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.

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.

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 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.

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.

Triple-tissue sampling at ERCP in malignant biliary obstruction.

BACKGROUND: Procurement of cytologic samples by brushing is common practice at endoscopic retrograde cholangiopancreatography (ERCP) but has low sensitivity for cancer detection. Limited data are available on other techniques, including endoluminal fine-needle aspiration and forceps biopsy. This series reviews the yield of these three stricture sampling methods. METHODS: In this prospective study, patients with biliary obstruction with a clinical suspicion of malignancy underwent triple-tissue sampling at one ERCP session. Final cancer diagnosis was based on all sampling methods plus surgery, autopsy, and clinical follow-up. Tissue specimens were reported as normal, atypia, or malignant. RESULTS: A total of 133 patients were evaluated: 104 had cancer and 29 had benign strictures. Tissue sampling sensitivity varied according to the type of cancer; the highest yield was seen in ampullary cancers (62% to 85%). The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 52% if atypia was considered benign and 77% if it was considered malignant. The addition of a second or third technique increased sensitivity rates in most instances. No serious complications occurred from the tissue sampling methods. CONCLUSIONS: Tissue sampling sensitivity varied according to the type of cancer. Combining a second or third method increased sensitivity; general use of at least two sampling methods is therefore recommended.

Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience.

BACKGROUND: Current methods for staging pancreatic cancer can be inaccurate, invasive, and expensive. Endoscopic ultrasound (EUS) is reported to be highly accurate for local staging of gastrointestinal tumors including pancreatic cancer. The aim of this study was to assess the utility of EUS and CT for staging pancreatic cancer by comparing staging accuracies in surgical patients and evaluating the potential impact of EUS staging and training. METHODS: This was a preoperative comparison of the diagnostic operating characteristics of these procedures in a referral-based academic medical center. Data were collected on 151 consecutive patients referred with confirmed pancreatic cancer between April 1990 and November 1996. All patients had preoperative CT and EUS performed for staging. In patients undergoing surgery, the surgical staging and/or findings were used to confirm EUS and CT staging. RESULTS: Eighty-one (60%) of 151 patients underwent surgery and made up the study subset. In these 81 patients, surgical exploration provided a final T staging in 93% (75 of 81), N staging in 88% (71 of 81) and data on vascular invasion in 93% (75 of 81). In the surgical patient group, with surgical correlation, EUS accuracy for T staging was as follows: T1 92%, T2 85%, T3 93%, and for N staging was: N0 72%, and N1 72%. CT accuracy for T staging was as follows: T1 65%, T2 67%, T3 38%, and for N staging was as follows: N0 52% and N1 100%. CT failed to detect a mass in 26% of patients with a confirmed tumor at surgery. Overall accuracy for T and N staging was 85% and 72% for EUS and 30% and 55% for CT, respectively. The ability to accurately predict vascular invasion was 93% for EUS and 62% for CT (p < 0.001). EUS was 93% accurate for predicting local resectability versus 60% for CT (p < 0.001). Last, the data were divided into two groups for the senior endosonographer's experience: procedures performed between 1990 and 1992 (98 cases) and 1993 and 1994 (53 cases). This analysis revealed that 7 of 9 instances of mis-staging (78%) occurred in the earlier group, during the learning phase for EUS. CONCLUSIONS: EUS is more accurate than CT for staging pancreatic malignancies, including predicting vascular invasion and local resectability. EUS staging was significantly better than CT for T1, T2, and T3 tumors. EUS staging accuracy improved after 100 cases, thus suggesting a correlation between the accuracy of EUS staging and the number of procedures performed.

Endoscopic therapy in anomalous pancreatobiliary duct junction.

