Pseudobezoars: Technology Progress and New Prospects as a Medical Platform

doi:10.4236/eng.2013.55B003

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Engineering, 2013, 5, 10-14

doi:10.4236/eng.2013.55B003 Published Online May 2013 (http://www.scirp.org/journal/eng)

Pseudobezoars: Technology Progress and

New Prospects as a Medical Platform

Orly Yadid-Pecht1, Martin P. Mintchev1,2

1Department of Electrical and Computer Engineering, University of Calgary, Calgary, Canada

2Department of Surgery, University of Alberta, Edmonton, Canada

Email: [email protected], [email protected]

Received 2013

ABSTRACT

In recent years, pseudobezoars have been a subject of research, mainly serving as a basis for a new non-invasive alter-

native to obesity treatment. A pill incorporating the technology has been proven to be successful as a weight loss ther-

apy. It enables patients to sustain a diet longer, due to an increase in the level of satiety, resulting in a smaller amount of

food intake. Utilization of the tech nology has recently found new prospects in another organ of the GI tract, the colon.

Pseudobezoar technology can be utilized as an enhanced method for colon cancer screening and also as an alternative

carrier for bacterial therapy.

Keywords: Pseudobezoars; Obesity; Colon Cancer Screening; Diagnostic Device; Therapeutic Device

1. Introduction

The pseudobezoar technology is relatively new and only

recently has been granted a US patent [1]. However,

early successes of utilizing the device as a dietary pill

have already been reported [2-4]. The technology com-

prises a pill coated and targeted for the stomach, where

the shell dissolves and the superabsorbent polymer gran-

ules within expanding due to the contact with and ab-

sorption of gastric liquid. The granules are kept in the

stomach without an option to exit, since they are con-

tained in a gauze that disintegrates only after a few days.

Taking the pill in a prescribed regimen, demonstrated a

significant weight loss in a double blind study [3]. These

results confirmed the efficacy of the technology as a die-

tary pill targeted at the stomach.

We have recently described an additional possibility

for usage of the technology, targeting the colon as the

organ of choice. The method comprises use of the pseu-

dobezoar as a colon cancer screening device when taken

as a colon-targeted pill.

Section 2 will describe the current colon cancer

screening options. Section 3 will describe the utilization

of pseudobezoars as an alternative to current colon can-

cer screening technologies. Section 4 will briefly outline

the prospects of the utilizatio n of the device as a bacterial

transplant and summarize this p ape r.

2. Current Colon Cancer Screening Options

Colon cancer is the most common gastrointestinal (GI)

malignancy and the second leading cause of cancer deaths

in the United States [5]. Of the many pre-neoplastic and

neoplastic condition s in humans, nowh ere is the ability to

prevent disease as profound as it is in colon cancer [6].

Strategies for prevention have evolved over the past 15

years, now including the use of fecal occult blood test

(FOBT), fecal immunology tests (FIT), fecal DNA tests,

colonoscopy, video capsule endoscopy (VCE), and

computed tomographic (CT) colonography, also known

as Virtual Colonoscopy [7].

2.1. Fecal Occult Blood Tests

Although improved fecal occult blood tests have been

utilized, the overall sensitivity of this approach is not

impressive. In a 2005 study [8] Morikawa et al con-

cluded that the sensitivity of 1-time immunochemical

FOBT for detecting advanced neoplasia and invasive

cancer was 27.1% and 65.8%, respectively. In addition,

the sensitivity for invasive cancer detection according to

Dukes’ stages showed 50.0% for Dukes’ stage A, 70.0%

for Dukes’ stage B, and 78.3% for Dukes’ stages C or D

[9]. The sensitivity for detecting advanced neoplasia in

the proximal colon was significantly lower than that de-

tected in the distal colon (1 6. 3% vs 3 0.7%, p < 0.00007).

