DDW HIGHLIGHTS
Endoscopic retrograde cholangiopancreatography Jong Ho Moon, MD, PhD, Hyun Jong Choi, Yun Nah Lee Bucheon, Seoul, Korea
New technological developments in endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment have been slow to progress. However, several informative study results were presented during the 2014 Digestive Disease Week (DDW; 3–6 May; Chicago, Illinois, USA) in specific ERCP areas, such as prevention of post-ERCP pancreatitis using nonsteroidal antiinflammatory drugs and pancreatic duct stenting. Novel and interesting study results regarding preoperative stent selection for periampullary tumors, metal stents for hilar stricture or for prevention of duodenal reflux, and intraductal biliary tumor ablation using photodynamic therapy or radiofrequency ablation were discussed. Study results presented at the meeting regarding single-operator cholangioscopy using the SpyGlass system or direct peroral cholangioscopy have indicated the possibility of future development. Results using peroral pancreatoscopy and confocal laser endomicroscopy for biliary lesions, including strictures, were also presented.
POST-ERCP PANCREATITIS ERCP is used as a standard endoscopic procedure for the management of biliopancreatic lesions, even though it is an invasive procedure that may provoke adverse events. Therefore, trials aimed at minimizing complications should be conducted continually to improve safety. Post-ERCP pancreatitis (PEP) is still the most problematic adverse event associated with ERCP. However, pharmacologic Abbreviations: DDW, Digestive Disease Week; EBD, endoscopic biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; FCSEMS, fully covered SEMS; IPMN, intraductal papillary mucinous neoplasm; pCLE, probe-based confocal laser endomicroscopy; PEP, postERCP pancreatitis; POC, peroral cholangioscopy; POP, peroral pancreatoscopy; RCT, randomized, controlled trial; RFA, radiofrequency ablation; SEMS, self-expandable metallic stent; SOC, single-operator cholangioscopy. DISCLOSURE: All authors disclosed no financial relationships relevant to this article. This report is published simultaneously in the journals Gastrointestinal Endoscopy and Endoscopy. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy and ª Georg Thieme Verlag KG 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.07.004
388 GASTROINTESTINAL ENDOSCOPY Volume 80, No. 3 : 2014
prevention using nonsteroidal anti-inflammatory drugs and interventional prevention using pancreatic duct stenting have revealed significant improvements in the prevention of PEP. Administration of nonsteroidal anti-inflammatory drugs combined with prophylactic pancreatic duct stent placement may be ideal for preventing PEP. Kaplan et al.1 presented retrospective results of prophylactic rectal indomethacin combined with pancreatic duct stenting in 57 patients; these patients were compared with 285 patients who underwent pancreatic duct stenting alone, in order to determine the effects of each treatment on reducing the incidence and severity of PEP in patients undergoing manometry for suspected sphincter of Oddi dysfunction type 3. A single-dose indomethacin (100 mg) suppository was administered after ERCP. There were no statistically significant differences between the stent plus indomethacin group and the stent only group in terms of the incidence of PEP (18% vs. 23%), moderate-to-severe pancreatitis (9% vs. 7%), and the median duration of hospital stay (4 vs. 6 days). These results suggest that prophylactic rectally administered indomethacin combined with pancreatic duct stenting did not affect the incidence or severity of PEP when compared with pancreatic duct stenting alone in highrisk patients undergoing manometry, but further studies are warranted. In addition, the indomethacin dose and administration time necessary for the most effective prevention of PEP should be documented. Pancreatic duct stenting is an important method of preventing PEP, but there is still controversy regarding the ideal plastic stent, including its diameter, to be used for this purpose. A prospective multicenter, randomized, controlled trial (RCT) was conducted in patients at high risk of PEP, to investigate the rates of PEP and spontaneous distal migration when using unflanged, long-length, 3-Fr pancreatic duct stents compared with short-length, 5-Fr pancreatic duct stents.2 The 5-Fr stent was more efficacious than the 3-Fr stent in terms of spontaneous dislodgement rate and prevention of PEP among high-risk patients. These results suggest that the use of conventional 5-Fr pancreatic duct stents using a conventional 0.035-inch guidewire is a reasonable method for preventing PEP. However, continued stent development is needed to find more ideal stents for PEP prevention. In addition, the ideal stent length and rate of spontaneous dislodgement need to be determined. www.giejournal.org
Moon et al
BILIARY STRICTURES AND STENTS Histopathologic confirmation is critical for the management of biliary stricture, but acquisition of adequate endoscopic tissue for a definite diagnosis is not always successful. Probe-based confocal laser endomicroscopy (pCLE) is a new endoscopic diagnostic modality that allows real-time optical biopsy for immediate in vivo histology after positioning the probe in the area of interest. The probe can be delivered via a catheter during ERCP or via direct visualization using a cholangioscope. Several ongoing trials are investigating the diagnosis of biliary stricture using pCLE in order to overcome the issues surrounding current endoscopic tissue acquisition methods. Slivka et al3 reported interim study results from an international multicenter trial of the impact of pCLE on patients with indeterminate biliary strictures, according to a refined classification. The addition of pCLE increased the sensitivity to 89% compared with 82% using clinical history and ERCP alone. The specificity also increased from 71% to 79%. Tissue sampling combined with pCLE allowed an even greater sensitivity of 