BACKGROUND: Anomalous pancreaticobiliary duct junction is associated with bile duct strictures, pancreatitis, choledochal cysts, and biliary carcinoma. Limited data are available for outcomes of endoscopic therapy. METHODS: Review of 7537 patients undergoing endoscopic retrograde cholangiopancreatography from 1988 to 1997 yielded 18 patients with anomalous pancreaticobiliary duct junction. Therapeutic responses were tallied by chart review and phone calls. RESULTS: There were 13 women and 5 men, with a mean age of 36 years. Twelve patients had no ductographic evidence of pancreatitis and 6 had chronic pancreatitis. Seven had choledochal cysts. Fifteen patients (83%) underwent endoscopic biliary sphincterotomy, two of whom underwent repeat endoscopic biliary sphincterotomy for recurrence of symptoms. The other therapies included stent placement for benign biliary strictures in 5 patients, lithotripsy of pancreatic stones in 1 patient, and choledochal cyst removal in 4 patients. Three cases with malignant biliary strictures are excluded from endoscopic outcome studies. The 12 patients with pancreatitis had a mean of 2.0 episodes per year before any treatment. After endoscopic therapy 7 patients had no further episodes of pancreatitis, whereas 5 patients had further episodes, with a mean of one additional attack per year, over 3 years mean follow-up. CONCLUSIONS: Patients with anomalous pancreaticobiliary duct junction have complex pathology associated with strictures, choledochal cysts, pancreatitis, and malignancies. Endoscopic therapy appeared to benefit 13 of 15 patients without malignant disease with elimination of or decreased frequency of pancreatitis. Endoscopic therapy appears to be a logical first step in the management of most symptomatic patients with anomalous pancreaticobiliary duct junction.

Classification and management of perforations complicating endoscopic sphincterotomy.

BACKGROUND: The management of perforations after endoscopic sphincterotomy (ES) is controversial. The purpose of this study was to analyze the treatments and outcome of patients with ES perforations. METHODS: Between January 1994 and July 1998, in a series of 6040 endoscopic retrograde cholangiopancreatographies, 2874 (48%) ESs were performed: 40 patients (0.6%) with perforation were identified and retrospectively reviewed. RESULTS: All patients (n = 14) with guidewire perforation (group I) were recognized early, managed medically, and discharged after a mean hospital stay of 3.5 days. Twenty of 22 patients with periampullary perforation (group II) were identified early; 18 patients (90%) had aggressive endoscopic drainage, and none required operation. Of the 2 patients identified late, 1 patient required operation and subsequently died. Mean hospital stay for this group was 8.5 days. Only 1 of 4 patients with duodenal perforations (group III) was identified early; all required operation; 1 patient died, and the mean hospital stay was 19.5 days. CONCLUSIONS: ES perforation has 3 distinct types: guidewire, periampullary, and duodenal. Guidewire perforations are recognized early and resolve with medical treatment. Periampullary perforations diagnosed early respond to aggressive endoscopic drainage and medical treatment. Postsphincterotomy perforations diagnosed late (particularly duodenal) require surgical drainage, which carries a high morbidity and mortality rate.

Pancreatitis and cystic fibrosis gene mutations.

Cystic fibrosis (CF) is a genetic disease with multisystem involvement in which defective chloride transport across membranes causes dehydrated secretions. The protein encoded by the CF gene--the cystic fibrosis transmembrane conductance regulator (CFTR)--functions as a cyclic adenosine monophosphate-regulated chloride channel. The ability to detect CFTR mutations has led to the recognition of its association with a variety of conditions, including chronic bronchitis, sinusitis with nasal polyps, pancreatitis, and, in men, infertility. This article reviews the impact of CF on the pancreas, the role of the CFTR protein in pancreatic secretion, and some of the exciting research identifying mutations in the CFTR gene as a risk factor for idiopathic acute and chronic pancreatitis.

Z-stent for malignant esophageal obstruction.

The Z-stent was one of the first self-expanding metal prostheses used for palliation of malignant esophageal obstruction and respiratory esophageal fistula. Its placement has proved to be effective and relatively safe. This article reviews the evolution of the Z-stent; its multiple designs, placement technique, efficacy, complications, and assets and limitations.