Joseph E. Geenen

The Efficacy of Endoscopic Sphincterotomy after Cholecystectomy in Patients with Sphincter-of-Oddi Dysfunction

Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction.

Risk factors for post-ERCP pancreatitis: a prospective multicenter study.

OBJECTIVES:Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study.METHODS:A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24–72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria.RESULTS:Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), ≥2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis.CONCLUSION:This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.

Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis

BACKGROUND Chronic pancreatitis in its early stages may defy diagnosis despite existing diagnostic modalities. Endoscopic retrograde pancreatography (ERCP), secretin test, and conventional ultrasound are insensitive in detecting the early stages of chronic pancreatitis. The aim of this study was to determine whether endoscopic ultrasonography (EUS) high-resolution imaging allows for the detection of chronic pancreatitis as compared with clinical history, ERCP, and secretin test. METHODS Eighty consecutive patients with recurrent pancreatitis underwent ERCP, EUS, and secretin test. EUS evaluated parenchymal changes: echogenic foci (calcification), prominent interlobular septae (fibrosis), small cystic cavities (edema), lobulated outer gland margin (fibrosis/atrophy), and heterogeneous parenchyma; and ductal changes: dilation, irregularity, echogenic wall (fibrosis), side-branch ectasia, and echogenic foci (stones). EUS criteria for chronic pancreatitis included mild (1 to 2 features), moderate (3 to 5 features), and severe (more than 5 features). RESULTS Abnormal studies were EUS = 63, ERCP = 36, and secretin test = 25. Secretin test had 100% agreement with normal and severe chronic pancreatitis by EUS criteria, but agreement was poor for mild (13%) and moderate (50%) disease. Alternatively, the agreement between ERCP- and EUS-specific criteria was excellent for normal (100%), moderate (92%), and severe (100%) chronic pancreatitis and poor for mild (17%) disease. When the 2-test modality (ERCP and secretin test) was compared with EUS alone, no enhancement in agreement was seen. CONCLUSION Using the above criteria EUS may assist in the diagnosis of chronic pancreatitis not established by ERCP or secretin test. Excellent agreement can be expected between EUS and ERCP in the diagnosis of chronic pancreatitis with the exception of mild changes noted on EUS (kappa statistics = 0.82: 95% CI [0.70, 0.95]). Long-term follow-up of the patients with mild EUS changes will determine the validity of EUS in diagnosing the early stages of chronic pancreatitis.

Incidence and risk factors for biliary and pancreatic stent migration

Endoprostheses are commonly used in the treatment of biliary and pancreatic disorders. The frequency of and potential risk factors for stent migration, however, remain largely unknown. From January 1986 to June 1990, 807 biliary and pancreatic stents were placed at our institution. Our study analyzed the occurrence of stent migration among the 589 stents for which follow-up data were available. Results demonstrated incidence rates of 4.9 and 5.9% for proximal (into the duct) and distal (out of the duct) biliary stent migration, respectively. Likewise, incidence rates of 5.2 and 7.5% were observed for proximal and distal pancreatic stent migration, respectively. Malignant strictures, larger diameter stents, and shorter stents were significantly associated with proximal biliary stent migration. Sphincter of Oddi dysfunction and longer stents were associated with proximal pancreatic stent migration. Migration of stents out of the common bile duct occurred more frequently in papillary stenosis. No other significant risk factors for distal migration were found. These results indicate that stent migration is an important complication. Multiple risk factors were associated with stent migration and need to be considered in the development of new stent types.