93%, but with no change in the specificity (79%). Another study presented at DDW was an international study conducted to develop up-to-date evidence-based consensus statements for the diagnosis of biliary strictures using pCLE.4 pCLE was more accurate than ERCP using brush cytology and/or forceps biopsy in determining the nature of strictures, according to established criteria. pCLE used during ERCP for the evaluation of biliary strictures can be considered a standard practice, complementary to conventional tissue sampling. pCLE can also be useful for excluding malignant biliary strictures. However, the accuracy of pCLE to evaluate biliary strictures may be decreased by previous plastic stents or by other factors. Therefore, high false positivity and low specificity rates remain problematic and increase the difficulty of interpreting borderline findings. There are no definitive results on corresponding histologic confirmation for individual findings on pCLE. In addition, the high cost of equipment and probes is an obstacle for standard clinical practices outside of the United States. The best method for preoperative biliary drainage for biliary obstruction in patients with resectable malignant distal common bile duct stricture has not been established. Endoscopic biliary drainage (EBD) using a plastic stent is routine in clinical practice, but plastic stents may cause high complication rates and perioperative morbidity. Routine preoperative EBD using plastic stents in patients with cancer of the pancreatic head that is potentially curable by surgery is associated with increased risk of complications including serious problems.5 The selfexpandable metallic stent (SEMS) was originally designed for endoscopic palliation of nonresectable malignant biliary strictures. The fully covered SEMSs (FCSEMS) are easy to
www.giejournal.org
Endoscopic retrograde cholangiopancreatography
remove and are associated with a long duration of patency because tissue hyperplasia does not occur and the metal wires do not become embedded in the biliary tree.6 The FCSEMS is an alternative to the plastic stent for preoperative EBD, and is expected to produce better results in patients with cancer of the pancreatic head who undergo subsequent surgical resection.7 González-Huix et al8 conducted an open-label RCT to compare pre- and post-surgical complications and procedure-related costs using FCSEMS (31 patients) vs. plastic stents (28 patients) in preoperative EBD for biliary obstruction caused by potentially resectable periampullary tumors in 63 patients. Pre-surgical complications in the FCSEMS group were significantly lower than those in the plastic stent group (3.8% vs. 37.5%, per protocol analysis). In addition, FCSEMS resulted in lower complication rates, shorter hospital stays, and fewer reinterventions without an increase in cost. FCSEMS did not cause difficulties during surgery. Surgical and post-surgical complications up to 1 month, and number of days in the intensive care unit were similar between the two stent groups. The authors concluded that FCSEMS is suitable for preoperative EBD. The patient population involved in this study was not sufficient to satisfy all conclusions; nevertheless, FCSEMS can be considered the first option for preoperative EBD of potentially resectable malignant distal common bile duct strictures. Benign biliary strictures can occur as a complication of biliary surgery or chronic pancreatitis. Endoscopic stenting is the mainstay of endoscopic management of benign biliary strictures. FCSEMS are the ideal stents to use for such strictures that are resistant to plastic stent placement.9 The role of FCSEMS for nonstrictured benign biliary diseases has not been established, but the short-term placement of FCSEMS can be effectively and safely applied not only for benign biliary strictures but also for nonstrictured benign biliary diseases, including leaks, perforations, and bleeding.10 However, frequent spontaneous stent migration is a major adverse event associated with FCSEMS.11 Continuous technical development for newly designed FCSEMS are needed before their routine use in these clinical setting.
ENDOBILIARY ABLATION THERAPY Surgical management of cholangiocarcinoma often requires radical excision. The incidence of unresectable cholangiocarcinoma is relatively high compared with malignancies of other organs. Therefore, palliation therapy including stenting is important for managing cholangiocarcinoma, especially the unresectable cases. However, the efficacy of conventional palliative treatment – including radiotherapy – has generally been unsatisfactory. Photodynamic therapy using a photosensitizing agent shows promise as a palliative treatment for cholangiocarcinoma.
Volume 80, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 389
Endoscopic retrograde cholangiopancreatography
Photodynamic therapy may have a positive effect on survival in unresectable cholangiocarcinoma,12 but results from further prospective RCTs are warranted. Radiofrequency ablation (RFA) is a new endobiliary ablation modality for the palliation of cholangiocarcinoma or occluded biliary SEMS.13 RFA appears to be effective for increasing stricture diameter according to initial human trials, but possible complications are a major concern. Kahaleh et al14 conducted a multicenter registry study comprising 62 patients to assess the safety and efficacy of RFA in cholangiocarcinoma. Placement of plastic stents or SEMS following wire-guided RFA was performed in 66 strictures with a mean stricture length of 14.3 mm. The mean stricture diameter after RFA increased from 2.05 mm to 4.9 mm. Adverse events occurred in seven patients (11%), including one case of cholecystitis and one of hemobilia. The other five patients experienced only post-procedural pain. These RFA preliminary results from a relatively large sample suggest that RFA can be applied safely with significant tumor ablation results. However, further RCTs should be conducted to validate the safety and effectiveness.
