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Background: Cholesterol, in the form of bile salts, is reabsorbed from the small intestine via the enterohepatic circulation. Biliary sphincterotomy increases the delivery of bile to the terminal ileum. If the absorptive capacity is exceeded, cholesterol excretion may increase, resulting in a decrease in serum cholesterol levels and improvement in serum lipid profiles., Aim: To determine the effect of biliary sphincterotomy on serum cholesterol levels in patients without biliary obstruction., Patients and Methods: Postcholecystectomy patients with type III biliary sphincter of Oddi dysfunction (disabling pancreatobiliary-type pain with normal liver function tests and bile duct diameter) who underwent biliary sphincterotomy were identified retrospectively from the endoscopic retrograde cholangiopancreatography database. Baseline (pre-endoscopic retrograde cholangiopancreatography) laboratory investigations (including cholesterol) were obtained for all patients. The effect of sphincterotomy on total cholesterol levels was noted in all patients who returned for subsequent procedures (temporary pancreatic stent removal or evaluation of recurrent symptoms), and also in the subgroup of patients with baseline hypercholesterolemia (higher than 5.18 mmol/L)., Results: In the present pilot study, the performance of biliary sphincterotomy was associated with a reduction in total serum cholesterol levels in postcholecystectomy patients without biliary obstruction. This was statistically significant in patients with a baseline cholesterol level higher than 5.18 mmol/L. A possible effect on low- and high-density lipoprotein concentrations was not evaluated. The influence of dietary changes and exercise were not accounted for., Conclusion: A prospective, controlled study involving a larger series of patients is required to determine whether biliary sphincterotomy lowers cholesterol levels and improves lipid profiles.

Background: Accurate nonoperative diagnosis of proximal biliary strictures (PBSs) is often difficult., Objective: To report our experience with EUS-guided FNA (EUS-FNA) of PBSs following negative or unsuccessful results with brush cytology during ERCP., Design: Retrospective cohort study., Setting: Single, tertiary referral hospital in Indianapolis, Indiana., Patients: Consecutive subjects from January 2001 to November 2004 who underwent EUS-FNA of a PBS documented by ERCP., Interventions: EUS-FNA of PBS., Main Outcome Measures: Performance of EUS-FNA, with the final diagnosis determined by surgical pathology study or the results of EUS-FNA and follow-up., Results: A total of 291 biliary strictures undergoing EUS were identified. Of these, 26 (9%) had PBSs and 2 were excluded. EUS-FNA was not attempted in 1 because no mass was visualized. The second had a PBS seen on magnetic resonance cholangiopancreatography, but no ERCP was performed. Twenty-four patients (14 men; mean age, 68 years) underwent EUS-FNA of a PBS following ERCP brush cytology studies that were either negative/nondiagnostic (20) or unable to be performed (4). EUS visualized a mass in 23 (96%) patients, including 13 in whom previous imaging detected no lesion. EUS-FNA (median, 4 passes; range, 1-11) demonstrated malignancy in 17 of 24 (71%) patients with findings showing adenocarcinoma (15), lymphoma (2), atypical cytology (3), or benign cells (4). No complications were noted. Pathology results from 8 of 24 (33%) patients who underwent surgery showed hilar cholangiocarcinoma (6), gallbladder cancer (1), and a benign, inflammatory stricture (1). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 77% (95% confidence interval [CI], 54%-92%), 100% (95% CI, 15%-100%), 100% (95% CI, 83%-100%), 29% (95% CI, 4%-71%), and 79% (95% CI, 58%-93%), respectively., Limitations: Histopathologic correlation of EUS-FNA findings was limited to 8 of 24 (33%) patients who underwent surgery., Conclusions: EUS-FNA is a sensitive method for the diagnosis of PBSs following negative results or unsuccessful ERCP brush cytology. The low negative predictive value does not permit reliable exclusion of malignancy following a negative biopsy.

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.