2.2. Fecal Immunology Tests

This testing method can be considered a refinement, ex-

tension and an additive improvement over the traditional

fecal occult blood testing. It has been reported that when

O. YADID-PECHT, M. P. MINTCHEV 11

a routine fecal occult blood test (e.g. a sensitive guaiac

test) is combined with an immunological test for human

haemoglobin, the sensitivity improves to 97% (only 3%

false negative results) in patients and no false positiv es in

controls [10]. Another far more comprehensive study [11]

found that the sensitivity of the combined test was the

highest among all occult blood tests (in the range of

80%), and its specificity for detecting cancer was above

97%. The problem of all fecal occult blood tests, how-

ever, is that they aim at discovering blood in the feces

resulting from existing bleeding colorectal lesions, while

adenomatous polyps in asymptomatic average-risk adults

remain undetected. Therefore, by the time findings are

obtained with the fecal tests, it is usually too late [12,13].

Nevertheless, the use of either annual or biennial fecal

occult-blood testing significantly reduces the risk of co-

lorectal cancer [14].

2.3. Fecal DNA Tests

Oncogene mutations that characterize colorectal neopla-

sia are detectable in exfoliated ep ithelial cells in the stoo l.

Whereas neoplastic bleeding is intermittent making the

detection of occult fecal blood more or less random,

epithelial shedding is continual, potentially making fecal

DNA testing more sensitive. Early 21st century reports

indicated that a fecal DNA test had a sensitivity of 91

percent for the detection of colorectal cancer and 82 per-

cent for the identification of adenomas[15]. However,

one other report indicated that fecal DNA testing did not

improve dramatically the preventive early detection of

colon cancer compared to occult fecal blood testing [16].

2.4. Colonoscopy

Traditional colonoscopy has been considered the gold

standard for assessing colonic abnormalities, offering

sensitivity and specificity in detecting polyps exceeding

90%. Moreover, it also offers the ability to remove polyps

during the procedure. Although classical colonoscopy

can be considered safe, reliable, real-time and quick, re-

cent population-based studies have demonstrated that the

rate of protection against colorectal cancer that it offers

was only 30% to 50% [17]. In addition, colonoscopy is

an invasive procedure, performed in a hospital setting,

requires extensive and expensive logistic preparations,

carries substantial risks of harming patien ts (2 -4/100 0), is

heavily operator-dependent, and requires post-procedural

recovery [18,19].

2.5. Video Capsule Endoscopy

Orally administered video capsule endoscope(VCE) is a

simple, safe, non-invasive, and non-sedation requiring

procedure. VCE is well accepted and tolerated by the

patients and allows complete exploration of the small

bowel. Usually, it takes 24 to 48 hours for a VCE to pass

through the entire GI tract as a result of its passive

movement from mouth to anus [20]. In view of the fact

that the movement of these capsules is controlled by

spontaneous gut peristalsis, the application of VCE is

currently limited to small-lumen organs [21]. In larger-

lumen organs, such as the stomach or the colon, the cap-

sules tend to tumble, which leads to incorrect recognition

of a given organ segment by the capsule imaging system,

thus rendering the images unsuitable for diagnostic pur-

poses and a miss rate in the colon exceeding 30% [22].

In addition, rapid colonic motility could result in in-

complete imaging considering that most of the commer-

cial CEs are designed to acquire images at a pre-fixed

frame rate, usually 2 frames per second (FPS) [23].

Moreover, tumbling movement by peristalsis also limits

the visual field and causes failure to catch significant

lesions or grossly distorts the perceived dimensions of

polyps [24].

The Pill Cam Colon capsule (Given Imaging, Yo-

qneam, Israel) is the only VCE currently in use for colo-

nic investigation. In the most recent study of 56 patients,

colon capsule endoscopy (CCE) was followed by con-

ventional colonoscopy (CSPY). Polyp detection rate (per

patient) was 50% (n = 28) for CSPY and 62% (n = 35)

for CCE. For relevant polyps (> 5 mm) there was a cor-

respondence in the detection rates of both methods (p <

0.05). The mean sensitivity was 50% (p < 0.05), the

mean specificity was 76% (p < 0.05), the positive predic-

tive value (PPV) was 20% and the negative predictive

value (NPV) was 93% [25]. These results indicate the

general problem of VCE tumblin g during its tran sit in th e

colon and the need for VCE stabilization [24]. A recent

report on self-stabilizing capsule endoscopy systems

seems to overcome this issue [26].

