = 0.93)
([Fig. 5 ]).
Fig. 5 Likert scale ratings for GP Version 1: 5-point Likert agreement scale from 1 (strongly
disagree) to 5 (strongly agree). Error bars are reflective of standard deviations.
Video quality assessments for GP version 2 using Likert scale agreements showed a
strong level of agreement for ability to identify discrete and or targeted lesions
(ulcers, arteriovenous malformation [AVMS]) (M = 4.62, SD = 0.51) and subtle lesions
(mucosal erosions, mild gastritis, mucosal irregularities) (M = 4, SD = 0.7) ([Fig. 6 ]). Overall, most participants still felt image quality was inferior to adult gastroscopy
([Fig. 6 ]).
Fig. 6 Likert scale ratings for GP Version 2.1: 5-point Likert agreement scale from 1 (strongly
disagree) to 5 (strongly agree). Error bars are reflective of standard deviations.
Pie graph shows direct subjective video quality comparison of GPVersion 2.1 to HD
WLE endoscopy.
GP Device Feedback and Maneuverability
For the design of GP version 1, participants also collectively agreed with a statement
that this concept and future iterations may be beneficial for upper GI screening ([Fig. 5 ], M = 4.29, SD =0.72) ([Fig. 5 ]). Participants also shared high enthusiasm at the relatively good level of visual
fidelity for the cost but had concerns about their inability to visualize a full retroflexed
view of the lower esophageal sphincter and hiatus. Given the overall positive feedback
for the initial GP design, but poor retroflexion performance seen on ACR and in general
feedback, GPs version 2 and 2.1 focused on improving retroflexion capability and having
participants handle the device.
After iterative design of the GP, 13 participants who handled the GP version 2.1 showed
equivocal levels of agreement to statements regarding the handling and maneuverability
of the device as sufficient for visualizing anatomy in the stomach including the retroflexion
view (M = 2.69, SD =1.25) ([Fig. 6 ]).
Discussion
Because organized screening for gastric cancer began in the 1980s in Japan and the
1990s in South Korea, retrospective studies have shown a lower relative risk of death
in patients who received early screening, forming the basis of current guidelines.[1 ]
[17 ]
[18 ]
[19 ]
[20 ]
[21 ] As endoscopic methods have become more popular, research has focused on the continued
development of these technologies including methods to lower costs such as the use
of trans-nasal endoscopy.[8 ]
[9 ] Cost-effectiveness analysis is an important consideration for countries without
current organized screening that are considering adopting policies such as Singapore,
where modeling has identified that cost of screening endoscopy was a key determinate
in deciding cost-effectiveness.[7 ] There are many costs associated with endoscopic screening including device costs,
procedure-related costs, physician and support staff fees, adverse event costs, and
indirect costs. Not all these costs can be easily addressed. Designing a smaller endoscopic
device with greater comfort could and reduce the need for procedural sedation and
some ancillary clinical staff as seen in trans nasal endoscopy. Designing an endoscope
specifically for gastric cancer screening but with reduced capability for other clinical
tasks may also reduce overall device costs. Together, these changes may be a means
of first-line screening in a tiered approach before use of more traditional standard
diagnostic devices. We set out to develop such a device and assess its potential for
clinical screening.
GP Development and Device
As typical of medical device development, an iterative process of creating prototypes,
collecting expert user feedback, and then refining the design was utilized during
our GP development.[22 ] Our GP prototype is designed to be order of magnitudes lower in cost to manufacture
compared to HD-WLE, given the use of low-cost and mass-produced imaging sensors, and
a semi-custom design of adding maneuverability via a compression spring head and 3D
printed handle to an existing commercial endoscopic device. The mechanism used for
retroflexion, and maneuverability is anticipated to be much simpler and more cost-effective.
Features anticipated to lower cost in clinical operation include its small cross-sectional
size that approaches transnasal endoscopy to facilitate possible procedures without
anesthesia, and its integration of WIFI and bluetooth smartphone functionality to
minimize need for other video playback and recording equipment and infrastructure.
The prototype material and production costs for our GP 1.0 and 2.0 were estimated
to be roughly 100 US dollars. The exact production and final sales price of a commercial
GP device would be hard to estimate and would depend on overall production numbers.
We anticipate our final GP device will have the right feature/price value proposition
to succeed in gastric cancer screening compared to other low-cost endoscopy competitors
such as E.G II from South Korea and aScope from Denmark as examples.[23 ] Moreover, the other low-cost upper disposable endoscopes have limited view of esophagus
only for Barrett's screening or limited view of the stomach. In addition, there is
a significant cost of non-disposable parts with range estimated from $US 11,000–$15,000
compared to our device, which can be connected via a Wi-fi interface to smart tablet
or phone or standard computer monitor. Similar to these lower cost devices, we also
anticipate our final GP would be orders of magnitude lower than current conventional
upper endoscopes used in the United States that cost roughly 20,000 USD to acquire.[23 ]
In addition to lower anticipated costs, our design criteria also set out to create
a device with adequate optical and handling characteristics for the intended goal
of screening by complementing but not replacing HD-WLE. It is not surprising that
compared to HD WLE, in both ACR evaluation of the initial GP and subsequent expert
surveys, most participants felt the GP had inferior video quality. The clinical significance
of this remains unanswered; however, in surveys, most endoscopists felt that video
quality was satisfactory for identification of discrete and subtle lesions. Ultimately,
we set out to design and create a device to fulfill the unmet clinical need of gastric
cancer screening in developing countries with high prevalence and to achieve this
a device was proposed with certain cost, imaging, and handling metrics not yet available
on the market. While, further iterative design and research is needed before clinical
testing and use, we believe our initial design and results show promise.