Moon et al
ERCP has been the gold standard for biliary tract lesions, but indirect radiologic imaging is an inherent limitation of ERCP. Peroral cholangioscopy (POC) permits direct visualization of the biliary tree for diagnostic procedures, and provides endoscopic guidance for therapeutic interventions. Three POC systems are currently available, including a mother–baby cholangioscopy system, and two single-operator cholangioscopy (SOC) systems utilizing the SpyGlass direct visualization system (Boston Scientific Corp., Natick, Massachusetts, United States) and direct POC using an ultraslim upper endoscope. SOC by SpyGlass is a clinically useful procedure for the diagnosis and therapy of bile duct lesions, including the management of bile duct stones that are resistant to conventional management.15 Kalaitzakis et al16 investigated the role of SOC using the SpyGlass system in 51 patients with sclerosing cholangitis, including four cases of IgG4-related cholangitis. A total of 54 SOC procedures were attempted for indeterminate biliary strictures in patients with sclerosing cholangitis. The control group included those patients with indeterminate biliary strictures without sclerosing cholangitis. The technical success rate of bile duct cholangioscope insertion was lower in the sclerosing cholangitis group (83% vs. 96%; P Z 0.05). The rate of adequate samples obtained from SOC-directed biopsies was 67% in the sclerosing cholangitis group. The sensitivity rate of SOC for diagnosis of malignant lesions was relatively low (50%) in the sclerosing cholangitis group, but almost similar to that of the control group (55%). Adverse events occurred frequently in the
sclerosing cholangitis group at a rate of 17.5%, with 11% experiencing cholangitis but not in its severe form. This important study suggests that SOC may be useful for the assessment of sclerosing cholangitis, but insertion of the cholangioscope can be challenging, and cholangitis can easily occur in patients with sclerosing cholangitis. Similar to the results of these studies, SOC has been shown to improve the management of bile duct lesions, especially in patients with nondilated bile ducts. However, unsatisfactory image quality with SOC using the current SpyGlass system makes it difficult to determine conclusive results. The development of cholangitis should be monitored after the procedure, especially in patients with sclerosing cholangitis. Direct POC using an ultraslim endoscope provides highquality, enhanced endoscopic imaging, a wide range of therapeutic options via a larger working channel, and lower costs compared with the SpyGlass and mother–baby systems. Specialized accessories or techniques for the success of direct POC are necessary to advance an ultraslim endoscope into the proximal biliary system from the second part of the duodenal lumen. An intraductal balloon through the working channel of the scope permits access, stability, and positioning of the ultraslim endoscope within the biliary system. Direct POC using an intraductal 5-Fr balloon catheter that can be anchored and fixed within a branch of the intrahepatic duct or proximal portion of a strictured segment has a high success rate.17 At DDW, Moon et al18 reported on a single-center experience of 394 direct POC sessions in 303 patients. The technical success rate was 96.7%, but 90.8% of these cases required assistive accessories. The rate of successful tissue sampling for histologic evaluation was 84.5%. The intended intraductal therapeutic interventions under direct POC were successfully performed in 85.0% of cases. The therapeutic procedures were conducted using a 2.0-mm-wide working channel. Surprisingly, direct POC-related complications were rare (1.8%), with no severe or mortalityrelated cases. These results suggest that direct POC can be conducted safely with a high technical success rate by an experienced biliary endoscopist. However, this POC modality has only been performed in a limited number of medical centers, because of the technically demanding nature of the procedure and limited assistive accessories. Anchoring of an intraductal balloon catheter is not always successful, especially in patients without a strictured biliary segment or impacted stones. Furthermore, direct POC is difficult to perform in patients with nondilated bile ducts because of the approximately 5-mm outer diameters of the scopes. The most common complication associated with POC is cholangitis. The administration of prophylactic antibiotics and suction of irrigated normal saline are mandatory to minimize the incidence of cholangitis. Carbon dioxide insufflation is strongly recommended rather than room air, to prevent fatal air embolism.
