Clinical Advances in Biliary and Pancreatic Disorders

John Baillie, MB, ChB, FRCP, FASGE

Disclosures

May 21, 2008

Does Sildenafil Reduce Sphincter of Oddi Pressure in Patients Undergoing ERCP for Suspected Sphincter of Oddi Dysfunction?


San Diego, California; Tuesday, May 20, 2008 -- A number of interesting and innovative studies on biliary and pancreatic disorders were presented during this year's Digestive Disease Week (DDW) meeting. This report reviews some of the more clinically relevant of these data, with a view toward the potential implications for practice.

Sphincter of Oddi dysfunction (SOD) is one of the most difficult conditions that gastroenterologists are called upon to investigate and treat. Thus far, no agent has been identified that will reliably and consistently relax a normotensive or hypertensive SO. Sildenafil is a phosphodiesterase-5' inhibitor whose actions are exerted through nitric oxide-mediated messenger pathways. It has major inhibitory effects on gastrointestinal smooth muscle. Sildenafil is best known for its role in the treatment of male erectile dysfunction. However, due to its action through the nitric oxide system, it seemed likely that this agent would also affect SO pressure. The authors studied 7 patients (6 women, 1 man; age range, 31-57 years) with an intact SO and suspected SOD.[1] They excluded: patients younger than 18 years and older than 65 years; those who had a difficult cannulation; patients with prior post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis; those with American Society of Anesthesiologists (ASA) grade ≥ 3, those who had used sildenafil within 7 days; patients with creatinine clearance < 30 mL/min; and pregnant women. Results revealed that administration of sildenafil markedly reduced basal SO pressure in patients with suspected SOD. Pre- and posttreatment pressures were 82 ± 52 and 29 ± 27 mm Hg, respectively. The mean reduction in pressure was an impressive 53 ± 40 mm Hg.

These findings are intriguing, and further studies using this agent are certainly warranted. The authors did not provide data on patients' symptomatic response to sildenafil. We need to know whether the SO-relaxing properties of this drug translate into meaningful symptomatic relief from right upper quadrant abdominal pain, and if so, for how long. Additionally, will sildenafil also enhance the sex lives of the mainly female SOD population? The authors did not offer an opinion. This study is likely to spawn larger and better (in terms of quality-of-life evaluation) investigations that may have an impact on this very difficult-to-manage condition.

ERCP Technology: Advancements in Intraductal Visualization During Cholangioscopy

A number of abstracts presented during the biliary and pancreatic sessions at this year's DDW meeting addressed the utility of the new SpyGlass Direct Visualization System (Boston Scientific; Natick, Massachusetts) for peroral cholangioscopy. In the past, cholangioscopy during ERCP has been burdensome due to the need for at least 2 endoscopists, bulky instruments, and all-too-often incompatible accessories. This new visualization system overcomes many of these limitations. However, because this device is an expensive addition to any endoscopy unit's armamentarium, numerous investigations are being conducted to identify potential applications.

In a study presented during DDW 2008,[2] investigators assessed the feasibility and efficacy of this single-operator duodenoscope assisted cholangiopancreatoscopy system in the treatment of main pancreatic duct stones in chronic pancreatitis. Between July and November 2007, 16 procedures were performed with this visualization system, 8 for manifestations of chronic pancreatitis. Two of these 8 patients underwent evaluation of the bile duct and 6 underwent pancreatoscopy; 5 of these 6 had calcification of the pancreatic ductal system, and 4 of these 5 had successful contact lithotripsy with stone removal. However, sometimes more than 1 ERCP procedure was necessary to complete the stone clearance. The authors commented that the current size of the insertion catheter -- 10 Fr gauge -- limits the utility of the device, which was first developed for urologic procedures. There were no procedure-related complications.

A Texan group has amassed significant experience with this technology. In a study presented during this year's meeting,[3] 128 patients (71 men, 57 women; mean age, 57.6 years) underwent evaluation using this novel direct visualization system. Indications and routing were diagnostic in 44% of cases, therapeutic in 56%, peroral in 12%, and percutaneous in 7%. Therapeutic indications included common bile duct stones (47), pancreatic duct stones (6), and biliary strictures (25). There was no associated morbidity or mortality. The optics of this single-operator miniature endoscope were reportedly degraded after about 10 uses. Successful contact lithotripsy was performed in 40 of 47 patients. In 5 cases, the electrohydraulic probe could not be advanced due to angulation. In 3 of 6 attempts, pancreatic stones were successfully removed. The maneuverability of the device was improved by removing the guidewire. The diagnosis of a biliary stricture was modified in 20 of 29 cases and confirmed in 10 of 23. Diagnoses based on abnormal abdominal imaging and laboratory tests were modified in 43 of 63 cases. Of 3 patients who underwent cholangiocarcinoma staging, 2 were found to have multicentric disease.

