Cholangioscopy and pancreatoscopy

INTRODUCTION — Miniature endoscopes and catheters have been developed that permit direct visualization of the bile and pancreatic ducts (collectively known as cholangiopancreatoscopy [CP]). These endoscopes and catheters are passed through the working channel of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP).

The first optical choledochoscope was described in 1941 [1], and the peroral approach was subsequently introduced in the early 1970s [2,3]. Continued refinements have resulted in commercially available small-diameter cholangiopancreatoscopes that include working channels and the ability to deflect the tip of the scope [4-6].

This topic will review cholangioscopy and pancreatoscopy performed during ERCP using commercially available instruments. An overview of ERCP and alternate approaches for direct bile duct visualization are discussed elsewhere. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults" and "Percutaneous transhepatic cholangioscopy".)

INDICATIONS — Cholangioscopy is primarily used for the treatment of difficult bile duct stones (image 1 and picture 1) and for the evaluation of indeterminate biliary strictures (ie, strictures that could not be diagnosed as being benign or malignant with sampling techniques such as brush cytology or biopsy) (image 2 and image 3 and image 4 and picture 2 and picture 3) [7-18]. During cholangioscopy, targeted biopsies of bile duct lesions can be obtained (picture 4). Cholangioscopy can also be used to evaluate equivocal fluoroscopy findings during endoscopic retrograde cholangiopancreatography (ERCP), to assess the extent of cholangiocarcinoma prior to surgery, and to identify stones not seen by conventional cholangiography. In one series that included patients with primary sclerosing cholangitis, 30 percent had stones that had been missed by cholangiography [11].

During cholangioscopy, bile duct stones can be fragmented using electrohydraulic or laser lithotripsy probes, and these techniques are discussed in more detail separately. (See "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones" and "Laser lithotripsy for the treatment of bile duct stones".)

Similarly, pancreatoscopy is used for evaluating pancreatic strictures (image 5) and pancreatic duct dilation to exclude intraductal papillary mucinous neoplasms (IPMN) (picture 5) and for the treatment of symptomatic main pancreatic duct stones (picture 6 and picture 7 and picture 8 and image 6) [6,13-15,19]. (See 'Efficacy' below.)

EQUIPMENT — Systems for cholangiopancreatoscopy (CP) were initially endoscope-based systems, commonly referred to as "mother-daughter" systems. However, such systems are no longer commercially available and have been replaced by a catheter-based system (SpyGlass II Direct Visualization System):

●Catheter-based system – The catheter-based system is digital, is marketed in the United States to be single use, and is designed for use by a single endoscopist [20,21]. However, in countries where the system is reused, two endoscopists perform the procedure and control the duodenoscope and cholangiopancreatoscope with the goal of limiting trauma to the device [22]. The system is 10.5 French, with a 1.2 mm working channel and two 0.6 mm lumens for dedicated water irrigation. The tip of the catheter can be deflected in four directions (up-down and left-right).

●Other equipment options – Cholangioscopy can also be performed using a slim gastroscope in patients with a dilated common bile duct, but stability within the duct is difficult, and thus, the use of this approach is limited.

Slim gastroscopes have diameters of 5 to 6 mm, and thus, they can only be used in patients with dilated common bile ducts [13,23]. If a gastroscope is being used, insufflation should be with saline, water, or carbon dioxide because air insufflation has been associated with air embolism [24,25]. The advantage of using a slim gastroscope is that the video image quality is superior and may include narrow band imaging capability (picture 9). In addition, the working channel is larger and can accommodate argon plasma coagulation probes, larger biopsy forceps, and larger lithotripsy fibers.

PATIENT PREPARATION

Diet — Prior to endoscopic retrograde cholangiopancreatography (ERCP), patients typically take no food by mouth for four to eight hours and sometimes longer if there is known or suspected delayed gastric emptying [26]. Alternatively, clear liquids can be taken up to two hours before elective procedures requiring general anesthesia or sedation/analgesia [27].