Background: Droperidol is a known effective adjunctive agent for sedation/analgesia during endoscopic procedures, particularly in patients who are difficult to sedate with narcotics and benzodiazepines alone. However, the Food and Drug Administration (FDA) warning about potential droperidol-related fatal cardiac arrhythmias, issued in December 2001, led to concern about its safety in current clinical practice., Objective: In this study, we evaluated the effects of droperidol on the Bazett's corrected QT interval (QTcB) administered to patients undergoing ERCP and frequency of cardiac arrhythmias., Design: We retrospectively reviewed the medical records of patients who, at our institute, underwent ERCP while under sedation/analgesia and who received droperidol. Our protocol for patients who are considered to be candidates for droperidol use includes obtaining an ECG before and 1 to 3 hours after the procedure., Results: From April 2002 to October 2004, 6292 ERCPs were performed, of which 3113 patients with normal baseline QTcB (2001 women, 1112 men) received droperidol. Mean dosages were 4.3 mg (range, 1.25-10 mg) in women and 4.5 mg (range, 1.25-13.75 mg) in men. A total of 233 patients (7.48%; 133 women, 100 men) developed QTcB prolongation. Mean increases of the QTcB above the upper limit of normal were 16 milliseconds in women (range, 1-194 milliseconds) and 22 milliseconds in men (range, 1-310 milliseconds). Of these, 15 patients (0.48%; 8 women, 7 men) had marked prolongation of the QTcB (defined QTcB, >500 milliseconds). No serious dysrhythmias occurred., Conclusions: Droperidol at usual doses during sedation/analgesia may precipitate QTcB prolongation above the normal range. However, no QT-related arrhythmias were noted in this study. Clinically significant cardiac events are probably rare with droperidol, despite documented QTcB effects. Baseline electrocardiogram for excluding patients with prolonged baseline QTcB and 1 to 3 hours afterward monitoring appears adequate when using droperidol. The study is still too small to detect very infrequent arrhythmia events.

Background: Hepatic arterial infusion of fluoropyrimidines has been widely used for the treatment of hepatic metastasis from colorectal cancer. One major complication of such treatment is biliary sclerosis resembling primary sclerosing cholangitis, which has an incidence ranging from 8% to 26%., Aim: We evaluated the efficacy and long-term outcome of endoscopic therapy in the management of chemotherapy-induced sclerosing cholangitis (CISC)., Methods: With the use of an endoscopic retrograde cholangiopancreatography (ERCP) database, all patients with a diagnosis of CISC who had endoscopic therapy between March 1995 and March 2005 were identified. The indications, findings, therapies, and complications for all patients undergoing ERCP were recorded in this database. Additional information was obtained by review of medical records., Results: Eleven patients (six men and five women) were identified. The mean age at presentation was 59.5 years (range, 36-76 years). Cholangiogram findings revealed stricture confined to the common hepatic duct in two patients, involving the hilum in seven patients, involving the right and/or left main hepatic ducts in nine patients, and extending to the intrahepatic radicals in two patients. All patients had successful endoscopic therapy to alleviate the presenting symptom. The grade and extent of biliary strictures did not change in five patients, improved in one patient, recurred in two patients, and progressed in two patients over the follow-up period of 28.2 months (range, 4-60 months)., Conclusion: Although long-term follow-up of patients with CISC is limited by the dismal prognosis of the underlying malignancy, CISC has a recalcitrant pattern that rarely improves with endoscopic therapy. However, endoscopic therapy seems to be an effective method of palliation.

Bile duct stones are routinely removed at time of endoscopic retrograde cholangiopancreatography (ERCP) after biliary sphincterotomy with standard balloon or basket extraction techniques. However, in approximately 10% to 15% of patients, bile duct stones may be difficult to remove due to challenging access to the bile duct (periampullary diverticulum, Billroth II anatomy, Roux-en-Y gastrojejunostomy), large (> 15 mm in diameter) bile duct stones, intrahepatic stones, or impacted stones in the bile duct or cystic duct. The initial approach to the removal of the difficult bile duct stone is to ensure adequate biliary sphincter orifice diameter with extension of biliary sphincterotomy or balloon dilation of the orifice. Mechanical lithotripsy is a readily available adjunct to standard stone extraction techniques and should be available in all ERCP units. If stone extraction fails with these maneuvers, two or more bile duct stents should be inserted, and ursodiol added to aid in duct decompression, stone fragmentation, and stone dissolution. Follow-up ERCP attempts to remove the difficult bile duct stones may be performed locally if expertise is available or alternatively referred to a tertiary center for advanced extracorporeal or intracorporeal fragmentation (mother-baby laser or electrohydraulic lithotripsy) techniques. Nearly all patients with bile duct stones can be treated endoscopically if advanced techniques are utilized. For the rare patient who fails despite these efforts, surgical bile duct exploration, percutaneous approach to the bile duct, or long-term bile duct stenting should be discussed with the patient and family to identify the most appropriate therapeutic option. A thoughtful approach to each patient with difficult bile duct stones and a healthy awareness of the operator/endoscopy unit limitations is necessary to ensure the best patient outcomes. Consultation with a dedicated tertiary ERCP specialty center may be necessary.

