It has been estimated that 44,000 new cases of pancreatic cancer will be diagnosed and 37,000 deaths will occur in 2012.1 The vast majority of these patients are unresectable and consequently suffer from substantial morbidity, including obstruction of the distal bile duct. In patients with pancreatic head cancer, as well as those with other cancers that result in biliary obstruction (eg, cholangiocarcinoma and ampullary adenocarcinoma), endoscopic treatment is often successful in alleviating symptoms, reducing the risk of cholangitis, and improving biliary drainage so that hepatically metabolized chemotherapeutic agents can be used safely.2 Furthermore, over the past decade, there has been a preponderance of data suggesting that endoscopic placement of a self-expandable metal stent (SEMS) in nonresectable patients or in those whose surgical status is uncertain is cost-effective.3,4
Unfortunately, in a certain percentage of patients with malignant biliary obstruction, conventional endoscopic placement of an SEMS is not feasible because of the inability to perform, or the failure of, endoscopic retrograde cholangiography (ERC). Usually this occurs when the ampulla is inaccessible because of duodenal obstruction from an invading tumor, or when cannulation of the major papilla is unsuccessful. When these situations are encountered, conventional options include either surgical biliary bypass or percutaneous transhepatic biliary drainage (PTBD). During PTBD, the goal of the interventional radiologist is to either percutaneously place a SEMS or, if not feasible, place an external drainage catheter, with the hopes of internalizing it in the future. PTBD, however, is a more invasive procedure than endoscopy and carries with it a complication rate of up to 30%.5
Over the past few years, another option has been increasingly reported in small case series: endoscopic ultrasound (EUS)-guided access to the bile duct. Intuitively, to endosonographers, this makes sense, as the extrahepatic bile duct is visualized in exquisite detail with EUS and is only a short distance away from the duodenal wall. Furthermore, the therapeutic, linear-array echoendoscope has an oblique-viewing lens, a large working channel, and an elevator to help direct devices, much like a duodenoscope used for ERC. In this issue of the Journal of Clinical Gastroenterology, Artifon and colleagues present the first prospective, randomized study comparing EUS-choledochoduodenostomy (EUS-CD; placing an SEMS through the duodenal wall into the bile duct) with conventional PTBD.6 The authors are to be commended on 2 fronts: first, for comparing EUS-CD directly with PTBD, which as mentioned above is the most common “rescue” procedure for failed ERC, and, second, for using a technique that is quite straightforward and familiar to well-trained therapeutic endoscopists. In fact, the steps involved are nearly identical to those of EUS-guided pseudocyst drainage, including use of the same devices.
Artifon and colleagues randomized 25 unresectable patients with failed ERC or EUS-guided transpapillary rendezvous (of a total of 149 patients referred) to either EUS-CD or PTBD. Preprocedural characteristics of the 2 groups, including the size of their bile ducts and degree of hyperbilirubinemia, were similar. The technical success in both groups was 100% and outcomes were not statistically different between them, including the degree of improvement in serum bilirubin levels, length of hospital stay, quality of life, and low rate of complications. The overall complication rate in the EUS-CD group was 15%, and both cases were mild. There was only 1 bile leak. Although there was a trend toward lower costs of EUS-CD compared with PTBD, this was not statistically significant. Mean follow-up was fewer than 80 days, although the authors pointed out that this was largely because 76% of the patients were not alive at 3 months. The study reported no incidents of stent migration, presumably because of the exclusive use of partially covered SEMS, which likely has a lower risk of migration compared with fully covered SEMS.
Although the authors are to be commended on presenting the first randomized study comparing an “experimental” technique with an established technique for biliary drainage, the study’s biggest weakness is that the numbers in each arm are small, and therefore the study is likely not adequately powered. In addition, the patient population appears to be highly selected and may represent more advanced disease than the average therapeutic endoscopist sees on a daily basis—for example, patients with very high bilirubin levels, nonresectable patients (borderline resectable patients were not included), and a high number of patients in whom standard ERC had failed (>25%). Nevertheless, the authors recognize that this is a pilot study and provide thought-provoking data suggesting that EUS-CD, in expert hands, may be a reasonable alternative to PTBD.
Hence, is EUS-CD ready for prime time? I think it may be close. It was first reported >10 years ago by Giovannini and colleagues, and since then several reports have demonstrated its safety and efficacy.7–20 In addition to being less invasive compared with its nonendoscopic alternatives,17,18 it certainly has many other benefits including use of familiar techniques and devices, the ability to be performed at the same session when ERC fails, immediate internal drainage, and advantages over PTBD, including lack of pain at the percuatenous site and avoidance of the inconvenience of an external drainage bag when an internal stent cannot be placed. Despite the enthusiasm, however, there are still many unanswered questions. First, and most obviously, will the positive data presented by Artifon and colleagues hold up in much larger, multicenter studies? Although randomized, this was a small, single-center study with 1 endoscopist performing all the procedures. Second, where does EUS-CD fit in with respect to other EUS-guided rescue procedures such as EUS-rendezvous (where EUS puncture of the bile duct is performed and a wire is passed antegrade through the papilla so that conventional ERC can be performed) or EUS access to intrahepatic ducts through the stomach?21 In addition, when the papilla is accessible, should EUS-CD be considered before needle-knife precut sphincterotomy? Third, can EUS-CD be used in patients for whom resectability is uncertain, or will it make a surgeon’s task more difficult? Fourth, what is the optimal technique (Should a needle-knife be used? What should be the optimal size of the dilating catheter and/or balloon? Should a partially covered SEMS be utilized or a fully covered one?), and should we wait for better-designed scopes (eg, forward-viewing echoendoscope) or devices specifically tailored to this novel procedure (eg, shorter stents designed to better appose the duodenal and biliary walls)?
Despite all these questions, I have no doubt that EUS will have an increasingly important role in biliary access for malignant disease in the very near future, as many of us are already using some of these techniques (or seriously considering them) in select situations. Similar to the history of many endoscopic procedures including upper gastrointestinal endoscopy, colonoscopy, and ERCP, we have seen EUS transform, in a relatively short period of time, from a purely diagnostic procedure to a technology that is offering an increasing array of therapeutic possibilities such as fine-needle injection, pancreatic pseudocyst drainage, pancreaticobiliary access and stenting, and radiofrequency ablation. For a procedure whose future relevance and utility was questioned by many gastroenterologists not too long ago, EUS has surely arrived at the party.
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