A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). AIM: To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population. METHODS: This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules). RESULTS: Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed. CONCLUSIONS: Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.

The influence of variable-stiffness guide wires on basal biliary sphincter of Oddi pressure measured at endoscopic retrograde cholangiopancreatography.

BACKGROUND: Guide wires are commonly utilized to facilitate endoscopic procedures. However, their use may adversely influence the results of sphincter of Oddi manometry, thereby leading to erroneous diagnosis and therapy. The aim of this study was to evaluate the effect of guide wires on the basal pressure of the biliary sphincter of Oddi. METHODS: Forty-five consecutive patients with suspected sphincter of Oddi dysfunction were enrolled. Biliary sphincter of Oddi manometry was performed with and without a guide wire in the conventional retrograde fashion with a low-compliance infusion pump system, an aspirating catheter, and slow station pull-throughs. Three types of guide wires were studied: the Roadrunner (18 patients), the Glidewire (17 patients), and the standard Teflon guide wire (10 patients). The stiffness of the guide wires was tested and reported in Taber Stiffness Units (TSU; higher values represent greater stiffness). RESULTS: Biliary sphincter of Oddi manometry performed with a guide wire revealed higher basal pressure than the same measurement performed without a guide wire (52 +/- 33.4 mmHg vs. 34.4 +/- 20.5 mmHg; P = 0.001). Basal pressure changes induced by guide-wire use were highest in the Roadrunner group (32.9 +/- 33.9 mmHg), lowest in the standard Teflon group (11.6 +/- 8 mmHg; Roadrunner vs. standard Teflon: P = 0.02), and intermediate in the Glidewire group (17.1 +/- 22.1 mmHg). The use of a guide wire resulted in crossover from normal to abnormal basal pressure in 11 cases (Roadrunner, 7; Glidewire, 4) and from abnormal to normal in 2 (Roadrunner, 1; Glidewire, 1). Concordance between recordings obtained with and without guide wire was seen in 32 patients (71 %). Guide-wire stiffness was: Roadrunner: 0.74 TSU; Glidewire: 0.153 TSU; standard Teflon guide wire: 0.077 TSU. CONCLUSION: The use of guide wires frequently alters the basal biliary sphincter pressure, leading to incorrect diagnoses in approximately 40 % of cases. The basal pressure alterations depend on the stiffness of the guide wire used. Hence, the use of guide wires during sphincter of Oddi manometry is strongly discouraged.

Frequency of sphincter of Oddi dysfunction in patients with previously normal sphincter of Oddi manometry studies.

BACKGROUND AND STUDY AIMS: Sphincter of Oddi manometry (SOM), performed at endoscopic retrograde cholangiopancreatography (ERCP), is the gold standard for diagnosing sphincter of Oddi dysfunction (SOD). The question remains as to whether the short-term manometric recordings reflect the 24-hour pathophysiology of the sphincter. The aim of this study was to determine the frequency of SOD in persistently symptomatic patients with previously normal SOM studies. PATIENTS AND METHODS: All patients who underwent ERCP for suspected SOD over a 13-year period (1994 - 2007) were considered for inclusion in the study. Patients with an intact papilla and a previously normal SOM who had a repeat ERCP for persistent symptoms formed the study group. SOM was performed in conventional retrograde fashion. RESULTS: In all, 5352 patients without prior papillary intervention underwent SOM during the study period. A total of 1037 patients had normal SOM, and of these, 30 patients (27 female, mean age 40.1 years) underwent repeat ERCP for persistent symptoms. The median duration between the two ERCPs was 493.5 days (range 52-3538 days). In these 30 patients, SOD classification prior to the initial ERCP was: type I in one patient (not treated in 1994), type II in 17 patients, and type III in 12 patients. Of the 30 patients, 12 (40%) had normal SOM at repeat ERCP; SOD was diagnosed in 18/30 (60%) patients. CONCLUSIONS: A single SOM study may not represent the day-to-day physiology of the sphincter of Oddi; sphincter pathology may progress over time. One normal exam may not rule out SOD. A repeat ERCP with manometry may be warranted in a subset of patients with persistent debilitating symptoms and a high index of suspicion for SOD. Outcome data are needed to determine whether this approach justifies the potential risks of ERCP.

