Evaluation of recombinant platelet-activating factor acetylhydrolase for reducing the incidence and severity of post-ERCP acute pancreatitis.

BACKGROUND: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. Platelet-activating factor (PAF) has been implicated in the pathophysiologic events associated with acute pancreatitis. Animal and human studies suggested that recombinant PAF acetylhydrolase (rPAF-AH) might ameliorate the severity of acute pancreatitis. OBJECTIVE: Our purpose was to determine whether prophylactic rPAF-AH administration reduces the frequency or severity of post-ERCP pancreatitis in high-risk patients. DESIGN: Randomized, multicenter, double-blind, placebo-controlled study. INTERVENTIONS: Patients received rPAF-AH at a dose of either 1 or 5 mg/kg or placebo. Patients were administered a single intravenous infusion over 10 minutes of study drug or placebo <1 hour before ERCP. MAIN OUTCOME MEASUREMENTS: Standardized criteria were used to diagnose and grade the severity of post-ERCP pancreatitis. Adverse events were prospectively recorded. RESULTS: A total of 600 patients were enrolled. There were no statistically significant differences among the treatment groups with respect to patient demographics, ERCP indications, and patient and procedure risk factors for post-ERCP pancreatitis with the following exceptions: the rPAF-AH 5 mg/kg group had significantly fewer patients younger than 40 years old and scheduled to undergo a therapeutic ERCP involving the pancreatic sphincter or duct. Post-ERCP pancreatitis occurred in 17.5%, 15.9%, and 19.6% of patients receiving rPAF-AH (1 mg/kg), rPAF-AH (5 mg/kg), and placebo, respectively (P = .59 for rPAF-AH 1 mg/kg vs placebo and P = .337 for rPAF-AH 5 mg/kg vs placebo). There was no statistically significant difference between the groups with regard to the severity of pancreatitis, frequency of amylase/lipase elevation more than 3 times normal, or abdominal pain. CONCLUSIONS: There was no apparent benefit of rPAF-AH treatment compared with placebo in reducing the incidence of post-ERCP pancreatitis in subjects at increased risk.

Non-surgical tissue biopsy among patients with advanced pancreatic cancer: effect on survival.

OBJECTIVE: The aim was to determine the survival of patients with advanced, unresectable pancreatic cancer in relation to whether they underwent nonsurgical biopsy of their primary tumor. METHODS: A total of 1481 patients with distant stage pancreatic cancer diagnosed between 1992 and 2001 who underwent radiation treatment but not cancer-directed surgery were analyzed. The design is a retrospective cohort study from the Surveillance, Epidemiology, and End Results program of the US National Cancer Institute. Survival curves were created using Kaplan-Meier method and compared via log-rank test. RESULTS: Of 1481 patients (median age, 66 years) included in our analysis, 1406 (95%) underwent nonsurgical biopsy (95%) and 75 (5%) did not. There was no statistically significant difference in overall median survival according to receipt of nonsurgical biopsy (Kaplan-Meier curve, log-rank test = 0.09). A subgroup analysis of patients younger than 65 years who did not undergo biopsy revealed a hazard ratio of 1.76 (95% confidence interval, 1.14-2.72); that is, there was a 76% higher hazard for death among younger patients who did not undergo biopsy compared with those who did (P = 0.011). CONCLUSION: Nonsurgical biopsy did not seem to negatively impact survival among patients with advanced pancreatic cancer.

Mechanical lithotripsy of pancreatic and biliary stones: complications and available treatment options collected from expert centers.