390 GASTROINTESTINAL ENDOSCOPY Volume 80, No. 3 : 2014
www.giejournal.org
PERORAL CHOLANGIOSCOPY
Moon et al
PERORAL PANCREATOSCOPY Peroral pancreatoscopy (POP) can be useful for evaluating pancreatic ductal lesions, similar to POC for biliary lesions, but its application is considerably limited. Among recent technical advances, a small-diameter videoscope capable of narrow-band imaging has been developed.19 The main indications for POP are the evaluation of suspected or definite intraductal papillary mucinous neoplasm (IPMN) and indeterminate pancreatic ductal stricture. Interventional procedures, including tissue sampling or shockwave lithotripsy of pancreatic duct stones, are possible on direct visualization. Hajj et al20 performed a single-center trial in the United States to evaluate the safety and efficacy of POP in patients with suspected main pancreatic duct neoplasia. A total of 102 POP procedures were performed in 78 patients. The indications for POP were indeterminate main pancreatic duct strictures and/or dilations in patients with chronic pancreatitis (n Z 45), main pancreatic duct dilations in patients without chronic pancreatitis (n Z 8), suspected IPMNs (n Z 14), and known IPMNs (n Z 11). Technical success was achieved in 98% of patients (77/78). POPdirected biopsy using a pancreatoscope was performed in 21 patients. The sensitivity of POP-directed and POPassisted tissue sampling was 81%. Complications arose in 14 patients (13.7% of procedures), four of whom had pancreatitis. This study concluded that POP can be performed safely by endoscopy experts with high success rates in nearly all patients with dilated and suspected main pancreatic duct neoplasia. However, a higher incidence of PEP in patients who underwent POP compared with POC is apparent, even after placement of a prophylactic pancreatic duct stent after ERCP.21 Therefore, POP can be applied to limited pancreatic lesions in dilated main pancreatic ducts, but there is a risk of post-procedural pancreatitis. Further technical development is warranted before routine clinical application in pancreatic diseases can be recommended. REFERENCES 1. Kaplan JH, Zabolotsky AH, Kowalski TE, et al. A trial of rectal indomethacin to prevent post-ERCP pancreatitis in patients with sphincter of Oddi dysfunction type 3 [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB314. 2. Chahal P, Tarnasky PR, Petersen BT, et al. Short 5Fr vs long 3Fr pancreatic stents in patients at risk for post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2009;7:834-9. 3. Slivka A, Gan SI, Giovannini M, et al. Accuracy of optical biopsy using probe based confocal laser endomicroscopy (pCLE) in patients with indeterminate biliary strictures: interim results with modified criteria of a large multicentric study [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB371. 4. Carr-Locke DL, Arsenescu R, Bertani H, et al. The role of confocal laser endomicroscopy in the management of patients with biliary strictures: a consensus report based on clinical evidence. Gastroenterology 2014;146(5 suppl 1) S-387-8.
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Endoscopic retrograde cholangiopancreatography 5. van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med 2010;362:129-37. 6. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004;53:729-34. 7. Kahaleh M, Brock A, Conaway MR, et al. Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis. Endoscopy 2007;39:319-24. 8. González-Huix F, Figa M, Alburquerque M, et al. Metallic vs. plastic stent in the preoperative treatment for biliary obstruction of resectable periampullary tumours: a randomized controlled trial [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB401. 9. Kaffes AJ, Liu K. Fully covered self-expandable metal stents for treatment of benign biliary strictures. Gastrointest Endosc 2013;78:13-21. 10. Irani S, Baron TH, Law R, et al. Endoscopic treatment of non-stricture related benign biliary diseases using covered self-expandable metal stents (CSEMS) [abstract]. Gastrointest Endosc 2014;79(suppl 5): AB356-7. 11. Park do H, Lee SS, Lee TH, et al. Anchoring flap versus flared end, fully covered self-expandable metal stents to prevent migration in patients with benign biliary strictures: a multicenter, prospective, comparative pilot study (with videos). Gastrointest Endosc 2011;73:64-70. 12. Ortner ME, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 2003;125:1355-63. 13. Monga A, Gupta R, Ramchandani M, et al. Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative treatment modality (with videos). Gastrointest Endosc 2011;74:935-7. 14. Kahaleh M, Sharaiha RZ, Sethi A, et al. Radiofrequency ablation for palliation of malignant biliary strictures: an American collaborative experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB339. 15. Chen YK, Parsi MA, Binmoeller KF, et al. Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos). Gastrointest Endosc 2011;74:805-14. 16. Kalaitzakis E, Sturgess R, Kaltsidis H, et al. Diagnostic utility of single-user peroral cholangioscopy for indeterminate biliary strictures in sclerosing cholangitis [abstract]. Gastrointest Endosc 2014;79 (suppl 5):AB347. 17. Moon JH, Ko BM, Choi HJ, et al. Intraductal balloon-guided direct peroral cholangioscopy with an ultraslim upper endoscope (with videos). Gastrointest Endosc 2009;70:297-302. 18. Moon JH, Choi HJ, Ko BM, et al. Direct peroral cholangioscopy using an ultra-slim upper endoscope: a single center experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB130. 19. Itoi T, Sofuni A, Itokawa F, et al. Initial experience of peroral pancreatoscopy combined with narrow-band imaging in the diagnosis of intraductal papillary mucinous neoplasms of the pancreas (with videos). Gastrointest Endosc 2007;66:793-7. 20. Hajj IE, Brauer BC, Fukami N, et al. Role of peroral pancreatoscopy (POP) in the evaluation of suspected main pancreatic duct (MPD) neoplasia: a 13-year U.S. single center experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB130. 21. Kistler CA, Francis G, Kowalski TE, et al. Rates of adverse events in patients undergoing single-operator peroral cholangioscopy and pancreatoscopy [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB315.
Received July 1, 2014. Accepted July 1, 2014. Current affiliations: Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon/Seoul, Korea. Reprint requests: Jong Ho Moon, MD, PhD, Digestive Disease Center, Soon Chun Hyang University School of Medicine, Bucheon Hospital, 1174 JungDong, Wonmi-Ku, Bucheon 420-767, Korea.