Multicenter comparative trial of the V-scope system for therapeutic ERCP.

BACKGROUND AND STUDY AIMS: A new duodenoscope (the V-scope), with a modified elevator used in combination with a dedicated short guide wire, constitutes the V-system. This system is intended to allow fixation of the guide wire at the elevator lever, thereby enhancing the speed and reliability of accessory exchange over a guide wire during ERCP. The aim of this study was to evaluate the extent to which the V-system provides improved efficiency in comparison with conventional duodenoscope and guide wire combinations. PATIENTS AND METHODS: This was an industry-sponsored multicenter randomized trial. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedures in which treatment was anticipated were randomly assigned to the V-system or to a conventional duodenoscope and accessories used routinely in each center. The parameters recorded included the total case time, fluoroscopy time, catheter/guide wire exchange time, guide wire repositioning, loss of guide wire access, and success or failure of guide wire fixation when using the V-system. RESULTS: Fifty patients were included, 22 in the conventional group and 28 in the V-system group. A total of 135 exchanges were carried out. The patients had up to six exchanges. The median exchange time was 19.4 s with the V-system and 31.7 s with the conventional systems ( P < 0.001). Guide wire repositioning was required less often in the V-system group ( P = 0.0005). The V-system effectively locked the guide wire in 63 of 71 exchanges (89 %). Loss of guide wire access occurred in two patients in the conventional group and four in the V-system group, attributable to failure to lock the guide wire early during the experience (no significant differences). CONCLUSIONS: The V-system can effectively secure the guide wire during accessory exchange in ERCP and reduces the time required to exchange accessories. This may enhance overall efficiency during ERCP.

Chemotherapy-induced sclerosing cholangitis.

AIM: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). METHODS: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. RESULTS: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n=1) or confluent fibrosis (n=0) were uncommon findings. CONCLUSION: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.

Recurrence rate of anastomotic biliary strictures in patients who have had previous successful endoscopic therapy for anastomotic narrowing after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: The development of anastomotic strictures is one of the most common complications of orthotopic liver transplantation (OLT) with choledochocholedochostomy anastomosis. Endoscopic therapy with balloon dilation and/or stent placement is an effective therapy. The aim of this study was to assess the recurrence rate of anastomotic strictures and the features that predict recurrence after previously successful endoscopic therapy. PATIENTS AND METHODS: We searched the endoscopic retrograde cholangiopancreatography (ERCP) database for all patients who had had an OLT who were undergoing ERCP. The study cohort consisted of post-OLT patients who had a recurrence of anastomotic stricture after initial resolution following a course of endoscopic therapy. RESULTS: A total of 916 OLT operations were performed during the study period from June 1994 to November 2004. Out of this group, 143 patients (15.6 %) were diagnosed with anastomotic stricture and underwent a total of 423 ERCPs for endoscopic treatment. Twelve patients who are still undergoing endoscopic therapy were excluded from the analysis. The technical success rate was 96.6 %, and the endoscopic therapy was successful in 82 % of patients; 18 % had a recurrence of cholestasis and ERCP revealed a recurrence of the anastomotic stricture that required intervention. The mean time of follow-up after stent removal was 28 months (range 1 - 114 months). The study did not reveal any clinical or endoscopic parameters that could predict recurrence, though the presence of a biliary leak at initial ERCP and a longer time to initial presentation were factors that showed a trend toward an increased likelihood of recurrence. CONCLUSIONS: Biliary strictures remain a common complication after OLT, and in nearly one in five patients these strictures recur after initially successful endoscopic therapy. There were no clinical or endoscopic parameters identified in this study that predicted recurrence. Further study is needed to determine what type of endoscopic therapy would minimize the risk of stricture recurrence.

Therapeutic biliary endoscopy.

Some steps of progress have been seen in the area of biliary therapeutic endoscopy, in the understanding and management of primary sclerosing cholangitis, problems relating to liver transplantation, malignant biliary strictures, and complications after endoscopic retrograde cholangiopancreatography, as well as sphincter of Oddi dysfunction. These topics are reviewed here.

Giant fibrovascular polyp of the esophagus.