Medications — Most medications can be continued up to the time of endoscopy and are usually taken with a small sip of water. Some medications may need to be adjusted prior to upper endoscopy, such as medications for diabetes, due to decreased oral intake around the time of the procedure.

Management of anticoagulants — Many patients undergoing cholangioscopy or pancreatoscopy will require a sphincterotomy. For patients on anticoagulants and/or nonaspirin antiplatelet agents who undergo endoscopic sphincterotomy, the procedure-related bleeding risk is higher. The management of antiplatelet and anticoagulant therapy in patients undergoing endoscopic sphincterotomy is typically individualized, is managed in conjunction with the prescribing specialist, and is discussed separately. (See "Management of anticoagulants in patients undergoing endoscopic procedures" and "Management of antiplatelet agents in patients undergoing endoscopic procedures" and "Gastrointestinal endoscopy in patients with disorders of hemostasis".)

Antibiotic prophylaxis — Guidelines regarding the use of antibiotics in patients undergoing endoscopic procedures do not specifically address antibiotic prophylaxis for cholangioscopy or pancreatoscopy. However, preprocedural antibiotic prophylaxis has generally been given to all patients due to a potentially higher rate of cholangitis compared with patients undergoing ERCP without cholangioscopy [28-30]. The antibiotic regimens in this setting are similar to those used for patients undergoing ERCP who require antibiotic prophylaxis (table 1). Antibiotic prophylaxis is also given to patients undergoing pancreatoscopy, especially in the setting of obstructing pancreatic duct stones. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures".)

PROCEDURE

Sedation/anesthesia — General anesthesia or monitored anesthesia care is typically utilized for patients undergoing cholangiopancreatoscopy (CP) because the procedure times are longer compared with standard endoscopic retrograde cholangiopancreatography (ERCP), and fluid irrigation to enhance intraductal visualization can lead to pooling within the stomach, increasing the risk of aspiration [31]. (See "Anesthesia for gastrointestinal endoscopy in adults".)

Technique

Cholangiopancreatoscope insertion — CP is carried out during ERCP. Lesions and suspicious areas identified during initial ERCP can be mapped with spot radiographs to aid with subsequent localization using CP. Sphincterotomy and/or stricture dilation are performed as needed to facilitate scope passage [31]. Cholangiopancreatoscopes are passed through the 4.2 mm working channel of a therapeutic duodenoscope. Following ERCP-directed guidewire access to the common bile duct or pancreatic duct (and usually followed by sphincterotomy), the cholangiopancreatoscope is advanced over the guidewire and into the duct using a combination of endoscopic and fluoroscopic guidance (image 7). If a slim gastroscope is being used, it may be inserted into the duct over a guidewire placed during ERCP or by using a freehand technique [32].

Once the scope is advanced to the target location, the guidewire (if used) can be removed to permit use of the working channel and to enhance visualization.

Factors that may limit passage of a cholangiopancreatoscope include a narrow duct diameter and tight strictures.

Intraductal lithotripsy — Electrohydraulic lithotripsy (EHL) can be used to treat both bile duct (picture 1 and picture 10 and image 8) and pancreatic duct stones. Visualization with CP during intraductal lithotripsy helps to avoid duct injury. The EHL fiber contains two coaxially insulated electrodes ending at an open tip. During saline immersion, sparks are generated that produce high-amplitude hydraulic pressure waves for stone fragmentation [33]. The tip of the EHL fiber should protrude no more than 2 to 3 mm from the scope and be positioned en face with the stone approximately 1 mm away while the generator's foot pedal is depressed to deliver energy [31]. The technique for EHL is discussed in more detail separately. (See "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones".)

An alternative to EHL is pulsed holmium laser lithotripsy. During laser lithotripsy, a laser beam is transmitted via a flexible quartz fiber through the working channel of the cholangiopancreatoscope (picture 7). The application of repetitive pulses of laser energy to the stone leads to the formation of a gaseous collection of ions and free electrons of high kinetic energy. This plasma vacuum rapidly expands as it absorbs the laser energy and then collapses, inducing a spherical mechanical shock wave between the laser fiber and stone, leading to stone fragmentation [34]. (See "Laser lithotripsy for the treatment of bile duct stones".)