Volume 80, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 391
Endoscopic retrograde cholangiopancreatography Jong Ho Moon, MD, PhD, Hyun Jong Choi, Yun Nah Lee Bucheon, Seoul, Korea
New technological developments in endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment have been slow to progress. However, several informative study results were presented during the 2014 Digestive Disease Week (DDW; 3–6 May; Chicago, Illinois, USA) in specific ERCP areas, such as prevention of post-ERCP pancreatitis using nonsteroidal antiinflammatory drugs and pancreatic duct stenting. Novel and interesting study results regarding preoperative stent selection for periampullary tumors, metal stents for hilar stricture or for prevention of duodenal reflux, and intraductal biliary tumor ablation using photodynamic therapy or radiofrequency ablation were discussed. Study results presented at the meeting regarding single-operator cholangioscopy using the SpyGlass system or direct peroral cholangioscopy have indicated the possibility of future development. Results using peroral pancreatoscopy and confocal laser endomicroscopy for biliary lesions, including strictures, were also presented.
POST-ERCP PANCREATITIS ERCP is used as a standard endoscopic procedure for the management of biliopancreatic lesions, even though it is an invasive procedure that may provoke adverse events. Therefore, trials aimed at minimizing complications should be conducted continually to improve safety. Post-ERCP pancreatitis (PEP) is still the most problematic adverse event associated with ERCP. However, pharmacologic Abbreviations: DDW, Digestive Disease Week; EBD, endoscopic biliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; FCSEMS, fully covered SEMS; IPMN, intraductal papillary mucinous neoplasm; pCLE, probe-based confocal laser endomicroscopy; PEP, postERCP pancreatitis; POC, peroral cholangioscopy; POP, peroral pancreatoscopy; RCT, randomized, controlled trial; RFA, radiofrequency ablation; SEMS, self-expandable metallic stent; SOC, single-operator cholangioscopy. DISCLOSURE: All authors disclosed no financial relationships relevant to this article. This report is published simultaneously in the journals Gastrointestinal Endoscopy and Endoscopy. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy and ª Georg Thieme Verlag KG 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.07.004
388 GASTROINTESTINAL ENDOSCOPY Volume 80, No. 3 : 2014
prevention using nonsteroidal anti-inflammatory drugs and interventional prevention using pancreatic duct stenting have revealed significant improvements in the prevention of PEP. Administration of nonsteroidal anti-inflammatory drugs combined with prophylactic pancreatic duct stent placement may be ideal for preventing PEP. Kaplan et al.1 presented retrospective results of prophylactic rectal indomethacin combined with pancreatic duct stenting in 57 patients; these patients were compared with 285 patients who underwent pancreatic duct stenting alone, in order to determine the effects of each treatment on reducing the incidence and severity of PEP in patients undergoing manometry for suspected sphincter of Oddi dysfunction type 3. A single-dose indomethacin (100 mg) suppository was administered after ERCP. There were no statistically significant differences between the stent plus indomethacin group and the stent only group in terms of the incidence of PEP (18% vs. 23%), moderate-to-severe pancreatitis (9% vs. 7%), and the median duration of hospital stay (4 vs. 6 days). These results suggest that prophylactic rectally administered indomethacin combined with pancreatic duct stenting did not affect the incidence or severity of PEP when compared with pancreatic duct stenting alone in highrisk patients undergoing manometry, but further studies are warranted. In addition, the indomethacin dose and administration time necessary for the most effective prevention of PEP should be documented. Pancreatic duct stenting is an important method of preventing PEP, but there is still controversy regarding the ideal plastic stent, including its diameter, to be used for this purpose. A prospective multicenter, randomized, controlled trial (RCT) was conducted in patients at high risk of PEP, to investigate the rates of PEP and spontaneous distal migration when using unflanged, long-length, 3-Fr pancreatic duct stents compared with short-length, 5-Fr pancreatic duct stents.2 The 5-Fr stent was more efficacious than the 3-Fr stent in terms of spontaneous dislodgement rate and prevention of PEP among high-risk patients. These results suggest that the use of conventional 5-Fr pancreatic duct stents using a conventional 0.035-inch guidewire is a reasonable method for preventing PEP. However, continued stent development is needed to find more ideal stents for PEP prevention. In addition, the ideal stent length and rate of spontaneous dislodgement need to be determined. www.giejournal.org
Moon et al
BILIARY STRICTURES AND STENTS Histopathologic confirmation is critical for the management of biliary stricture, but acquisition of adequate endoscopic tissue for a definite diagnosis is not always successful. Probe-based confocal laser endomicroscopy (pCLE) is a new endoscopic diagnostic modality that allows real-time optical biopsy for immediate in vivo histology after positioning the probe in the area of interest. The probe can be delivered via a catheter during ERCP or via direct visualization using a cholangioscope. Several ongoing trials are investigating the diagnosis of biliary stricture using pCLE in order to overcome the issues surrounding current endoscopic tissue acquisition methods. Slivka et al3 reported interim study results from an international multicenter trial of the impact of pCLE on patients with indeterminate biliary strictures, according to a refined classification. The addition of pCLE increased the sensitivity to 89% compared with 82% using clinical history and ERCP alone. The specificity also increased from 71% to 79%. Tissue sampling combined with pCLE allowed an