The role of endoscopic ultrasound (EUS) in the diagnosis and management of a giant fibrovascular polyp of the esophagus in a 46-year-old woman is described here. The fibrovascular polyp was detected at esophagogastroduodenoscopy, and EUS demonstrated that it originated from the submucosa. EUS-guided fine-needle aspiration was performed, and cytological examination of the specimen revealed benign fibro-fatty elements. The lesion was resected via a transcervical esophagotomy. The literature on fibrovascular polyps is reviewed.

Therapeutic biliary endoscopy.

Some steps of progress have been seen in the area of biliary therapeutic endoscopy, in the understanding and management of primary sclerosing cholangitis, problems relating to liver transplantation, malignant biliary strictures, complications after endoscopic retrograde cholangiopancreatography, sphincter of Oddi dysfunction, and tissue sampling. The benefits (or lack thereof) of preoperative biliary drainage in the setting of malignant obstructive jaundice have received an extensive review.

Endoscopic augmentation of the cardia with a biocompatible injectable polymer (Enteryx) in a porcine model.

BACKGROUND: Endoscopic approaches to restore the gastroesophageal barrier in patients with gastroesophageal reflux disease (GERD) are presently undergoing clinical trial. The aim of the study was to demonstrate the feasibility, durability, safety, and antireflux efficacy following augmentation of the cardia with a biocompatible injectable polymer (Enteryx). METHODS: Augmentation was performed in 12 Yucatan mini-pigs. The cardia was injected circumferentially with 1-1.5 ml of Enteryx at three or four sites. Four groups of three animals each were killed at 2, 6, 12, and 24 weeks following augmentation. Gastrointestinal endoscopy and esophageal manometry were performed preoperatively and postoperatively. Competency was determined as the intragastric pressure (yield pressure) and volume (yield volume) needed during gastric distension with air and water to result in equalization of gastric and esophageal pressure. Comparisons were made with a group of noninjected animals (n = 6). RESULTS: All animals had a normal eating pattern; none showed any evidence of vomiting or regurgitation. The median injection volume was 4 ml (range, 1-8). At autopsy, implants were found in 83% of the animals. Intramuscular placement of the implant was durable, whereas sloughing occurred if the implant was placed submucosally. The mechanical properties of sphincter length and pressure were unaffected by the injection. The median yield pressure of the animals that survived for >6 weeks (21.4 mmHg) was significantly greater (p = 0.049) than the animals that survived for <6 weeks (4.5 mmHg) and greater (p = 0.054) than the control animals (9.1 mmHg), suggesting that the healing process was associated with reduced distensibility of the cardia. CONCLUSIONS: Augmentation of the cardia with an injectable polymer (Enteryx) is simple, safe, and durable. Early studies suggest that alteration in the distensibility and geometry of the gastroesophageal junction may provide antireflux protection.

Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone.

BACKGROUND AND STUDY AIMS: Patients with suspected or documented sphincter of Oddi dysfunction (SOD) who undergo standard biliary sphincterotomy have high rates of post-procedure pancreatitis. Approximately 75% of such patients have elevated basal pressures of the pancreatic sphincter. Biliary sphincterotomy (BES) on its own leaves the pancreatic sphincter unablated and may cause transient edema which aggravates the increase in pancreatic sphincter pressure. Combined pancreaticobiliary therapy (PBR), using pancreatic stenting in addition to sphincterotomy may therefore be safer. PATIENTS AND METHODS: The endoscopic retrograde cholangiopancreatography (ERCP) database was queried for patients with successful double-duct sphincter of Oddi manometry (SOM) who underwent BES alone or PBR between 1994 and 1997. The endoscopist had decided on the technique to be used. From 1995 to 1997 there was a general trend to do PBR. Pancreatitis was defined according to established criteria. RESULTS: The post-ERCP pancreatitis rate among all 436 SOD patients was 19.7%, while 256 patients with normal SOM results had a pancreatitis rate of 12.9%. The use of combined PBR was associated with a lower frequency of pancreatitis compared with BES alone (needle-knife over pancreatic duct stent, 14/131 patients, 10.7 %; pull-type pancreaticobiliary sphincterotomy plus pancreatic stent, 15/78 patients, 19.2%; BES alone, 52/184 patients, 28.3%). Episodes of moderate and severe pancreatitis were seen more frequently in the BES group. CONCLUSION: In SOD patients, post-ERCP pancreatitis rates remain high, but have improved with the addition of combined pancreaticobiliary sphincter therapy.