Intraductal biopsy — Two methods can be used to obtain targeted biopsies from the bile or pancreatic duct:

●CP-directed biopsy – CP-directed biopsy is performed by passing a miniature CP biopsy forceps through the working channel under direct endoscopic visualization.

●CP-assisted biopsy – For CP-assisted biopsy, the target site is localized using CP visualization and fluoroscopic spot films, with the tip of the cholangiopancreatoscope positioned at the lesion. After removing the cholangiopancreatoscope, a conventional biliary biopsy forceps or pediatric forceps is then passed through the working channel of the duodenoscope to obtain tissue samples under fluoroscopic guidance [10].

EFFICACY

Bile duct stones — Cholangioscopy with electrohydraulic lithotripsy (EHL) or laser lithotripsy is effective for removing bile duct stones that cannot be extracted with conventional endoscopic retrograde cholangiopancreatography (ERCP) techniques (eg, sphincterotomy followed by stone removal with a balloon catheter). (See "Endoscopic management of bile duct stones", section on 'ERCP-guided stone removal'.)

Bile duct clearance rates ranging from 85 to 100 percent have been reported [35-39]. Cholangioscopy has also been used to remove residual stone fragments after ERCP with mechanical lithotripsy, with a clearance rate of 85 percent in one small study [17]. (See "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones", section on 'Efficacy'.)

Intrahepatic stones (seen in the setting of recurrent pyogenic cholangitis) require more intensive endotherapy than bile duct stones. One study reported 36 patients with hepatolithiasis treated with peroral cholangioscopy-directed EHL or laser lithotripsy [40]. Despite a mean of 4.5 cholangioscopy sessions and adjunctive extracorporeal shock wave lithotripsy (ESWL) in one-third of the patients, ductal clearance was achieved in only 75 percent (64 percent complete, 11 percent partial clearance). After a mean of 7.8 years of follow-up, symptomatic recurrence developed in 22 and 25 percent of those with complete and partial clearance, respectively. In general, effective treatment of intrahepatic stones may require combined peroral and percutaneous approaches or surgical resection [41]. (See "Recurrent pyogenic cholangitis".)

Pancreatic stones — Completely or partially obstructing pancreatic duct stones causing an increase in intraductal pressure are implicated as a cause of chronic abdominal pain in patients with chronic pancreatitis. Either alone or as an adjunct to ESWL, peroral pancreatoscopy (POP)-guided lithotripsy may facilitate duct clearance. (See "Extracorporeal shock wave lithotripsy for pancreatic stones" and "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones", section on 'Pancreatic stones'.)

Data suggest that POP-guided lithotripsy was effective for clearing the pancreatic duct and improving symptoms (eg, abdominal pain) [42-46]. In a meta-analysis of 16 studies including 383 patients with pancreatic duct stones who had POP-guided lithotripsy, the pooled rates of pancreatic duct clearance and of symptomatic improvement were 76 and 77 percent, respectively [46]. Reported adverse events included post-ERCP pancreatitis (7 percent), abdominal pain (5 percent), fever (4 percent), perforation (4 percent), and bleeding (3 percent). In a series of 28 patients with chronic pancreatitis who underwent POP-guided laser lithotripsy for pancreatic duct stones, complete stone clearance was achieved in 22 patients (79 percent), and partial clearance was achieved in three patients (11 percent) [43]. After a median follow-up of 13 months, 25 patients (89 percent) reported improvement in pain and decreased opioid use.

Suspected biliary malignancy — For patients with indeterminate biliary strictures or filling defects (image 9), cholangioscopy permits direct inspection of the epithelium for subtle abnormalities or to obtain biopsies (picture 2 and picture 3 and picture 11). However, stent-associated changes and trauma related to stricture dilation may alter the mucosal appearance, making visual diagnosis more challenging.