even greater sensitivity of 93%, but with no change in the specificity (79%). Another study presented at DDW was an international study conducted to develop up-to-date evidence-based consensus statements for the diagnosis of biliary strictures using pCLE.4 pCLE was more accurate than ERCP using brush cytology and/or forceps biopsy in determining the nature of strictures, according to established criteria. pCLE used during ERCP for the evaluation of biliary strictures can be considered a standard practice, complementary to conventional tissue sampling. pCLE can also be useful for excluding malignant biliary strictures. However, the accuracy of pCLE to evaluate biliary strictures may be decreased by previous plastic stents or by other factors. Therefore, high false positivity and low specificity rates remain problematic and increase the difficulty of interpreting borderline findings. There are no definitive results on corresponding histologic confirmation for individual findings on pCLE. In addition, the high cost of equipment and probes is an obstacle for standard clinical practices outside of the United States. The best method for preoperative biliary drainage for biliary obstruction in patients with resectable malignant distal common bile duct stricture has not been established. Endoscopic biliary drainage (EBD) using a plastic stent is routine in clinical practice, but plastic stents may cause high complication rates and perioperative morbidity. Routine preoperative EBD using plastic stents in patients with cancer of the pancreatic head that is potentially curable by surgery is associated with increased risk of complications including serious problems.5 The selfexpandable metallic stent (SEMS) was originally designed for endoscopic palliation of nonresectable malignant biliary strictures. The fully covered SEMSs (FCSEMS) are easy to
www.giejournal.org
Endoscopic retrograde cholangiopancreatography
remove and are associated with a long duration of patency because tissue hyperplasia does not occur and the metal wires do not become embedded in the biliary tree.6 The FCSEMS is an alternative to the plastic stent for preoperative EBD, and is expected to produce better results in patients with cancer of the pancreatic head who undergo subsequent surgical resection.7 González-Huix et al8 conducted an open-label RCT to compare pre- and post-surgical complications and procedure-related costs using FCSEMS (31 patients) vs. plastic stents (28 patients) in preoperative EBD for biliary obstruction caused by potentially resectable periampullary tumors in 63 patients. Pre-surgical complications in the FCSEMS group were significantly lower than those in the plastic stent group (3.8% vs. 37.5%, per protocol analysis). In addition, FCSEMS resulted in lower complication rates, shorter hospital stays, and fewer reinterventions without an increase in cost. FCSEMS did not cause difficulties during surgery. Surgical and post-surgical complications up to 1 month, and number of days in the intensive care unit were similar between the two stent groups. The authors concluded that FCSEMS is suitable for preoperative EBD. The patient population involved in this study was not sufficient to satisfy all conclusions; nevertheless, FCSEMS can be considered the first option for preoperative EBD of potentially resectable malignant distal common bile duct strictures. Benign biliary strictures can occur as a complication of biliary surgery or chronic pancreatitis. Endoscopic stenting is the mainstay of endoscopic management of benign biliary strictures. FCSEMS are the ideal stents to use for such strictures that are resistant to plastic stent placement.9 The role of FCSEMS for nonstrictured benign biliary diseases has not been established, but the short-term placement of FCSEMS can be effectively and safely applied not only for benign biliary strictures but also for nonstrictured benign biliary diseases, including leaks, perforations, and bleeding.10 However, frequent spontaneous stent migration is a major adverse event associated with FCSEMS.11 Continuous technical development for newly designed FCSEMS are needed before their routine use in these clinical setting.
ENDOBILIARY ABLATION THERAPY Surgical management of cholangiocarcinoma often requires radical excision. The incidence of unresectable cholangiocarcinoma is relatively high compared with malignancies of other organs. Therefore, palliation therapy including stenting is important for managing cholangiocarcinoma, especially the unresectable cases. However, the efficacy of conventional palliative treatment – including radiotherapy – has generally been unsatisfactory. Photodynamic therapy using a photosensitizing agent shows promise as a palliative treatment for cholangiocarcinoma.
Volume 80, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 389
Endoscopic retrograde cholangiopancreatography
Photodynamic therapy may have a positive effect on survival in unresectable cholangiocarcinoma,12 but results from further prospective RCTs are warranted. Radiofrequency ablation (RFA) is a new endobiliary ablation modality for the palliation of cholangiocarcinoma or occluded biliary SEMS.13 RFA appears to be effective for increasing stricture diameter according to initial human trials, but possible complications are a major concern. Kahaleh et al14 conducted a multicenter registry study comprising 62 patients to assess the safety and efficacy of RFA in cholangiocarcinoma. Placement of plastic stents or SEMS following wire-guided RFA was performed in 66 strictures with a mean stricture length of 14.3 mm. The mean stricture diameter after RFA increased from 2.05 mm to 4.9 mm. Adverse events occurred in seven patients (11%), including one case of cholecystitis and one of hemobilia. The other five patients experienced only post-procedural pain. These RFA preliminary results from a relatively large sample suggest that RFA can be applied safely with significant tumor ablation results. However, further RCTs should be conducted to validate the safety and effectiveness.