Impact of pancreatic head resection on direct medical costs in patients with chronic pancreatitis.

OBJECTIVE: To quantitate disease-specific hospital-based medical costs in 34 patients with chronic pancreatitis before and after treatment by either duodenal-preserving pancreatic head resection (DPPHR) or pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Pancreatic head resection in selected patients with chronic pancreatitis provides pain relief and improves quality of life, but the effect on healthcare costs is unknown. METHODS: This observational cohort study comprised 34 selected patients with chronic pancreatitis followed up exclusively at the authors' institution treated by either DPPHR or PPPD between 1992 and 1997. RESULTS: Twenty-one patients had DPPHR and 13 had PPPD. Patients in the PPPD group were slightly older, but other clinical characteristics were similar. Before surgery, the mean number of admissions per patient per year, days in the hospital per patient per year, and disease-specific hospital-based medical costs per patient per year were not significantly different between groups. After surgery, those three variables were similar between the groups but significantly less than preoperative values. Pain control remained significantly improved after 36 months of follow-up. CONCLUSIONS: In selected patients with chronic pancreatitis, DPPHR and PPPD are equally effective in providing long-term pain relief and decreasing disease-specific hospital-based costs.

Roux-en-Y internal drainage is the best surgical option to treat patients with disconnected duct syndrome after severe acute pancreatitis.

BACKGROUND: Roux-en-Y (RNY) internal drainage has been our primary surgical strategy to definitively treat disconnected duct syndrome in patients after severe acute pancreatitis (SAP). This study compares the results of internal drainage with the results of distal pancreatectomy-splenectomy (DPS) performed in a contemporaneous group of patients. METHODS: For 5 years (June 1995 to June 2000), 27 consecutive patients with disconnected duct syndrome after SAP were identified: 13 treated with internal drainage and 14 with DPS. Fistula characteristics, operative management, and clinical outcome were analyzed. Comparisons between groups were made with the Student t test and Fisher exact test, with statistical significance defined as P <.05. RESULTS: Age, sex, etiology of pancreatitis, comorbid diseases, and prior operations were similar between groups. Internal drainage required less operative time (211 +/- 37 vs 269 +/- 88 minutes, P =.04), blood loss (735 +/- 706 vs 2757 +/- 3062 mL, P =.03), and transfusion requirements (0.69 +/- 1.7 vs 4.21 +/- 8.0 units, P =.05). Clinical outcomes--as measured by postoperative complication rate, reoperation rate, fistula recurrence rate, and death rate--were similar between groups. CONCLUSIONS: RNY internal drainage, when technically feasible, is the best surgical option to treat disconnected duct syndrome after SAP.

Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis.

BACKGROUND: Endoscopic measures such as balloon dilation can relieve obstruction and improve symptoms in patients with primary sclerosing cholangitis (PSC). However, the influence of repeated endoscopy to maintain biliary patency on the survival of patients with PSC is unclear. METHODS: This study evaluated the impact of endoscopic therapy on the survival of consecutive patients with PSC undergoing endoscopic therapy. During a 6-year period 63 patients underwent endoscopic therapy. After initial therapy, patients were followed for a median of 34 months. Endoscopic therapy primarily consisted of repeated balloon dilation of dominant biliary strictures. The observed survival of this cohort was estimated (Kaplan-Meier). The predicted survival of the cohort was estimated by using the Mayo Clinic survival model based on clinical information obtained within 3 months before first endoscopic therapy. The Mayo Risk Score was calculated by using the equation R = (0.03 Age, years) + (0.54 log(e) Bilirubin mg/dL) + (0.54 log(e) Aspartate aminotransferase U/mL) + (1.24 Bleed history) - (0.84 Albumin gm/dL). RESULTS: The observed survival over 5 years was significantly higher than the predicted 5-year survival (83% vs. 65%, respectively; p = 0.027). CONCLUSION: These data suggest that repeated endoscopic attempts to maintain biliary patency may improve the survival of patients with PSC and dominant strictures.

Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial.

BACKGROUND: A totally transoral outpatient procedure for the treatment of GERD would be appealing. METHODS: A multicenter trial was initiated that included 64 patients with GERD treated with an endoscopic suturing device. Inclusion criteria were 3 or more heartburn episodes per week while not taking medication, dependency on antisecretory medicine, and documented acid reflux by pH monitoring. Exclusion criteria were dysphagia, grade 3 or 4 esophagitis, obesity, and hiatus hernia greater than 2 cm in length. Patients underwent manometry, endoscopy, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patients were randomized to a linear or circumferential plication configuration. Adverse procedural events were recorded. RESULTS: Mean 6-month symptom score changes demonstrated procedural efficacy. Heartburn severity and frequency as well as regurgitation all improved (p > 0.0001 for each). Twenty-four-hour pH monitoring showed improvement in number of episodes below pH of 4 at 3 and 6 months (p < 0.0007 and 0.0002) and percentage of total time the pH was less than 4 at 6 months (p < 0.011). Plication configuration did not affect symptoms or pH monitoring results. One patient had a self-contained suture perforation that was successfully treated with antibiotics. CONCLUSION: Endoscopic gastroplasty is safe. It is associated with reduced symptoms and medication use at 6 month follow-up in patients with uncomplicated GERD.

Therapeutic biliary endoscopy.

Therapeutic biliary endoscopy is continuing to evolve; some small but important developments were seen during the last year. Competing techniques are continuing to develop.

Influence of cholangiography on biliary sphincter of Oddi manometric parameters.

BACKGROUND: When sphincter of Oddi manometry (SOM) and endoscopic retrograde cholangiopancreatography are performed at the same session, SOM is usually performed immediately before ductography because of concern about the accuracy of the manometric recording after contrast medium injection. However, it would be preferable to inject contrast medium first to identify other causes for a patient's symptoms, allowing selective use of SOM. The aim of this study was to evaluate the effect of cholangiography on sphincter of Oddi (SO) basal pressure. METHODS: Twenty-five patients with suspected SO dysfunction were prospectively studied. Conventional station pull-through manometry of the biliary part of the sphincter was performed before and after cholangiography. The intraductal pressure and basal sphincter pressure were evaluated. RESULTS: The mean intraductal pressure was 8+/-5.5 mm Hg before and 13.3+/-6.8 mm Hg after contrast medium injection (p< 0.01). However, the basal sphincter pressure was not significantly altered (52.9+/-42.1 mm Hg vs. 55.1+/-38.1 mm Hg, p = 0.52). Concordance (normal vs. abnormal) between the basal sphincter pressure before and after ductography was seen in 24 of 25 patients (96%). CONCLUSIONS: Intraductal installation of contrast medium immediately before SOM infrequently alters SO basal pressure in a clinically significant manner. We therefore believe that this sequence can be utilized in clinical practice.

Success of ERCP at a referral center after a previously unsuccessful attempt.

BACKGROUND: The diagnostic and therapeutic success of endoscopic retrograde cholangiopancreatography (ERCP) depends on a number of factors. When an attempt at ERCP fails, the physician must decide whether to repeat the procedure, rely on another imaging procedure (noninvasive or invasive), or refer to another endoscopist/center. Our aim in this prospective study was to determine the role of a second attempt at ERCP at a referral ERCP center. METHODS: Five hundred sixty-two patients were referred for ERCP after having undergone a previous unsuccessful attempt to visualize the clinically relevant duct(s). RESULTS: The overall success in visualizing the desired duct was 96.4% (542 of 562). Advanced techniques for cannulation were used in 41% (229 of 562). Anatomic abnormalities possibly contributing to the previous lack of success were present in 27% of cases. ERCP with or without manometry identified a cause or potential cause for the signs and symptoms in 86% of patients. Sixty complications occurred in 57 patients (10.1%). ERCP was unsuccessful in 20 patients (3.6%). CONCLUSIONS: The cannulation success rate and diagnostic yield of further ERCP with an acceptable complication rate warrant consideration of referral to centers with available resources and expertise.