INTRODUCTION: PD and common bile duct (CBD) stones often require mechanical lithotripsy (ML) at ERCP for successful extraction. The frequency and spectrum of complications is not well described in the literature. AIM: To describe the frequency and spectrum of complications of ML. METHODS: A comprehensive retrospective review of cases requiring ML of large or resistant PC and/or CBD stones using a 46-point data questionnaire on type(s) of complication, treatment attempted, and success of treatment. The study involved 7 tertiary referral centers with 712 ML cases (643 biliary and 69 pancreatic). RESULTS: Overall incidence of complications were: 4-4% (31/712); 23/643 biliary, 8/69 pancreatic; 21 single, 10 multiple. Biliary complications: trapped (TR)/broken (BR) basket (N = 11), wire fracture (FX) (N = 8), broken (BR) handle (N = 7), perforation/duct injury (N = 3). Pancreatic complications: TR/BR basket (N = 7), wire FX (N = 4), BR handle (N = 5), pancreatic duct leak (N = 1). Endoscopic intervention successfully treated complications in 29/31 cases (93.5%). Biliary group treatments: sphincterotomy (ES) extension (N = 7), electrohydraulic lithotripsy (EHL) (N = 11), stent (N = 3), per-oral Soehendra lithotripsy (N = 8), surgery (N = 1), extracorporeal lithotripsy (N = 5), and dislodge stones/change basket (N = 4). Pancreatic group treatments: ES extension (N = 3), EHL (N = 2), stent (N = 5), Soehendra lithotriptor (N = 4), dislodge stones/change basket (N = 2), extracorporeal lithotripsy (ECL) (N = 1), surgery (N = 1). Perforated viscus patient died at 30 days. CONCLUSION: The majority of ML in expert centers involved the bile duct. The complication rate of pancreatic ML is threefold greater than biliary lithotripsy. The most frequent complication of biliary and pancreatic ML is trapped/broken baskets. Extension of ES and EHL are the most frequently utilized treatment options.

Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience.

BACKGROUND: Accurate assessment of pancreatic cystic neoplasms is imperative before selecting available treatment options, such as surgical resection, drainage, or conservative therapy. Available modalities, CT and magnetic resonance imaging, have been inconsistent in diagnosis. Reports involving EUS and cyst fluid analysis have been encouraging, including studies of EUS features and/or cyst fluid analysis, which may differentiate pancreatic cystic neoplasms. OBJECTIVE: To retrospectively determine cyst fluid characteristics that differentiate cystic neoplasms. DESIGN: Patient evaluation included (1) EUS features (reported elsewhere) and (2) cyst fluid analysis (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA 19-9], amylase and lipase, viscosity [VIS], mucin stain, and cytology). Exclusion criteria included the following: intraductal papillary mucinous tumor lesions, bloody cyst aspirate, neuroendocrine tumors, and patients without surgical histopathology. SETTING: Pancreatic Biliary Center, St Luke's Medical Center, Milwaukee, Wisconsin. PATIENTS: A total of 102 patients (60 women, 42 men; age, 23-76 years) presented for evaluation of pancreatic cystic neoplasm; 71 underwent surgical resection. RESULTS: Seventy-one of 102 patients who underwent surgery presented the following histopathologic correlates: 23 pseudocysts (PC), 13 serous cystadenoma (SCyA), 21 mucinous cystadenoma (MCyA), and 14 mucinous cystadenocarcinoma (MCyA-CA). Cyst fluid analysis of these patients showed the following: VIS was lower in PC (mean, 1.3) and SCyA (1.27) when compared with MCyA (1.84) and MCyA-CA (1.9). All mucinous neoplasms had VIS >1.6, whereas only 2 mucinous cystic neoplasms (MCN) had VIS = 1.6 (both PC). The CEA level was significantly higher in MCyA (adenoma [878 ng/mL], carcinoma [27,581 ng/mL]) vs PC (189 ng/mL), and SCyA (121 ng/mL). Amylase levels were higher in PC (7210 U/L) compared with cystic neoplasm (SCyA, 679 U/L; MCyA, 1605 U/L; MCyA-CA, 569 U/L). CONCLUSIONS: Differential diagnosis of pancreatic cystic neoplasm is significantly enhanced by cyst fluid analysis. Elevated CEA (> or =480 ng/mL) and VIS (>1.6) accurately predict MCN from SCyA and PC. Malignant from benign MCN can be differentiated by CEA levels > or =6000 ng/mL.

Primary sclerosing cholangitis treated by endoscopic biliary dilation: review and long-term follow-up evaluation.