Moon et al
ERCP has been the gold standard for biliary tract lesions, but indirect radiologic imaging is an inherent limitation of ERCP. Peroral cholangioscopy (POC) permits direct visualization of the biliary tree for diagnostic procedures, and provides endoscopic guidance for therapeutic interventions. Three POC systems are currently available, including a mother–baby cholangioscopy system, and two single-operator cholangioscopy (SOC) systems utilizing the SpyGlass direct visualization system (Boston Scientific Corp., Natick, Massachusetts, United States) and direct POC using an ultraslim upper endoscope. SOC by SpyGlass is a clinically useful procedure for the diagnosis and therapy of bile duct lesions, including the management of bile duct stones that are resistant to conventional management.15 Kalaitzakis et al16 investigated the role of SOC using the SpyGlass system in 51 patients with sclerosing cholangitis, including four cases of IgG4-related cholangitis. A total of 54 SOC procedures were attempted for indeterminate biliary strictures in patients with sclerosing cholangitis. The control group included those patients with indeterminate biliary strictures without sclerosing cholangitis. The technical success rate of bile duct cholangioscope insertion was lower in the sclerosing cholangitis group (83% vs. 96%; P Z 0.05). The rate of adequate samples obtained from SOC-directed biopsies was 67% in the sclerosing cholangitis group. The sensitivity rate of SOC for diagnosis of malignant lesions was relatively low (50%) in the sclerosing cholangitis group, but almost similar to that of the control group (55%). Adverse events occurred frequently in the
sclerosing cholangitis group at a rate of 17.5%, with 11% experiencing cholangitis but not in its severe form. This important study suggests that SOC may be useful for the assessment of sclerosing cholangitis, but insertion of the cholangioscope can be challenging, and cholangitis can easily occur in patients with sclerosing cholangitis. Similar to the results of these studies, SOC has been shown to improve the management of bile duct lesions, especially in patients with nondilated bile ducts. However, unsatisfactory image quality with SOC using the current SpyGlass system makes it difficult to determine conclusive results. The development of cholangitis should be monitored after the procedure, especially in patients with sclerosing cholangitis. Direct POC using an ultraslim endoscope provides highquality, enhanced endoscopic imaging, a wide range of therapeutic options via a larger working channel, and lower costs compared with the SpyGlass and mother–baby systems. Specialized accessories or techniques for the success of direct POC are necessary to advance an ultraslim endoscope into the proximal biliary system from the second part of the duodenal lumen. An intraductal balloon through the working channel of the scope permits access, stability, and positioning of the ultraslim endoscope within the biliary system. Direct POC using an intraductal 5-Fr balloon catheter that can be anchored and fixed within a branch of the intrahepatic duct or proximal portion of a strictured segment has a high success rate.17 At DDW, Moon et al18 reported on a single-center experience of 394 direct POC sessions in 303 patients. The technical success rate was 96.7%, but 90.8% of these cases required assistive accessories. The rate of successful tissue sampling for histologic evaluation was 84.5%. The intended intraductal therapeutic interventions under direct POC were successfully performed in 85.0% of cases. The therapeutic procedures were conducted using a 2.0-mm-wide working channel. Surprisingly, direct POC-related complications were rare (1.8%), with no severe or mortalityrelated cases. These results suggest that direct POC can be conducted safely with a high technical success rate by an experienced biliary endoscopist. However, this POC modality has only been performed in a limited number of medical centers, because of the technically demanding nature of the procedure and limited assistive accessories. Anchoring of an intraductal balloon catheter is not always successful, especially in patients without a strictured biliary segment or impacted stones. Furthermore, direct POC is difficult to perform in patients with nondilated bile ducts because of the approximately 5-mm outer diameters of the scopes. The most common complication associated with POC is cholangitis. The administration of prophylactic antibiotics and suction of irrigated normal saline are mandatory to minimize the incidence of cholangitis. Carbon dioxide insufflation is strongly recommended rather than room air, to prevent fatal air embolism.