Treatment of pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct endoprosthesis

BACKGROUND Endoscopic treatment of pancreatic pseudocysts via cystenterostomy has been recognized as a successful treatment option in carefully selected patients. Pancreatic transpapillary stenting as an alternative treatment option in patients with pancreatic pseudocysts directly communicating with the main duct has received little consideration. The aim of the current study was to assess the safety and utility of transpapillary pancreatic endoprosthesis in the treatment of communicating pseudocysts. METHODS Twenty-one patients underwent placement of 33 transpapillary endoprostheses for the treatment of symptomatic pancreatic pseudocysts. All pseudocysts communicated with the main pancreatic duct and ranged in size from 3 to 9 cm (mean 6 cm). Eight patients had associated pancreatic duct strictures. RESULTS Stent placement was successful in all cases: 13 directly into the pseudocyst, 8 beyond the stricture but not into the pseudocyst. Initial resolution of pseudocysts was seen in 17 patients, with 16 patients free of pseudocyst recurrence at mean follow-up of 37 months. All patients with associated strictures were treated successfully. Factors predictive of success included presence of strictures, size of pseudocyst greater than or equal to 6 cm, location in the body of the pancreas, and duration of pseudocyst less than 6 months. Complications included one episode of mild pancreatitis. CONCLUSIONS Endoscopic treatment of symptomatic pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct stenting is a safe, effective modality and should be considered a first line therapy.

Endoscopic therapy in patients with pancreas divisum and acute pancreatitis a prospective randomized controlled clinical trial

Endoscopic endoprosthesis (stent) placement across the minor papilla has been shown to be beneficial in reducing abdominal pain and episodes of pancreatitis in a small group of patients with pancreas divisum and acute recurrent pancreatitis. In a randomized, controlled clinical trial, 19 patients with pancreas divisum and at least 2 documented episodes of pancreatitis were randomized to either dorsal duct stent placement (10 patients--5 women and 5 men) or controls (9 patients--6 women and 3 men). All other causes of pancreatitis were excluded. Patients were followed at 4-month intervals for evaluation and/or stent exchange during a 1-year period. The following criteria were evaluated during follow-up: number of hospitalizations or emergency room visits, the number of documented episodes of pancreatitis, and gradation of the patients overall general feeling based on a visual analog scale. Mean follow-up times in the stent and control groups were 28.6 and 31.5 months, respectively (p greater than 0.05, NS). No patients in the stent group required hospitalization or emergency room visits for abdominal pain only during and following the treatment period. However, in the control group there were five hospitalizations and two emergency room visits for abdominal pain during a similar period (p less than 0.05). Pancreatitis was documented with an elevated amylase twice the normal range, one time in the stent group and seven times in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter, 4-Week, Double-Blind, Randomized, Placebo-Controlled Trial of Lubiprostone, a Locally-Acting Type-2 Chloride Channel Activator, in Patients With Chronic Constipation

OBJECTIVES:To assess the efficacy and safety of lubiprostone in adults with chronic constipation.METHODS:This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements (SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement (BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/discomfort; global treatment effectiveness ratings; and safety assessments.RESULTS:The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients (5.69 vs 3.46, P = 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 (P ≤ 0.002). Within 24 h of the first dose of study drug, 56.7% of those given lubiprostone reported a SBM compared with 36.9% of those given placebo (P = 0.0024); within 48 h, 80% and 60.7% of these patients reported a SBM (P = 0.0013), respectively. Stool consistency, straining, and constipation severity, as well as patient-reported assessments of treatment effectiveness, were significantly improved with lubiprostone compared with placebo at all weeks (P ≤ 0.0003). The two most common treatment-related adverse events were nausea (31.7%) and headache (11.7%).CONCLUSIONS:In patients with chronic constipation, treatment with lubiprostone produces a BM in the majority of individuals within 24–48 h of initial dosing and improves the frequency as well as other characteristics associated with BMs with short-term (i.e., 4 wk) treatment. The most commonly reported adverse event was mild to moderate nausea, which resulted in treatment discontinuation in 5% of treated patients.