2.6. Computed Tomographic Colonography

(Virtual Colonoscopy)

It has been suggested th at virtual colonoscopy perfor med

with a computed tomography is an accurate screening

method for the detection of colorectal neoplasia in as-

ymptomatic average-risk adults and compares favorably

with optical colonoscopy in terms of the detection of

clinically relevant lesions. In a 2003 study [27] Pickhardt

et al. suggested that the sensitivity of virtual colonoscopy

for adenomatous polyps was 93.8 percent for polyps at

least 10 mm in diameter, 93.9 percent for polyps at least

8 mm in diameter, and 88.7 percent for polyps at least 6

mm in diameter. The sensitivity of optical colonoscopy

for adenomatous polyps was 87.5 percent, 91.5 percent,

and 92.3 percent for the three sizes of polyps, respec-

tively. The specificity of virtual colonoscopy for adeno-

matous polyps was 96.0 percent for polyps at least 10

mm in diameter, 92.2 percen t for polyps at least 8 mm in

O. YADID-PECHT, M. P. MINTCHEV

diameter, and 79.6 percent for polyps at least 6 mm in

diameter.

3. Utilization of the Pseudobezoar as a

Diagnostic Screening Device

Recently proposed pseudobezoartechnology has been

suggested for the treatment of obesity and for controlled

drug delivery in the body (see e.g. [1]). Here we suggest

to utilize these retaining devices as platforms for colon

biopsy performed from the inside of the colon by a co-

lon-targeted pseudobezoar which will be in contact with

the colonic walls in a friction-like fashion severe enou gh

to collect tissue samples, but moderate enough not t o cause

excessive or abnormal bleeding or mucosal damage. This

“artificial stool” will enable generalized biopsy from the

entire organ (without actually having the information

from which exact location in the organ the tissue samples

have been collected). The advantage of having it screen

the entire organ is to overcome the miss of adenomas in

the right side of the colon as attested by Schoenfeld in

[28], who calls for improvements in colonoscopy.

A recent patent application close to what we propose

has already been filed [29]. It discloses a colon-targeting

ingestible device platform designed to recognize its entry

to the colon and expand in the colon, ultimately aiming at

improved imaging of the colon walls. On approaching

the external anal sphin cter muscle, the ingestible p ill may

contract or deform, for elimination. Colon recognition

may be based on a structural image, based on the differ-

ences in diameters between the small intestine and the

colon, and particularly, based on the semilunar fold

structure, which is unique to the colon. Additionally or

alternatively, colon recognition may be based on a func-

tional image, based on the generally inflammatory state

of the vermiform appendix. Addition ally or alternatively,

pH, flora, enzymes and/or chemical analyses may be

used to recognize the colon. The imaging of the colon

walls may be functional, by nuclear-radiatio n imaging of

radionuclide-labeled antibodies, or by optical-fluores-

cence-spectroscopy imaging of fluorescence-labeled an-

tibodies. Additionally or alternatively, it may be struc-

tural, for example, by visual, ultrasound or MRI means.

Due to the proximity to the colon walls, the imaging is

claimed to be advantageous to colonoscopy or virtual

colonoscopy, as it is designed to distinguish malignant

from benign tumors and detect tumors even at their in-

cipient stage. Various sensors are envisioned to be em-

bedded within the expandable colonic structure, includ-

ing e.g. radioactive-emission detectors, fluorescence de-

tectors, ultrasound detectors, MRI detectors, still and

video cameras operating in the visible and/or infrared

light ranges, temperature detectors, and impedance de-

tectors.