Primary sclerosing cholangitis (PSC) is an important cause of chronic liver disease. We review the management of PSC and report a 20-year follow-up of our initial 10 patients. This is the longest detailed follow-up of a group of PSC patients to date. We discuss the clinical course and results of endoscopic management in these patients and relate these data to management of PSC in general. We compare the actual survival of these patients to predicted survival scores based on the Mayo multicenter survival model. Although our patients presented with cholangitis, which typically reflects advanced stages of liver disease, their survival compares favorably with expected survival in unselected PSC patients. Endoscopic balloon dilation of PSC patients presenting with biliary strictures and cholangitis may have long-term benefit in addition to short-term symptomatic relief.

The underutilization of EUS-guided FNA in the lymph-node staging of non-small-cell lung cancer: perceptions of chest physicians in Wisconsin.

BACKGROUND: Recently, the American College of Chest Physicians (ACCP) published evidence-based guidelines for the invasive staging of non-small-cell lung cancer (NSCLC), which shows the potential value of transesophageal sampling by EUS-guided FNA (EUS-FNA). The objective of the study was to determine the perceptions and the clinical practice of chest physicians regarding EUS-FNA as a staging modality for NSCLC. METHODS: We mailed a questionnaire to all members of the ACCP in Wisconsin. RESULTS: Seventy-one of 173 members (41%) responded. Chest physicians were more likely to perceive positron emission tomography, transbronchial needle aspiration, transthoracic needle aspiration, and mediastinoscopy to be able to make a difference in managing patients with NSCLC instead of EUS-FNA (p=0.01). Of the 40 chest physicians who believed that EUS-FNA can change the management of NSCLC, only 8 (20%) have sent a patient for EUS-FNA in the past year. Our findings may not necessarily reflect the opinions of chest physicians in other areas of the United States. CONCLUSIONS: Many of the chest physicians surveyed do not believe EUS-FNA impacts the management of NSCLC. This limited awareness may represent a barrier to successful utilization of EUS-FNA in lung-cancer staging.

Oral allopurinol does not prevent the frequency or the severity of post-ERCP pancreatitis.

BACKGROUND: Pancreatitis is the most common major complication of ERCP. Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this trial was to determine whether prophylactic allopurinol, an inhibitor of oxygen-derived free radical production, would reduce the frequency and severity of post-ERCP pancreatitis. Methods A total of 701 patients were randomized to receive either allopurinol or placebo 4 hours and 1 hour before ERCP. A database was prospectively collected by a defined protocol on patients who underwent ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. RESULTS: The groups were similar with regard to patient demographics and to patient and procedure risk factors for pancreatitis. The overall incidence of pancreatitis was 12.55%. It occurred in 46 of 355 patients in the allopurinol group (12.96%) and in 42 of 346 patients in the control group (12.14%; p = 0.52). The pancreatitis was graded mild in 7.89%, moderate in 4.51%, and severe in 0.56% of the allopurinol group, and mild in 6.94%, moderate in 4.62%, and severe in 0.58% of the control group. There was no significant difference between the groups in the frequency or the severity of pancreatitis. CONCLUSIONS: Prophylactic oral allopurinol did not reduce the frequency or the severity of post-ERCP pancreatitis.

Intrapancreatic ductal pressure in sphincter of Oddi dysfunction.

OBJECTIVES: It is widely believed that sphincter of Oddi dysfunction (SOD) induces pancreatitis through an increase in intrapancreatic ductal pressure. Animal models have demonstrated that increased intrapancreatic ductal pressure plays a role in the development of pancreatitis. The role of intrapancreatic ductal pressure in SOD-induced pancreatitis has not been investigated in humans. The present study sought to (1) investigate the effect of SOD on intrapancreatic ductal pressure and (2) identify the correlation between elevated intrapancreatic ductal pressure and the presence of pancreatitis. METHODS: A total of 263 patients presenting with abdominal pain, acute recurrent pancreatitis, or chronic pancreatitis were studied. Intrapancreatic ductal pressure was measured blindly. Subsequently complete SOM was performed in standard fashion. RESULTS: Intrapancreatic ductal pressure correlated significantly with sphincter of Oddi (SO) basal pressure (correlation coefficient: 0.39, P < 0.01). Individuals with SOD had a significantly higher pressure (19.6 +/- 15.9 mm Hg) as compared with those with normal SO motility (11.1 +/- 7.9 mm Hg) (P < 0.001). This significant difference was observed in all subgroups (recurrent abdominal pain, acute recurrent pancreatitis, and chronic pancreatitis) (P < 0.01). Patients with acute recurrent pancreatitis or chronic pancreatitis did not show a significant elevation in their intrapancreatic ductal pressures when compared with those with recurrent abdominal pain alone. CONCLUSIONS: SOD leads to an increase in intrapancreatic ductal pressure. Increased PD pressure is not the sole determinant for the development of pancreatitis.