Treatment of symptomatic distal common bile duct stenosis secondary to chronic pancreatitis: comparison of single vs. multiple simultaneous stents

BACKGROUND Common bile duct stenosis occurs in up to 30% of patients with chronic pancreatitis. Most such stenoses are found incidentally during ERCP, but others manifest as obstructive jaundice, recurrent cholangitis, secondary biliary cirrhosis, or choledocholithiasis. Operative drainage has been the main treatment despite the potentially high morbidity in patients with chronic pancreatitis. Endoscopic biliary drainage with a single stent has been successful in the short term. The aim of this study was to determine the long-term benefit of a single stent vs. multiple simultaneous stents for treatment of patients with chronic pancreatitis and symptoms because of distal common bile duct stenosis. METHODS Twelve consecutive patients with chronic pancreatitis and common bile duct stenosis underwent endoscopic placement of multiple simultaneous stents and were followed prospectively (Group II). Results were compared with a group of 34 patients in whom a single stent was placed before the start of the present study (Group I). All 46 patients (35 men, 11 women; age range 30-71 years) had chronic pancreatitis and common bile duct stenosis, and presented with symptoms indicative of obstruction (abdominal pain, jaundice, elevated biochemical tests of liver function, acute pancreatitis, cholangitis). The 34 patients in Group I had single stent (10F, 7-9 cm) placement, with exchange at 3 to 6 month intervals (1-4 exchanges) over a mean of 21 months. The 12 patients in Group II underwent placement of multiple simultaneous stents at 3-month intervals (single 10F stents added sequentially) over a mean of 14 months. Mean follow-up was 4.2 years in Group I and 3.9 years for Group II. Factors assessed included symptoms, biochemical tests of liver function, diameter of common bile duct stenosis, and complications. RESULTS In Group I, (34 patients), a total of 162 single stent placement/exchanges were performed (mean 5/patient). In Group II (12 consecutive patients), 8 patients had 4 (10F) stents placed simultaneously, and 4 patients had 5 (10F) stents. At the end of the treatment period, near normalization of biochemical tests of liver function was observed for all patients in Group II, whereas only marginal benefit was noted for patients in Group I. Four patients in Group I had recurrent cholangitis (6 episodes), whereas no patient in Group II had post-procedure cholangitis. In the 12 patients with multiple stents, distal common bile duct stenosis diameter increased from a mean of 1.0 mm to 3.0 mm after treatment; no change in diameter was noted in patients treated with a single stent. CONCLUSIONS Distal common bile duct stenosis secondary to chronic pancreatitis can be treated long term by stent placement. Multiple, simultaneous stents appear to be superior to single stent placement and may provide good long-term benefit. The former resulted in near normalization of biochemical tests of liver function and an increase in distal common bile duct diameter. Multiple stent placement may obviate the need for surgical diversion procedures.

Preliminary experience with endoscopic stent placement in benign pancreatic diseases

We treated 35 patients with endoscopic stent placement across the major or minor papilla in an attempt to relieve suspected partial obstruction to pancreatic duct drainage in patients with pancreatitis. The patients subsequently have been followed for periods ranging from 6 months to 3 years (mean, 14 months). Endoscopic stents were successfully placed across the minor papilla in 19 of 22 patients with pancreas divisum associated with acute recurrent pancreatitis (19) and severe abdominal pain (3). 17 patients had symptomatic improvement manifested by a decrease in frequency of attacks of pain and emergency admission. Stents were placed through the major papilla in 14 of 15 patients with recurrent pancreatitis related to a variety of causes. 8 of the 14 patients improved during the follow-up period, including 4 of 5 patients with alcoholic pancreatitis complicated by a segmental stricture.

Idiopathic recurrent pancreatitis

The cause of recurrent acute pancreatitis can be identified in the majority of patients. A small group of patients in whom an etiological association is not obvious is characterized as idiopathic recurrent pancreatitis (IRP). During the last seven years, we used endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi (SO) manometric pressure studies to investigate 116 patients initially diagnosed as IRP. Forty-four of the 116 patients were found to have a demonstrable cause of their pancreatitis. Appropriate therapeutic intervention was carried out in 43 of these patients with a favorable outcome in the majority of patients noted during long-term follow-up.