Failure Is Not an Option

In these days of managed healthcare in the United States, cost containment is all important. In this context, a group from Alabama looked at the cost of failure to complete an ERCP procedure. In this retrospective study conducted over a 30-month period,[4] 65 of 1814 (3.6%) patients had a failed ERCP; 30 patients were excluded from analysis for a variety of reasons. The indications for the subsequently failed procedures included obstructive jaundice (21), pancreatitis (10), abdominal pain (3), and abnormal liver tests (1). Among the 21 patients with biliary obstruction, ERCP failure was managed by surgical bypass in 2, repeat ERCP in 4, percutaneous transhepatic cholangiography and drainage (PTC+D) in 14, and no intervention in 1 terminally ill patient. PTC+D was successful in 11 of 14 patients, was completed using endoscopic "rendezvous" in another 2 patients, and failed in 1. Complications included perioperative myocardial infarction (1), cholangitis after PTC+D (1), mild-to-moderate pancreatitis (6), and fever (1). The complication rate among the 105 matched-control patients was no different among the cases (5.7%). When compared with controls, the cost of failure to complete an ERCP was not insignificant ($1458 vs $5668) and 216 of 1814 ERCPs (11.9%) performed during this study had failed previously at outside hospitals. The authors succeeded in completing ERCP in 95% of patients. For expert endoscopists in referral centers, failure to complete an ERCP is uncommon but not unknown. Appropriate radiologic and surgical back-up ensure that these cases are completed without significant added morbidity or mortality.

More on ERCP Complications

Perforations should be a rare complication of ERCP. However, when they do occur, early recognition and aggressive management are essential to limit morbidity and mortality. This large retrospective study sought to identify the clinical factors that affected outcome in patients who suffered an ERCP-related perforation.[5] During the study period a total of 4109 ERCPs had been performed, and 47 (1.1%) patients had suffered an ERCP-related performation (1.1%). The mean hospitalization stay was 16.1 days (range, 1-81). Thirty-two of the 47 patients were female. The main indications for ERCP in these perforation cases were SOD (38%), pancreatitis (28%), and obstructive jaundice (25%). Interventions associated with perforation included pre-cutting (6.3%), endoscopic sphincterotomy (75%), stenting (47%), SO manometry (10.5%), and stone extraction (6.3%). Factors shown to increase hospital length of stay included delayed detection of perforation (> 24 hours); initial clinical /laboratory signs of fever, increased white blood count, and abdominal tenderness; presence of retroperitoneal fluid on initial computed tomography scan; and the development of local fluid collection or ascites.

It is well worth noting that the odds ratio of a perforation occurring in the setting of SOD was 40, another good reason -- if any was needed -- to refer patients with SOD to experts for their management. The 1.1% ERCP-related perforation rate is higher than some previous studies have reported. It would be interesting to know whether this reflects the increasingly therapeutic (and diminishing diagnostic) use of ERCP in modern hepatobiliary and pancreatic disorders practice.

Modeling the Cost-Effectiveness of Imaging Techniques for Bile Duct Stones

In a study using decision-tree simulation, investigators from Montreal, Quebec, Canada, looked at 4 potential strategies for identifying suspected bile duct stones[6]:

  • ERCP alone;

  • Magnetic resonance cholangiopancreatography (MRCP) then ERCP (if a stone was found);

  • Endoscopic ultrasound (EUS) then ERCP (if a stone was found) on a separate day; and

  • EUS then ERCP (if a stone was found) on the same day.

The authors concluded that:

  • Both clinical and laboratory data should be used to stratify patients at risk for common bile duct stones;

  • MRCP, combined EUS/ERCP, and ERCP alone are all cost-effective strategies;

  • MRCP-first strategies should be reserved for cases with low probability of a stone, and ERCP-first approaches should be reserved for cases with high probability;

  • The "EUS then ERCP on a separate day" strategy is unlikely to be cost-effective, whereas the strategy of "EUS then ERCP on the same day" is likely to be cost-effective; and

  • The clinical and economic consequences of small and asymptomatic stones detected by EUS are unknown and merit further study.

The authors are to be congratulated on "getting their arms around" a large and cumbersome dataset to show clinicians how they might tackle a common clinical problem (suspected bile duct stones) in a cost-effective manner.

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