ERCP with Digital Pancreatoscopy-Guided Stone Fragmentation: Breaking Up Is Easy to Do

When presented with a patient complaining of chronic abdominal pain, gastroenterologists are often relieved to uncover an identifiable and treatable cause due to the often perplexing nature of this complaint. As Atul Gawande in Being Mortal wrote, “our job in medicine…is to enable well-being” [1]. In the setting of chronic calcific pancreatitis and associated main pancreatic duct stones and strictures, intraductal hypertension likely contributes to the pathogenesis of pain [2]. Though limited randomized controlled trials suggest that patients with obstructive chronic pancreatitis, specifically with head obstruction and proximal dilatation of the duct, may benefit more from decompressive surgery than from endoscopic therapy, these studies do not address treating pancreatic duct stones nor those with obstructive disease distal to the head [3]. Furthermore, the endoscopic therapy study arms were not sufficiently “intensive” enough to resolve PD stones and distal strictures. Lastly, patients almost universally prefer less invasive therapies to manage their disease condition, especially with the foreknowledge that other factors such as the neuropathic pain of chronic pancreatitis may eventually emerge [4].

The advent of intraductal endoscopy has permitted the targeting of large obstructing biliary and pancreatic duct stones for lithotripsy followed by the removal of fragments during the same endoscopic session. Yet, technical difficulty and limited expertise has contributed to only select centers offering pancreatoscopy for treating stones. Improvements in catheter-based technology with digital single-operator cholangiopancreatoscopy (DSOC) that include optical resolution and tip articulation used in pancreatoscopy have increased overall enthusiasm for this approach [5].

In this issue of Digestive Diseases and Sciences, Ogura et al. [6] present a retrospective single-center study using DSOC-guided electrohydraulic lithotripsy (EHL) for the management of main pancreatic duct stones in a Japanese population with chronic calcific pancreatitis. Though traditional methods have included extracorporeal shock-wave lithotripsy (ESWL) for fragmentation of stones, ESWL alone cannot treat strictures that may prevent stone fragment removal and lead to stone recurrence and pain; it also has decreased efficacy for very dense, hard stones (attenuation > 900 Hounsfield Units [HU]) and in patients with high body mass indices [7]. On the other hand, large, impacted stones can limit deep guidewire access during endoscopic retrograde cholangiopancreatography (ERCP) preventing stone removal. The most recent guidelines promulgated by the American Society for Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy recommend intraductal therapies such as EHL or laser lithotripsy (LL) via per-oral pancreatoscopy as a second-line option after failure of ESWL or conventional ERCP, noting the dearth of evidence to support these techniques [8, 9]. Indeed, relatively small retrospective case series form the bulk of evidence describing the use of intraductal therapy, which complicate the determination of its specific contribution to the algorithm used for the treatment of pancreatic duct stones and whether it can be a successful adjunctive therapy to conventional ERCP or ESWL.

This small and select study population provides some evidence supporting the efficacy of DSOC and EHL in fragmenting and removing pancreatic duct stones. Of the 21 included patients, DSOC successfully enabled EHL in 18 (85.7%) patients, with complete stone clearance achieved in all 18 patients who received EHL, in line with previous larger studies examining the effectiveness of per-oral pancreatoscopy-guided lithotripsy using either EHL or LL, which demonstrated technical success rates of 79–100% [10, 11]. In comparison, a meta-analysis of studies examining ESWL for pancreatic duct stones found a pooled ductal clearance rate of only 70.7%, whereas conventional ERCP techniques carry a ductal clearance rate near 50% [12, 13]. Moreover, the 85.7% stone clearance rate in this study is the highest reported among case series for EHL alone, which is the authors’ preferred first-line intraductal therapy for refractory stones, reserving LL for EHL failures. A mean of 1.29 ERCP sessions was required for success, which was slightly lower than the two sessions of ESWL required for stone clearance with or without adjunctive ERCP in the only randomized controlled trial comparing conventional ERCP with ESWL [14]. Interestingly, in the present study, the authors utilized dual operators with a “mother-daughter” approach, a more resource-intensive method. The three failures in this study were primarily due to tight pancreatic duct strictures, which prevented DSOC, illustrating the main limitation of per-oral pancreatoscopy: The inability to cannulate the duct using the pancreatoscopy platform, whether due to a tight stricture or a large obstructing stone at the head of the pancreas, may preclude intraductal lithotripsy. Nevertheless, in our experience, even if only the tip of the pancreatoscope can bridge the pancreatic orifice to target an obstructing stone, intraductal lithotripsy can be performed. DSOC-guided laser therapy may also provide a platform to dissect obstructing strictures immediately distal to the stones, improving tip articulation to facilitate lithotripsy [15]. In either event, this limitation presents the situation in which ESWL may be adjunctive to DSOC or conventional ERCP where stones can be fragmented and strictures can be dilated/stented prior to intraductal lithotripsy.

