New Methods & IV aterials
`
`Endoscopic retrograde wire-guided cytol
`ogy of malignant biliary strictures using
`a novel scraping brush
`
`Vinod K. Parasher, MD
`Kees Huibregtse, MD, PhD
`
`Background: Tissue sampling to differentiate
`benign from malignant pancreatobiliary strictures
`remains problematic despite the availability of sev
`eral new sampling methods. A new device is
`described which attempts to correct some of the
`drawbacks.
`Methods: The device consists of a 10F dilator
`which has an attached pad of Velcro. The Velcro
`has semi-rigid, mushroom-shaped bristles. A cyto
`logic sample is obtained by the abrasive action of
`the brush when it is passed through the stricture.
`Fifteen patients with obstructive jaundice under
`went brushing of the bile duct using this device.
`Results: Cytologic samples obtained with this
`device were positive for malignancy in all 15
`patients. Diagnostic confirmation was obtained by
`assessment of clinical course, radiologic findings,
`and during surgery.
`Conclusion: Preliminary experience indicates that
`this new device enhances the yield of tissue sam
`pling from malignant bile duct strictures.
`
`Tissue sampling to differentiate benign from
`malignant pancreatobiliary strictures remains
`imperfect despite recent advances in instrumenta
`tion and techniques. Single sampling techniques
`used during ERCP are associated with relatively
`low and varying yields ranging from 37% to 71%. 1"5
`A combination of different techniques, however,
`improves the overall sensitivity.
`
`Received July 23, 1997. For revision January 13, 1998. Accepted
`April 24, 1998.
`
`From the Department of Medicine, Beebe Medical Center, Lewes,
`Delaware; and the Academic Medical Center, Amsterdam, The
`Netherlands.
`
`Presented in part at the annual meeting of the American Society
`of Gastrointestinal Endoscopy, May 1996, San Francisco,
`California (Gastrointestinal Endoscopy 1996:43:300).
`
`Reprint requests: Vinod K. Parasher, MD, Director of Endoscopy,
`Beebe Medical Center, 424 Savannah Road, Lewes, DE 19958.
`
`Copyright © 1998 by the American Society for Gastrointestinal
`Endoscopy
`
`0016-5107/98/S5.00 + 0 37/69/91389
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`The factors responsible for these inconsistent
`results include the extrinsic nature of the malig
`nancy, submucosal penetration of the tumor without
`involvement of the ductal epithelium, inaccessibility
`of the lesion because of accompanying fibrosis, and
`the scirrhous nature of the tumor. However, the
`yield of cytology increases when the ductal epitheli
`um is breached. Subsequently, the tumor becomes
`more accessible as observed during the application
`of sampling techniques, such as fine-needle aspira
`tion, forceps biopsy, and dilation of the strictures
`before brushings.
`Although present cytology brushes breach the
`epithelium to some extent, the soft nature of the
`bristles and the absence of adequate radial force
`directing the bristles into the epithelium reduce the
`frequency of a positive result. Variations in brush
`design such as differences in length and width of the
`bristles may also contribute to suboptimal acquisi
`tion of specimens. Conceivably,
`if a stricture is
`scraped by an abrasive device whose diameter is
`greater than the diameter of the stricture, sufficient
`accessibility, mucosal penetration, and disruption of
`the ductal epithelium could be achieved; and, if so,
`yields would be enhanced. Indeed, scraping by stent
`"flaps"8'9 and more recently by means of Soehendra
`stent retrievers10 seems to achieve some of the
`desired results. In this article we describe our expe
`rience with a new device that is used as a scrap
`ing/abrasive brush to obtain cytology from biliary
`strictures.
`
`METHODS
`
`The device consists of a 10F tapered dilator. In close
`proximity to the dilator is a 1 cm pad of Velcro consisting
`of specially designed semi-rigid, mushroom-ended bristles
`that are glued with a nontoxic adhesive and mounted over
`a 200 cm 4F inner catheter (Fig. 1). The assembly (except
`the dilator) is housed in a 7F Teflon outer sheath that pro
`tects the acquired cellular material (Fig. 2). Radiopaque
`markers are provided proximal and distal to the pad and
`also on the outer Teflon sheath to enhance fluoroscopic
`visualization.
`When initiating the procedure the device is passed over
`a previously placed 0.035-inch guidewire. The stricture is
`dilated by gently pushing the 10F dilator through it. The
`brushings and scrapings are then taken by deploying the
`device through the stricture and then pulling it into the
`outer sheath which is placed at the lower end of the stric
`ture. Multiple maneuvers are carried out to enhance
`acquisition of cytologic material. A sphincterotomy is not
`required to accomplish this procedure. After completion of
`the procedure, the brush is retrieved over the guidewire.
`The short end of the device (including the sheath) is cut,
`and the contents are expressed into a centrifuge tube that
`is suspended with cytology transport media. The brush
`and sheath are spun using a vortex agitator to dislodge
`
`288 GASTROINTESTINAL ENDOSCOPY
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`VOLUME 48, NO. 3, 1998
`
`EXHIBIT 1004
`
`

`
`ERCP wire-guided cytology with novel scraping brush
`
`V Parasher, K Huibregtse
`
`i
`
`Figure 1. Scraping brush consisting of 10F tapered dilator
`{small arrow) and Velcro pad with the radiopaque markers
`located proximal and distal to it (arrowhead).