Recently offered patent pending technology [30], also

offers a colon-targeting expandable structure, but it has 4

distinct features: 1)Its expansion is facilitated by a per-

meable, mesh-like gauze structure which is in constant

contact with the walls of the colon; 2) The expansion is

provided by swellable granules of an appropriate bio-

compatible polymer (e.g. polyacrylic acid) which swell

individually but do not fuse into each other, thus not

forming a uniform mass non-permeable to gases and liq-

uids causing colonic obstruction; 3) The design of the

entire device is such that the mesh-like gauze structure

can exert relatively constant pressure on the colonic

walls from the moment it reaches its final dimensions,

until it exits the organ, thus enabling abrasive contact

(for scraping maximally well the colonic walls while

retaining the scraped material within the structure, with-

out, however, damaging the colonic walls); 4) This tech-

nology aims at collecting samples of tissue and bodily

fluids, to be expelled from the body and analyzed later,

rather than detecting colon pathologies in situ via detec-

tors as disclosed in the cited US Patent Application

20050266074 [29];

The aim of the technology is creating a controllable,

organ-targeting gastrointestinal pseudobezoar with the

purpose to scrape the organ from inside in order to col-

lect maximal diagnostic information for further process-

ing. The implement can be self-administrable (in the case

of humans) or administrable autonomously or unaided,

meaning the implement is administrable in a non-inva-

sive fashion, without the need of any external positioning

or manipulating device functionally attached to it, such

as an endoscope.

When the container has the first dimension, the im-

plement can be retained in a capsule capable of being

easily swallowed or administered autonomously. Once

the capsule has dissolved and the container is released in

the colon, the colonic fluids will enter the fluid-perme-

able, mesh-like, expandable container. When the fluid

contacts the at least one swellable molecule cluster, the

cluster will swell and the container will expand to the

second dimension. When the container has expanded to

the second dimension, it is sufficiently large so as to

touch the colonic walls. The number of swellable mole-

cule clusters in the container, their individual diameter,

and their liquid-retaining and absorbing properties under

various pressures, as well as the design of the container

itself are made such that the swollen implement has an

appropriate compliance to remain in constant touch with

the colonic walls regardless of the lumen of the organ.

For example, in a section of the colon where the lumen is

large, the implement expands in a spherical shape to

touch the walls of the organ. When the lumen of the co-

lon is reduced, the implement elongates itself longitudi-

nally in the organ, but it remains in contact with the

colonic walls.

O. YADID-PECHT, M. P. MINTCHEV 13

An initial implementation of such a p seudobezoar was

administered inchronic dogs. Two dogs had been given 6

pills per day for a month. Figure 1 depicts the pseudo-

bezoar as it has left the colon. No intestinal obstructions

have been reported during the entire duration of the tests.

Further tests need to be carried to prove safety, but the

initial testing had proven encouraging and we intend to

continue to a second stage of chronic animal testing to

demonstrate safety on a larger experimental sample.

Prospects include having this technology be competitive

with current preferred screening technology of choice,

which is assessed in [31] to be FOBT.

A recent debate was presented as to whethercolono-

scopy is still the preferred screening method for colon

cancer [28]. Indeed it seems that both physicians agree

that that is the case for now. However it would be inter-

esting to quote Dr. Schoenfield, “The “preferred” test for

colorectal cancer (CRC) is not colonoscopy… in the fu-

ture” [28].

4. Additional Prospects and Conclusion

We envision the utilization of the pseudobezoar technol-

ogy for therapy as well. Fecal transplants are new ther-

apy methods that are gaining more popularity although

they involve the administration of feces from healthy

subjects to the colons of patients suffering from a variety

of disorders, such as infection with Clostridum Difficile

bacteria [32]. The techniques used for administering such

fecal transplants are invasive, and therefore, uncomfort-

able for patients. The futuristic prospect is to use the

pseudobezoar platform for administering fecal trans-

plants in a non-invasive way, via an ingestible pseudo-

bezoar, impregnated with the bacteria to be served.

Figure 1. An image of thepseudobezoar as it has left the

colon of a dog. All dimensions are in cm.

In conclusion, a new technology which can serve as an

alternative to wide spread colon screening methods was

described. Possibilities exist for a pseudobezoar-based

medical device for colon cancer screening, early diagno-

sis of polyps, and even for bacterial transplant therapy.

We have described early results pertaining to the safety

of the implant in dogs. Efficacy over alternative screen-

ing methods and therapy is yet to be demonstrated. It

appears that the pseudobezoar technology carries great

promise both as medical diagnostic and therapeutic de-

vice and we look forward to describe new successes in

this new area of medical device development in the near

future.

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