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Endoscopic retrograde cholangiopancreatography versus endoscopic ultrasound for tissue diagnosis of malignant biliary stricture: systematic review and meta-analysis.
Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis.
Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis.
Hence, different approaches to obtain tissue are being developed. Peroral cholangioscopy allows direct visualization of the biliary tract and targeted biopsies of the suspected area. However, recent studies still show moderate sensitivity, mostly because of the small opening diameter of the cholangioscopic forceps.
Because of these insufficient outcomes, alternative methods are necessary to increase the sensitivity and diagnostic rate.
Cryobiopsy Technique
The cryobiopsy technique is a new method for tissue extraction, which allows for extraction of high tissue amounts with a minimal diameter endoscopic instrument. It is already used in pneumology in clinical routine.
Carbon dioxide (CO2) flows with high pressure from the gas supply to the tip of the cryoprobe. At the probe tip, the gas expands internally through a small nozzle. The pressure difference caused by the CO2 expansion leads to a strong temperature decrease that cools the surrounding cryoprobe tip. The rapid cooling leads to an adhesion effect between the cryoprobe and surrounding tissue. The cryoprobe can subsequently be plucked, removing the attached tissue (Video 1, available online at www.giejournal.org).
Gas flow is regulated through a cryosurgical unit, and the activation time, and thereby the adhesion area, is controlled through a foot switch (Fig. 1). Higher activation times lead to an increased biopsy size.
Figure 1A, Cryo device with cart. B, Cryo device and instrument setting (effect 1, probe length 1150 mm). C, Cryoprobe tip (diameter 1.1 mm).
Significantly larger tissue samples were obtained with cryobiopsy compared to forceps biopsies. Furthermore, cryobiopsy was superior in histologic assessment quality and concerning tissue representativity.
In this study, for the first time in a human, we demonstrate the cryobiopsy technique in the bile duct during direct cholangioscopy.
Materials and Methods
The SpyGlass Discover Digital Catheter (Boston Scientific, Marlborough, Mass, USA) was used to visualize the bile duct stricture via direct percutaneous cholangioscopy. It has a working length of 65 cm and an accessory channel width of 1.2 mm (3.6F). The cryoprobe (ERBE, Marietta, Ga, USA) has a diameter of 1.1 mm and a length of 1150 mm and is operated by the cryosurgical device ERBECRYO 2 (ERBE).
SpyBite Max cholangioscopic forceps (Boston Scientific) were used to perform comparative forceps biopsies. Five forceps biopsies were performed in a “bite-on-bite” fashion.
Step-by-Step Setup and Operation of Cryobiopsy
1.
Connect cryoprobe with the cryosurgical unit. No setting needs to be adapted because only 1 setting is provided (effect 1).
2.
Ensure the CO2 bottle is connected to the cryo device and sufficient pressure is provided.
3.
A test activation is performed while the cryo probe is in water. If an ice ball formation is observed without gas bubbles, the probe can be used for biopsy retraction.
4.
Approach target tissue with cholangioscope.
5.
Attach cryoprobe to target tissue (probe can be positioned to the tissue either tangentially or perpendicular with the probe’s tip).
6.
The cooling is activated by continuously pressing the foot pedal.
7.
After 4 seconds, the cryoprobe and the cholangioscope together are pulled backward, plucking the tissue of the stricture. Note that the foot pedal needs to be continuously pressed to ensure a constant freezing and attachment of the tissue to the cryoprobe.
8.
The cryoprobe with the attached biopsy is transferred to a cup with normal saline solution at room temperature and deactivated. Within seconds the tissue detaches from the probe tip and can be transferred to a pathologic jar with formalin.
Case Report
A 41-year-old patient with longstanding ulcerative colitis and primary sclerosing cholangitis that had been diagnosed 27 and 14 years before, respectively, presented with symptoms of cholangitis and symptomatic stricture of the left hepatic duct. There was no evidence of cirrhosis or advanced fibrosis. The patient showed elevated bilirubin (2.8 mg/dL, upper limit normal [ULN]: 1.4), alanine aminotransferase (232 U/L, ULN: 50), and gamma-glutamyl transferase (326 U/L, ULN: 60). The CA 19-9 value was not elevated. Attempts of retrograde cannulation of the stricture were unsuccessful at 2 tertiary endoscopic centers, despite cholangioscopic visualization and use of different guidewires (Fig. 2). Because of a strong clinical suspicion of bacterial cholangitis within the left hepatic ductal system, percutaneous transhepatic biliary drainage (PTBD) was placed and the clinical condition of the patient improved significantly.