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PERORAL CHOLANGIOSCOPY
Moon et al
PERORAL PANCREATOSCOPY Peroral pancreatoscopy (POP) can be useful for evaluating pancreatic ductal lesions, similar to POC for biliary lesions, but its application is considerably limited. Among recent technical advances, a small-diameter videoscope capable of narrow-band imaging has been developed.19 The main indications for POP are the evaluation of suspected or definite intraductal papillary mucinous neoplasm (IPMN) and indeterminate pancreatic ductal stricture. Interventional procedures, including tissue sampling or shockwave lithotripsy of pancreatic duct stones, are possible on direct visualization. Hajj et al20 performed a single-center trial in the United States to evaluate the safety and efficacy of POP in patients with suspected main pancreatic duct neoplasia. A total of 102 POP procedures were performed in 78 patients. The indications for POP were indeterminate main pancreatic duct strictures and/or dilations in patients with chronic pancreatitis (n Z 45), main pancreatic duct dilations in patients without chronic pancreatitis (n Z 8), suspected IPMNs (n Z 14), and known IPMNs (n Z 11). Technical success was achieved in 98% of patients (77/78). POPdirected biopsy using a pancreatoscope was performed in 21 patients. The sensitivity of POP-directed and POPassisted tissue sampling was 81%. Complications arose in 14 patients (13.7% of procedures), four of whom had pancreatitis. This study concluded that POP can be performed safely by endoscopy experts with high success rates in nearly all patients with dilated and suspected main pancreatic duct neoplasia. However, a higher incidence of PEP in patients who underwent POP compared with POC is apparent, even after placement of a prophylactic pancreatic duct stent after ERCP.21 Therefore, POP can be applied to limited pancreatic lesions in dilated main pancreatic ducts, but there is a risk of post-procedural pancreatitis. Further technical development is warranted before routine clinical application in pancreatic diseases can be recommended. REFERENCES 1. Kaplan JH, Zabolotsky AH, Kowalski TE, et al. A trial of rectal indomethacin to prevent post-ERCP pancreatitis in patients with sphincter of Oddi dysfunction type 3 [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB314. 2. Chahal P, Tarnasky PR, Petersen BT, et al. Short 5Fr vs long 3Fr pancreatic stents in patients at risk for post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2009;7:834-9. 3. Slivka A, Gan SI, Giovannini M, et al. Accuracy of optical biopsy using probe based confocal laser endomicroscopy (pCLE) in patients with indeterminate biliary strictures: interim results with modified criteria of a large multicentric study [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB371. 4. Carr-Locke DL, Arsenescu R, Bertani H, et al. The role of confocal laser endomicroscopy in the management of patients with biliary strictures: a consensus report based on clinical evidence. Gastroenterology 2014;146(5 suppl 1) S-387-8.
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Endoscopic retrograde cholangiopancreatography 5. van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med 2010;362:129-37. 6. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004;53:729-34. 7. Kahaleh M, Brock A, Conaway MR, et al. Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis. Endoscopy 2007;39:319-24. 8. González-Huix F, Figa M, Alburquerque M, et al. Metallic vs. plastic stent in the preoperative treatment for biliary obstruction of resectable periampullary tumours: a randomized controlled trial [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB401. 9. Kaffes AJ, Liu K. Fully covered self-expandable metal stents for treatment of benign biliary strictures. Gastrointest Endosc 2013;78:13-21. 10. Irani S, Baron TH, Law R, et al. Endoscopic treatment of non-stricture related benign biliary diseases using covered self-expandable metal stents (CSEMS) [abstract]. Gastrointest Endosc 2014;79(suppl 5): AB356-7. 11. Park do H, Lee SS, Lee TH, et al. Anchoring flap versus flared end, fully covered self-expandable metal stents to prevent migration in patients with benign biliary strictures: a multicenter, prospective, comparative pilot study (with videos). Gastrointest Endosc 2011;73:64-70. 12. Ortner ME, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 2003;125:1355-63. 13. Monga A, Gupta R, Ramchandani M, et al. Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative treatment modality (with videos). Gastrointest Endosc 2011;74:935-7. 14. Kahaleh M, Sharaiha RZ, Sethi A, et al. Radiofrequency ablation for palliation of malignant biliary strictures: an American collaborative experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB339. 15. Chen YK, Parsi MA, Binmoeller KF, et al. Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos). Gastrointest Endosc 2011;74:805-14. 16. Kalaitzakis E, Sturgess R, Kaltsidis H, et al. Diagnostic utility of single-user peroral cholangioscopy for indeterminate biliary strictures in sclerosing cholangitis [abstract]. Gastrointest Endosc 2014;79 (suppl 5):AB347. 17. Moon JH, Ko BM, Choi HJ, et al. Intraductal balloon-guided direct peroral cholangioscopy with an ultraslim upper endoscope (with videos). Gastrointest Endosc 2009;70:297-302. 18. Moon JH, Choi HJ, Ko BM, et al. Direct peroral cholangioscopy using an ultra-slim upper endoscope: a single center experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB130. 19. Itoi T, Sofuni A, Itokawa F, et al. Initial experience of peroral pancreatoscopy combined with narrow-band imaging in the diagnosis of intraductal papillary mucinous neoplasms of the pancreas (with videos). Gastrointest Endosc 2007;66:793-7. 20. Hajj IE, Brauer BC, Fukami N, et al. Role of peroral pancreatoscopy (POP) in the evaluation of suspected main pancreatic duct (MPD) neoplasia: a 13-year U.S. single center experience [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB130. 21. Kistler CA, Francis G, Kowalski TE, et al. Rates of adverse events in patients undergoing single-operator peroral cholangioscopy and pancreatoscopy [abstract]. Gastrointest Endosc 2014;79(suppl 5):AB315.
Received July 1, 2014. Accepted July 1, 2014. Current affiliations: Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon/Seoul, Korea. Reprint requests: Jong Ho Moon, MD, PhD, Digestive Disease Center, Soon Chun Hyang University School of Medicine, Bucheon Hospital, 1174 JungDong, Wonmi-Ku, Bucheon 420-767, Korea.
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