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.

Endoscopic transpancreatic papillary septotomy for inaccessible obstructed bile ducts: Comparison with standard pre-cut papillotomy.

BACKGROUND: Access to the pancreatic or the bile duct is paramount to the success of diagnostic and therapeutic ERCP. Selective cannulation may be difficult because of the small size of the papilla and anatomic factors such as peripapillary diverticulum and gastrectomy with Billroth-II anastomosis. Currently, one of the techniques for gaining access in such cases is the pre-cut technique with a catheter that has a thin wire at the tip (needle knife). A less well-described pre-cut technique involves initial cannulation of the pancreatic duct with a "traction-type" papillotome and then incision through the "septum" toward the bile duct. The aim of this randomized trial was to compare the success and the complication rates of needle-knife sphincterotomy and transpancreatic sphincterotomy in achieving cannulation of an otherwise inaccessible bile duct. METHODS: Sixty-three consecutive patients with inaccessible bile ducts underwent pre-cut sphincterotomy either by needle-knife sphincterotomy (n = 34) or transpancreatic septotomy (n = 29). In patients with an accessible pancreatic duct who undergo needle-knife sphincterotomy, a short (2-3 cm) stent (5F-7F) was placed in the pancreatic duct to act as a guide and to reduce the risk of post-procedure pancreatitis. All patients were hospitalized overnight for observation after pre-cut sphincterotomy. The outcomes measured were success rate and complications. Indications for pre-cut sphincterotomy were the following: suspected choledocholithiasis, 11 patients (17.5%); obstructive jaundice with negative CT findings, 19 patients (29.2%), or with positive CT findings, 13 patients (20.6%); abdominal pain with elevated biochemical tests of liver function, 15 patients (23.8%); and miscellaneous, 5 patients (7.9%). RESULTS: In 55 of 63 (87%) patients, the bile duct was selectively cannulated after pre-cut sphincterotomy. On a pre-protocol basis, the bile duct was cannulated in 29 of 29 (100%) patients randomized to transpancreatic septotomy sphincterotomy and 26 of 34 (77%) patients who underwent needle-knife sphincterotomy (p = 0.01). There were 7 complications, including bleeding (n = 2) and acute pancreatitis (n = 5). Complications were less frequent in the transpancreatic septotomy sphincterotomy group (1/29; 3.5%) compared with the needle-knife sphincterotomy group (6/34; 17.7%). CONCLUSIONS: Transpancreatic pre-cut sphincterotomy can be performed with a high degree of success in patients with inaccessible obstructed bile ducts. Compared with standard needle-knife sphincterotomy, transpancreatic septotomy sphincterotomy has a significantly higher rate of bile duct cannulation and a lower complication rate.

Endoscopic management of adenoma of the major duodenal papilla.