`
`Figure 2. Nondeployed scraping brush housed in 7F outer
`Teflon sheath ( large arrow).
`
`the cellular material. The fluid is processed with cytospin,
`and slides can be made for appropriate staining. Manual
`disengagement of the material from the Velcro brush is
`also performed by using a needle, and the materials are
`used for cell block. Velcro, by virtue of its intrinsic proper
`ty of adherence, gathers a large quantity of cellular mate
`rial. No loss of cellular material occurs during the process
`of withdrawal because the brush fits snugly into the outer
`sheath and no movement of the brush takes place in the
`outer sheath because its diameter (7F) is less than that of
`the brush (9F).
`
`Patients
`
`Fifteen patients aged 55 to 78 years (mean age 68.3
`years, 3 men and 12 women) who were referred for evalu
`ation of obstructive jaundice participated in the study.
`Informed consent was obtained from all participants.
`Brushings were taken by means of
`the previously
`described technique in a nonconsecutive fashion.
`Confirmation of the diagnosis was obtained by assess
`ment of the clinical course, invasive radiology, or surgery.
`
`In four patients brushings were additionally taken using
`the Geenen cytology brush (Wilson-Cook Medical, Inc.,
`Winston-Salem, N.C.) before using the new device. No
`patients underwent dilation before the passage of the new
`device. In addition, none of the patients had prior stents
`or had undergone previous attempts at endoscopic sam
`pling. The device was deployed only in the bile duct.
`
`RESULTS
`
`Cytology was positive in all patients. There were
`1 1 cases of pancreatic carcinoma, 2 of cholangiocar-
`cinoma, 1 of Klatskin tumor, and 1 case of metasta
`tic disease. When the cytology material obtained
`from the Geenen brush and our scraping brush was
`compared, the amount of cellular material obtained
`with this new device was at
`least
`twice that
`obtained with the current standard brush. This com
`parison was made by manually counting the cellular
`material. Some degree of cell injury was noted as the
`
`VOLUME 48. NO. 3, 1998
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`GASTROINTESTINAL ENDOSCOPY 289
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`

`
`V Parasher, K Huibregtse
`
`ERCP wire-guided cytology with novel scraping brush
`
`result of the abrasion. However, this did not impair
`the ability to make a definitive diagnosis. No brush-
`or procedure-related complications occurred. No
`patients with positive cytology were later shown to
`have a benign stricture.
`
`DISCUSSION
`
`A definitive histologic diagnosis of pancreatobil-
`iary strictures is crucial in the diagnosis and man
`agement of patients who present with malignant
`obstructive jaundice. This is important for patient
`prognosis and peace of mind inasmuch as the clini
`cal presentation by itself can be confusing. In two
`studies, 10% of hilar tumors were shown to be
`benign even though the preoperative diagnosis was
`malignancy.12'13 Several modalities have been used
`for tissue acquisition. Brush cytology is popular and
`has a sensitivity that varies from 35% to 70%.1-6 A
`review of 6 studies of brush cytology found a sensi
`tivity of 59% and specificity of 99%.3 The yield of
`brush cytology is variable, and a relatively poor
`yield may be due in part to the scanty nature of the
`specimen coupled with the extrinsic/desmoplastic
`nature of the tumor. Furthermore, the soft bristles of
`currently available brushes may not penetrate deep
`enough (or breach the ductal epithelium sufficient
`ly) to gain access into the tumor. Perforation may
`also occur.4
`Forcep biopsies can obtain deeper tissue speci
`mens; the sensitivity varies from 14% to 71%.6'7
`However, this requires sphincterotomy and is tech
`nically difficult. Complications such as perforation
`may occur.5 Needle biopsies can also reach deeper
`tissue layers and are reported to have yields of 37%
`to 62%.5'6 Combinations of the above methods are
`superior to single methods.4"7 One large prospective
`study involving 233 consecutive patients found a
`sensitivity for brush cytology of 35% and 43% for
`biopsy. When combined, the sensitivity was 63% and
`specificity 97%. 5
`We have described a new device which, by virtue
`of its design, corrects some of the drawbacks of cur
`rently used conventional brushing devices. The fea
`tures of this scraping brush that may result in high
`er yields from malignant biliary strictures include
`the following: (1) The 10F tapered dilator dilates the
`stricture and causes disruption of the mucosa; dila
`tion of the stricture before obtaining the cytology
`specimen has been shown to increase yield.11 (2) The
`9F diameter of the actual brush may allow a snug fit
`within the stricture thus generating sufficient radi
`al penetrating force during movement of the brush
`to further disrupt
`the ductal epithelium.
`(3)
`Scraping with this device is achieved by the special
`ly designed Velcro pad, which is abrasive. Because
`
`the bristles are semi-rigid and rough (when com
`pared with the relatively flexible and soft pliable
`bristles of a standard brush) and tightly woven into
`a fabric, this combination of characteristics could
`have
`generated
`additional
`scraping
`force.
`Furthermore, because of the intrinsic adhesive
`nature of the Velcro, significant amounts of cellular
`material become attached to its surface. This pro
`vides greater numbers of cells which are not easily
`dislodged. The combination of these features may
`have contributed to the improved results obtained
`with the use of this device. Prospective studies are
`needed to compare the use of this device with other
`existing methods.
`
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`
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`290 GASTROINTESTINAL ENDOSCOPY
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`VOLUME 48, NO. 3, 1998