Background: Cancer detection rates with biliary brush sampling remain disappointingly low. A low cellular yield is often the limiting factor in making a diagnosis of malignancy. The new Cytolong brush (Cook Endoscopy, Winston-Salem, NC) is 3 mm in diameter, 5 cm long, with stiffer bristles oriented at 45 degrees on a 7F sheath. We hypothesized that this new brush might improve cancer detection rates by increasing cellular yield., Methods: Patients found to have a biliary stricture suspicious for neoplasia on ERCP were randomized to undergo brush sampling for cytology with a standard Geenen brush (GB; Cook Endoscopy, Winston-Salem, NC) [3 mm in diameter, 1.5 cm long, bristles oriented at 90 degrees on a 6F sheath] or the Cytolong brush (CB). Repeat sampling was then performed with the other brush. Stricture dilation was not performed prior to brushing. Specimen results were considered normal, atypical (considered benign), highly atypical (suspicious for cancer), or malignant. All specimens were assigned a cellularity score (0 to 3, insufficient to excellent). Final diagnosis was based on cytologic results plus surgery, EUS, autopsy, or clinical follow-up., Results: From November 2001 to July 2003, 102 patients had specimens obtained from 94 malignancies (47% pancreatic cancer). The cancer detection rate was 25 of 94 (27%) using CB and 28 of 94 (30%) with GB (p = NS). No patient had positive cytology results with CB and negative cytology results with GB. The yield of the two brushes combined was 28 of 94 (30%). Cancer detection rates of 28% (18 of 64) and 31% (20 of 64) were found for CB and GB, respectively, in distal biliary strictures, and 23% (7 of 30) and 27% (8 of 30) in proximal strictures (p = NS). Insufficient or limited cellularity was seen less frequently with CB (11 of 98) than with GB (17 of 98), and the mean cellular yield was greater with CB than GB (2.6 vs 2.4, p = 0.006)., Summary: Despite improved cellularity, cancer detection rates were not improved by using the larger Cytolong brush in this study. There was no statistical difference between the brushes in both proximal and distal biliary strictures., Conclusions: The yield of biliary brush cytology at ERCP remains low. Increasing brush size and bristle stiffness does not increase detection rates. Newer devices and processing techniques are required to allow detection rates to approach those attained in other GI tract malignancies.

Objectives: Our goal is to evaluate the indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children., Methods: Our database was searched for patients 17 years of age or younger undergoing ERCP between January 1994 and March 2003. Additional information was obtained by chart review. The safety and technical success of ERCP were examined. Complications were classified by the consensus criteria., Results: A total of 245 patients (95 M, 150 F; mean age 12.3 years) underwent 329 examinations. Indications included biliary pathology (n = 93), pancreatic pathology (n = 111), and chronic abdominal pain of suspected biliary or pancreatic origin (n = 41). The ERCP findings were bile duct stone(s) (n = 29), benign biliary stricture (n = 19), primary sclerosing cholangitis (n = 7), anomalous pancreaticobiliary union (n = 8), choledochal cyst (n = 5), bile duct leak (n = 6), malignant biliary stricture (n = 2), biliary atresia (n = 1), chronic pancreatitis (n = 44), pancreas divisum (n = 26), pancreatic duct stricture with (n = 6) or without (n = 9) leak, pancreatic tumor (n = 1), periampullary adenoma (n = 2), and sphincter of Oddi dysfunction (n = 65). Endoscopic therapies were performed in 71% of the procedures and included sphincterotomy, stone extraction, stricture dilation, endoprosthesis placement, snare papillectomy, and cystoduodenostomy. Thirty-two (9.7%) post-ERCP complications occurred and included cholangitis in 1 patient and pancreatitis in 31. The pancreatitis was graded mild in 24, moderate in 5, and severe in 2. No mortality related to ERCP occurred., Conclusions: Diagnostic and therapeutic ERCP results are similar in children and adults except for a lower incidence of malignant disease in children. Technical success rates are high. However, ERCP-related pancreatitis is not uncommon, and the risk and benefits should be carefully reviewed before proceeding. Outcome data are necessary and is currently being accumulated at our institution.