Visualization with cholangioscopy appears to enhance diagnostic accuracy by detecting "tumor vessels" (irregularly dilated and tortuous blood vessels) in patients with suspected malignancy, but data from randomized trials have been limited (picture 12 and picture 9) [47,48]. In general, several features including intraductal nodules or masses, an infiltrative or ulcerated stricture, "tumor vessels" (dilated, tortuous vessels), or papillary or villous mucosal projections may indicate malignancy and should prompt obtaining biopsies [49].

Data from small trials and observational studies suggest that peroral cholangioscopy is useful for differentiating malignant from benign biliary lesions [10,12,16,47,48,50-55]. In a trial including 60 patients with indeterminate hilar biliary strictures on magnetic resonance cholangiopancreatography (MRCP), tissue sampling using single-operator cholangioscopy guidance had higher sensitivity compared with ERCP-guided brushings (68 versus 21 percent) [48]. Limitations to this trial included lack of fluoroscopy-guided biopsies, number of ERCP-guided brushings (six), and use of MRCP to establish the presence of indeterminate stricture. In a meta-analysis of eight studies including 337 patients who had peroral cholangioscopy for indeterminate biliary lesions, visual inspection was 90 percent sensitive and 87 percent specific for diagnosing malignancy [55]. Biopsies performed during cholangioscopy had a sensitivity and specificity of 69 and 98 percent, respectively. In a subsequent multicenter study including 89 patients with indeterminate bile duct lesions, visualization with cholangioscopy was 95 percent sensitive and 93 percent specific for diagnosing malignancy, while cholangioscopy-directed biopsies had a sensitivity of 65 percent and a specificity of 89 percent [54].

It should be noted that confirming malignancy in the sclerotic type of cholangiocarcinoma can be difficult because malignant cells are often absent on superficial mucosal biopsies as the result of a fibrotic reaction to the tumor and expansion into the subepithelial layers.

Cholangioscopy has been combined with narrow band imaging at select referral centers in Japan and the United States, and the addition of this technology may enhance mucosal and tumor vessel visualization. Combining cholangioscopy characteristics such as infiltrative stricture and "tumor vessels" increases sensitivity in detecting malignancy to nearly 90 percent; however, such systems are not commercially available [56,57].

Primary sclerosing cholangitis — The role of cholangioscopy in evaluating patients with primary sclerosing cholangitis (PSC) for malignancy is limited. However, the diagnosis may be challenging when using only cholangiography or tissue sampling. In a prospective study of 53 patients with PSC, adding direct visualization with cholangioscopy increased the diagnostic yield compared with ERCP alone [58]. Twelve patients (23 percent) had cancer, and 41 patients (77 percent) had benign disease. Compared with cholangiography, cholangioscopy had higher sensitivity (92 versus 66 percent), specificity (93 versus 51 percent), and negative predictive value (97 versus 84 percent). However, this yield has not been duplicated by other centers, and traditional malignant features seen on cholangioscopy, such as nodular and infiltrative strictures, may be also present in patients with benign PSC [11].

Suspected pancreatic neoplasm — Due to the relatively narrow caliber and tortuous segments of the pancreatic duct, intraductal inspection may be limited. For example, a minimum duct diameter of 4 mm (and ideally 5 mm) is generally required to perform POP. For patients with suspected intraductal papillary mucinous neoplasm (IPMN) or other pancreatic tumors, POP can evaluate the extent of disease and provide a histopathologic diagnosis. In addition, POP may have a role in identifying IPMN in patients with a dilated pancreatic duct in the setting of presumed idiopathic chronic calcific pancreatitis [59,60]. For IPMN, identifying main pancreatic duct lesions is important as the risk of high-grade dysplasia or malignancy is higher than it is with side-branch lesions alone [61]. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Pathophysiology and clinical manifestations" and "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Evaluation and management".)