Although none of the patients in this study received ESWL, it is unclear why the patients who had failed DSOC went on to surgery and EUS-guided ductal decompression without an attempt at ESWL. We generally will stent distal strictures, when feasible, and refer for ESWL to fragment obstructing stones if the index ERCP suggests that DSOC will not be feasible. The study does support DSOC as a potential first-line treatment option for large main duct stones (median stone diameter of 12 mm in this study). Furthermore, while the study notes that all symptoms including abdominal pain resolved after stone removal, the duration of symptom improvement as well as other important patient-centered outcomes such as quality-of-life and patient-reported pain levels was not collected. Lastly, while not specifically mentioned, the follow-up period could not have exceeded 1–2 years given the relatively recent introduction of the DSOC. As chronic pancreatitis is a long-term disease marked with acute exacerbations and numerous complications, longer follow-up is needed to ascertain the clinical effectiveness of this procedure.

The safety profile of DSOC and EHL remains a key aspect in supporting its use as a treatment modality for pancreatic duct stones. In this study, the only adverse event was a single, mild episode of post-ERCP pancreatitis. Similarly, previous studies have shown an adverse event rate ranging from 0 to 13.5%, primarily consisting of abdominal pain flares that may reflect institutional practice in the use of “observation” or “extended recovery” [16] For comparison, the pooled adverse event rate of ESWL ranges from 5.8 to 6.7% [12].

In summary, Ogura et al. provide important data regarding DSOC and EHL for the management of large pancreatic duct stones in the main pancreatic duct. While its limitations include its small, homogeneous, and retrospectively obtained study population, it demonstrates a high technical success rate in a difficult patient population. With growing evidence demonstrating the safety and efficacy of per-oral pancreatos-copy for the management of pancreatic duct stones, several important questions do remain before this technique can be more widely adopted. Given that ESWL remains a first-line therapy in Europe and Asia, a randomized controlled trial is urgently needed to compare ESWL with per-oral pancreatoscopy-guided lithotripsy. Future trials should evaluate the effect of lithotripsy on important patient-centered outcomes such as quality-of-life and validated pain scores. Lastly, the technical expertise required to perform pancreatoscopy cannot be understated and remains an obstacle to its widespread use. These are complex procedures, and in the authors’ opinion, comfort and expertise with therapeutic pancreatic duct stenting and cholangioscopy are prerequisites to launching a practice in pancreatoscopy since data regarding learning curves are lacking. Intraductal endoscopy is an exciting field; the utilization of pancreatoscopy to detect neoplasia and “shock” stones is in its infancy.

Take Home Points.

• Digital single-operator cholangiopancreatoscopy for the treatment of main pancreatic duct stones using electrohydraulic lithotripsy is effective with a low adverse event rate

• Technical expertise in pancreatic endotherapy is a prerequisite to initiating pancreatoscopy-guided lithotripsy.

• Future studies will need to compare pancreatoscopy to ESWL in facilitating the clearance of main pancreatic duct stones and assess patient-centered outcomes of quality-of-life, validated pain scores, and longer-term follow-up in this complex chronic condition.