BACKGROUND: It is well established that adenoma of the major duodenal papilla has a potential for malignant transformation. Standard treatment has been surgical (duodenotomy/local resection, pancreaticoduodenectomy). Endoscopic management is described, but there is no established consensus regarding the approach to papillectomy or the need for surveillance. This study describes endoscopic management and long-term follow-up of papillary tumors by 4 groups of expert pancreaticobiliary endoscopists. METHODS: Consecutive patients with papillary tumors referred to 4 pancreaticobiliary endoscopy centers for evaluation for endoscopic papillectomy were reviewed. For each patient, an extensive questionnaire was completed, which included 19 preoperative and 15 postoperative data points. A total of 103 patients (53 women, 50 men, age range 24-93) who underwent attempted endoscopic resection were included. Of these, 72 had sporadic adenoma, and the remaining patients had familial adenomatous polyposis, including Gardner's variant. Presenting symptoms were jaundice/cholangitis/pain (n=59), pancreatitis (n=18), and bleeding (n=12). Twenty-six patients were asymptomatic. RESULTS: Endoscopic treatment was successful, long term, in 83 patients (80%) and failed (initial failure or recurrent tumor) in 20 (20%) patients. Success was significantly associated with older age (54.7 [16.6] vs. 46.6 [21.7] years; p=0.08) and smaller lesions (21.1 [8.3] vs. 29.7 [7.2] mm; p<0.0001). Success rate was higher for sporadic lesions compared with genetically determined lesions (63 of 72 [86%] vs. 20 of 31 [67%]; p=0.02). There were 10 initial failures, which was more common for sporadic lesions (7 of 10). The overall success rate for papillectomy was similar in patients who had adjuvant thermal ablation (81%) compared with those who did not (78%). However, recurrence (n=10) was more common in the former group (9 of 10, [90%]; p=0.22). Complications (n=10) included acute pancreatitis (n=5), bleeding (n=2), and late papillary stenosis (n=3). Acute pancreatitis was more common in patients who did not have pancreatic duct stents placed (17% vs. 3.3%). Papillary stenosis was more frequent without short-term pancreatic duct stent placement (15.4% vs. 1.1%), although the difference was not statistically significant, because this complication was infrequent. CONCLUSIONS: Endoscopic treatment of papillary adenoma in selected patients appears to be highly successful. The majority can undergo complete resection after ERCP. In expert hands, complications are infrequent and may be avoided by routine placement of a pancreatic duct stent.

Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study.

BACKGROUND: Pancreatitis is the most frequent complication of ERCP. Injury to the papilla during ERCP could obstruct pancreatic duct outflow and initiate pancreatitis. A randomized prospective study was performed to evaluate the effect of pancreatic duct stent placement on the frequency and severity of post-ERCP pancreatitis in a selected group of patients. METHODS: The study group consisted of patients over 18 years of age at high risk for post-ERCP pancreatitis because of a difficult cannulation, sphincter of Oddi manometry, and/or the performance of endoscopic sphincterotomy. Patients were prospectively randomized to have a pancreatic duct stent placed or no stent upon completion of the ERCP. The endoprosthesis used was either a 5F nasopancreatic catheter or 5F, 2-cm long pancreatic stent. Study endpoints were the frequency and severity of post-ERCP pancreatitis. RESULTS: Patients undergoing pancreatic duct stent placement had a lower frequency of post-ERCP pancreatitis as compared with those in the control group (28% vs. 5%; p < 0.05). Pancreatitis tended to be less severe in patients who had pancreatic duct drainage. CONCLUSIONS: Pancreatic duct stent insertion after ERCP reduces the frequency of post-ERCP pancreatitis in patients at high risk for this complication.

"Tannenbaum" Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture.

BACKGROUND: Premature stent clogging is the major limitation with plastic stents used in the treatment of malignant biliary structures. A pilot study suggested improved duration of patency of the Tannenbaum stent compared with polyethylene stents. The aim of this prospective, multicenter randomized trial was to compare the Tannenbaum Teflon stent with a conventional polyethylene endoprosthesis (Cotton-Leung biliary stent set) for the treatment of malignant biliary strictures. METHODS: Patients over age 18 years with symptoms caused by nonhilar malignant biliary strictures were enrolled. Patients were randomized to receive a 10F Tannenbaum or polyethylene stent after a guidewire was passed beyond the stricture. One hundred six patients (mean age 72 years and 71 years, respectively) were enrolled (54 Tannenbaum, mean age 72 years; 52 polyethylene, mean age 71 years). RESULTS: Tannenbaum and polyethylene stent placement was successful in, respectively, 100% and 96% of procedures without complications. The mean (SD) 90-day stent patency of the Tannenbaum stent was 67% (7%) compared with 73% (7%) for the polyethylene stents. CONCLUSIONS: The present study demonstrated no difference in ease of implantation or stent patency between Tannenbaum and polyethylene stents.