For distinguishing benign from malignant IPMN, the endoscopic findings that correlated with malignancy included fish egg-like projections with prominent vasculature, villous protrusions, and vegetative protrusions, with a sensitivity and specificity of 68 and 87 percent, respectively, and with lower sensitivity for branch-type compared with main duct lesions [62]. Several studies have compared POP with intraductal ultrasound (IDUS), computed tomography (CT), endoscopic ultrasound (EUS), and pancreatography for distinguishing benign from malignant IPMN lesions [62-66]. The finding of 3 to 4 mm projections on pancreatoscopy of main duct IPMN lesions has a sensitivity for malignancy of 67 to 100 percent compared with 16 to 32 percent for CT, 56 to 100 percent for IDUS, and 55 to 92 percent for EUS [62-64]. A combination of pancreatoscopy and IDUS may improve the ability to identify the longitudinal and transmural spread of pancreatic malignancies. (See "Intraductal ultrasound for evaluating the pancreaticobiliary ductal system".)

POP has been studied for evaluating indeterminate pancreatic pathology [67,68]. In a case series including 79 patients with pancreatic stricture or dilated pancreatic duct, the diagnosis of neoplasia was established with POP-guided tissue sampling in 29 of 33 patients (88 percent) [68]. In addition, the sensitivity and specificity for detecting neoplasia with POP visualization were 87 and 86 percent, respectively. Another study that included 115 patients with a minimum two-year follow-up found that pancreatoscopy detected 63 percent of pancreatic cancers, 80 percent of benign strictures, and 95 percent of IPMN lesions [67]. Neoplasia assessment was based upon the presence of coarse mucosa, submucosal protrusion, friability, tumor vessels, and papillary projections.

ADVERSE EVENTS — Adverse events associated with peroral cholangioscopy and pancreatoscopy are often associated with specific maneuvers performed during endoscopic retrograde cholangiopancreatography (ERCP; eg, sphincterotomy). (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Adverse events'.)

Adverse events specific to the performance of cholangiopancreatoscopy (CP) include cholangitis, which is related to intraductal fluid irrigation, pancreatitis in the setting of pancreatoscopy, and, uncommonly, hemobilia and bile leaks attributable to intraductal lithotripsy [9,28,44,45,69]. The rate of post-ERCP pancreatitis and/or abdominal pain flare-up after pancreatoscopy has ranged from 7 to 20 percent, with most series reporting cases that were mild or moderate in severity [44-46]. Our center retrospectively assessed patients undergoing ERCP with or without CP and found that ERCP with CP may be associated with a higher rate of procedure-related complications than ERCP alone [28]. This increased risk was observed in overall complications (7.0 versus 2.9 percent), consensus complications (pancreatitis, perforation, cholangitis, or bleeding; 4.2 versus 2.2 percent), and specifically with postprocedural cholangitis (1.0 versus 0.2 percent) [28].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gallstones".)

SUMMARY AND RECOMMENDATIONS

●General principles – Miniature digital catheters have been developed that permit direct visualization of the bile and pancreatic ducts (cholangioscopy and pancreatoscopy, respectively). These are passed through the working channel of a standard therapeutic duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). (See 'Introduction' above.)

●Cholangioscopy – Cholangioscopy with intraductal lithotripsy has become an established modality in the treatment of difficult biliary stones. When used in the evaluation of indeterminate biliary strictures by endoscopists experienced in recognizing intraductal pathology, it increases the diagnostic yield of tissue sampling. (See 'Indications' above and 'Bile duct stones' above and 'Suspected biliary malignancy' above.)

●Pancreatoscopy – Pancreatoscopy is complementary to other imaging modalities in the evaluation of intraductal papillary mucinous neoplasms of the pancreas and is emerging as a sole or adjunctive therapy to extracorporeal shock wave lithotripsy for the treatment of main pancreatic duct stones. It remains investigational in the diagnosis of pancreatic adenocarcinoma. (See 'Indications' above and 'Pancreatic stones' above and 'Suspected pancreatic neoplasm' above.)

●Adverse events – Adverse events specific to the performance of cholangiopancreatoscopy include cholangitis, which is related to intraductal fluid irrigation, pancreatitis in the setting of pancreatoscopy, and, uncommonly, hemobilia and bile leaks attributable to intraductal lithotripsy. (See 'Adverse Events' above.)