Other Considerations for Gastric Cancer Screening and Diagnosis
Even with a clinically proven device with good video quality and maneuverability,
an endoscopist must still clinically interpret findings. Despite using conventional
gold-standard HD-WLE endoscopes, early gastric cancer lesions are known to be difficult
to grossly identified due to their size and appearance.[6 ]
[24 ] In retrospective studies of patients diagnosed with gastric cancer, roughly 11%
had an endoscopy within the last 1 to 3 years of their diagnosis, suggesting the possibility
of missed lesions.[25 ] In some centers, it has been reported that roughly 73% of missed diagnoses may be
attributed to endoscopist error in either not recognizing lesions or not taking biopsies.[26 ] The clinical challenge of visual identification of early gastric cancer may be exacerbated
in an approach that relies on lowering the cost of and expanding access to endoscopic
screening in low-resource countries that also lack access to well-trained endoscopists.
To address this challenge, we anticipate future features such as telemedicine, possible
with cell phone compatible capabilities of the GP version 2, as well as future directions
in technical development such as real-time computational algorithmic and deep learning
methods to aid in the identification lesions. For example, the GP with its WIFI and
smart device integration could be easily adapted for transmitting recordings via telehealth
to centers with more experience. Use of real-time computational methods and AI, although
less tested in clinical settings, has already been demonstrated with HD-WLE to be
more accurate, sensitive, and specific than experienced endoscopists in identifying
early gastric cancer on test videos.[27 ] How such algorithms would fare using lower cost devices such as the GP is unclear.
While some image recognition algorithms have been shown to be negatively affected
by lower quality image, this was most pronounced in situations of lower resolution.[28 ] Of note, the GP captures at 1080p HD resolution, just like HD-WLE, suggesting possible
similar effectiveness. If a future low-cost device such as the GP could leverage telemedicine
and computation methods together, this could negate the disparities and difficulties
in diagnosis of early cancer lesions as well as manage the workload burden of more
experienced endoscopists.
Limitations
Here we describe both the development and assessment of a GP. The device assessment
was non-randomized and without control group. While lack of randomization may have
biased device assessment, we felt at the current early stage of GP development, the
benefits of having all participants assess and provide feedback for the GP to aid
in the iterative design process of continual prototype development and clinician feedback
would outweigh potential cons. Future prototypes would benefit from double-blinded,
randomized, and controlled assessments. Other possible sources of bias during ACR
video quality surveys may include the possible early identification of each system
even though participants were blinded to each system as the video from HD-WLE included
a circular aspect ratio versus a square aspect ratio from GP. which may have been
noticed by participants. To mitigate bias, similar video dimensions/resolutions were
used for each system. Even with these potential flaws, overall participants felt that
HD-WLE had better video quality as expected. Other limitations include the use of
a phantom upper GI training model instead of physiologic patient or animal videos.
Future reiterations of GP device would need to undergo pre-clinical trials in animal
(e.g., porcine-swine) models and subsequently in human subject trials and comparing
with standard high-definition gastroscopes perhaps in tandem and/or randomized controlled
fashion.
Future GP Development and Use Case
In addition to the research questions not addressed by this study, further work includes
refinement of the GP device by enhancing video quality, ergonomics, and handling.
In the future other imaging features such as digital spectral imaging color enhancement
could also be implemented. Such features may provide additional benefit in identification
of pathology but may possibly add to the cost of the final device. Finally, the addition
of a modular, disposable exterior channel for both insufflation and aspiration of
liquid biopsy could have future value if gastric liquid biopsy can be extended to
have a role in screening. We anticipate a device with both reusable and nonreusable
single use components as described above. Studies will need to be conducted to determine
safe procedures for reuse and safe levels of reuse for reusable components. Eventually,
such a device may fulfill a role in a tiered endoscopic screening approach to identify
patients with concerning features and pipelining them to receive traditional EGD for
biopsy and treatment. This development could complement developments in noninvasive
tests such as serologic pepsinogen assays and Helicopylori pylori testing in ABC type algorithm or transabdominal ultrasounds with oral contrast.[1 ]
[29 ]
H. pylori testing and eradication have been touted by various international consensus committees
as a focus for cost-effective gastric cancer prevention, given its involvement in
the pathogenesis of gastric cancer.[30 ] As noninvasive or less-invasive testing develops, we anticipate that a low-cost
endoscopic system may still have value to confirm disease in the case of positive
results.
Ultimately, cost is just one major factor amongst many other key criteria such as
complication rate, and acceptance by both endoscopists and patients that will affect
widespread adoption by a country for medical use. In this proof-of-concept study,
we have just begun to address the potential of technological developments to lower
the cost of endoscopic devices for screening. Further research and development are
needed before clinical use. Any expansion of an endoscopic first screening approach
to countries with high need and less resources may necessitate the adoption of new
technologies that can leverage lower cost devices and use advancements such as telemedicine
and AI. In this study, we tried to develop such a tool in the form of a low-cost gastroscope,
and based on our clinician survey results, we believe this approach is promising.
Ideally, such tools can identify high-risk individuals and direct them to standard
of care techniques with more experienced endoscopists. This would hopefully expand
the access to screening and potentially benefit global health by lowering the overall
disease burden of gastric cancer.