Figure 2A, Stricture of the left hepatic bile duct (arrow) and placement of percutaneous transhepatic biliary drainage. B, CT scan depicting the stricture (arrow) and prestenotic bile duct dilatation. C, Positioning of the cryobiopsy probe next to the biliary stricture (cholangioscopic view). D, Activation of the cryoprobe with ice formation providing attachment to the bile duct to obtain tissue by consecutive pulling of the probe (cholangioscopic view).
However, etiology of the biliary stricture had not been established, neither by transpapillary cholangioscopy-guided biopsies nor by percutaneous ductography. Therefore, 6 weeks after placement of PTBD, tissue retrieval from the stricture by cholangioscopy using a 1.1-mm mini cryoprobe was performed (Fig. 2, Video 1). In the same session, cholangioscopic forceps biopsies were performed in equivalent location as the cryobiopsies. The cryobiopsy obtained a markedly larger specimen compared with the cholangioscopic forceps biopsy, and inflammatory stricture caused by primary sclerosing cholangitis was diagnosed (Fig. 3). Consecutively, a double-pigtail plastic stent was placed and PTBD could be removed. No early or late adverse event was observed (follow-up at 3 months).
Figure 3A, Cholangioscopy-guided forceps biopsy specimen (SpyBite Max, Boston Scientific, Marlborough, Mass, USA; H&E, orig. mag. ×200). B, Cholangioscopy-guided cryobiopsy specimen (cryobiopsy probe, ERBE Elektromedizin GmbH, Tuebingen, Germany; H&E, orig. mag. ×200). C, Cholangioscopy-guided cryobiopsy specimen. Detailed view of cuboidal epithelium of the left hepatic bile duct (H&E, orig. mag. ×400).
In this case, cryobiopsy led to a successful clinical outcome with excellent tissue samples that enabled histology-based diagnosis of a critical bile duct stricture.
Direct visualization of indeterminate biliary strictures by cholangioscopy and targeted biopsies of the area of interest should intuitively provide the best possible diagnostic accuracy. However, sensitivity remains low and comparable to “blind” fluoroscopic-guided biopsies with a standard biopsy forceps.
This discrepancy can be explained by the small opening diameter of the cholangioscopic forceps, which leads to a smaller specimen. Also, the small cholangioscopic forceps has difficulty penetrating the dense epithelium of the bile duct, especially when there is only tangential access to the area of interest.
Studies in the pulmonary tract and recent ex vivo experiments in the bile duct show that cryobiopsy can overcome the challenge to provide representative biopsy specimens through a small endoscopic working channel. Cryobiopsy is therefore frequently used for tissue acquisition during bronchoscopy. The fact that the technique can be applied frontally and tangentially with equal efficacy is another advantage. This could be beneficial, especially in small bile ducts with limited room to angulate the cholangioscope.
However, several issues remain before cryobiopsy can be routinely applied in the bile duct. The cryoprobes used in the present study were approved for use in the bile duct; however, the intended use has been changed recently and restricted to the pulmonary tract. Therefore, further use in the bile duct must be considered off-label. Studies to approve the probe for use in the bile duct as well as in the urogenital tract are currently underway.
Furthermore, cryoprobes on the market are too short to use with conventional mother-baby cholangioscopes, such as SpyGlass DS (Boston Scientific). Therefore, longer cryoprobes, which fit the working channel of such scopes, must be developed for marketability. Moreover, systematic prospective clinical studies are required to compare the efficacy and safety of this cryobiopsy approach in comparison with cholangioscopy-guided forceps biopsies.
Conclusion
Cryobiopsy in the biliary system is a promising new technique that has the potential to overcome several disadvantages of cholangioscopic forceps biopsies. It might thereby improve the diagnostic work-up of indetermined biliary strictures in the future.
Disclosure
Ms Zimmermann, Dr Linzenbold, and Dr Enderle are employees of ERBE Elektromedizin GmbH, Tuebingen, Germany. Cryoprobes were provided by ERBE Elektromedizin GmbH, Tuebingen, Germany. All other authors disclosed no financial relationships.
Case description and video in cholangioscopic view demonstrating bile duct tissue acquisition by cholangioscopy-guided cryobiopsy technique.
References
De Moura D.T.H.
Moura E.G.H.
Bernardo W.M.
et al.
Endoscopic retrograde cholangiopancreatography versus endoscopic ultrasound for tissue diagnosis of malignant biliary stricture: systematic review and meta-analysis.
Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis.
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