Background: The diagnosis of early chronic pancreatitis (CP) is difficult, and the role of EUS-FNA cytology for this indication remains unclear. The aim of this study is to determine the utility and the safety profile of EUS-guided Trucut biopsy (EUS-TCB) for the histologic diagnosis of suspected nonfocal CP., Methods: After radial EUS, patients with suspected CP (> or =3 EUS criteria) underwent attempted transgastric EUS-TCB of the pancreas. Histopathologic specimens were examined by one pathologist and were classified as nondiagnostic, normal pancreas, and probable or definite CP. Within 1 week after EUS, ERCP was performed by an endoscopist blinded to the EUS results. The severity of CP by ERCP was stratified by the Cambridge classification. Agreement between tests for the diagnosis of CP was evaluated by a kappa statistic., Results: Of 45 patients screened, 15 declined and 30 (12 men and 18 women, mean age 44 years) underwent diagnostic EUS. Of these, 18 (60%) had suspected CP and 16 underwent attempted biopsy. Calcific pancreatitis in two patients precluded EUS-TCB. EUS-TCB results were as follows: probable CP (1), normal pancreas (8), nondiagnostic (6), device malfunction (1). Complications after EUS-TCB occurred in two patients with normal pancreatic biopsies were the following: acute pancreatitis (1) and abdominal pain without pancreatitis (1), both of whom were hospitalized and discharged within 23 hours. Six patients refused ERCP and two (per protocol) did not undergo ERCP. For the remaining 22, agreement between diagnostic EUS and ERCP was moderate (kappa, 0.40). Agreement between EUS and ERCP with EUS-TCB were poor (kappa, 0) and fair (kappa, 0.25), respectively., Conclusions: Transgastric EUS-TCB of suspected nonfocal CP infrequently demonstrates histologic CP in clinically suspected disease. Because of potential complications and limited diagnostic yield, this technique is not currently recommended for evaluation of these patients.

Pancreas divisum (PD), the most common congenital variant of pancreatic duct anatomy, occurs when the ductal systems of the ventral and dorsal pancreatic ducts fail to fuse during the second month of gestation. With non-union of the ducts, the major portion of the pancreatic exocrine secretion enters the duodenum by way of the dorsal duct and minor papilla. It has been generally accepted that a relative obstruction to pancreatic exocrine secretory flow through the minor duct and minor papilla could result in pancreatitis in small numbers of patients with PD. The debate whether PD causes pancreatitis continues, although most authorities agree that PD is a definite cause in a subgroup of patients. Most patients with PD and well-documented acute recurrent pancreatitis have responded favorably to surgical sphincteroplasty of the minor papilla. Endoscopic retrograde cholangiopancreatography (ERCP) is the most common procedure for diagnosis PD in patients who have pancreatobiliary symptoms. MRCP is being increasingly used to establish the diagnosis and secretin stimulation can improve ductal images greatly. Endoscopic management of symptomatic patients with PD is evolving. Only a limited number of series are available, using endoscopic pancreatic stent placement, minor papilla endoscopic papillotomy, or both to decompress the dorsal duct in an effort to restore pancreatic exocrine secretory flow. Even with relatively small numbers of patients and a near absence of controlled, randomized trials, it appears that the patients most likely to benefit, as with surgery, are those with well-documented ARP rather than pain alone or chronic pancreatitis. Overall we recommend that pancreatic stenting and pancreatic sphincterotomy should be done only in large centers with experience in therapeutic ERCP. Further randomized trials would be of interest.

Background: Metastatic lesions of the pancreas are a rare but important cause of focal pancreatic lesions. The purpose of this study is to describe the EUS features, cytologic diagnoses, and clinical impact of a cohort of patients with pancreatic metastases diagnosed by EUS-guided FNA (EUS-FNA)., Methods: Over a 6-year period, in a retrospective, multicenter study, patients had the diagnosis of pancreatic metastases confirmed with EUS-FNA. All examinations were performed by one of 5 experienced endosonographers. The EUS and the clinical findings of pancreatic metastases were compared with those of a cohort with primary pancreatic malignancy., Results: Thirty-seven patients with possible metastases were identified, and 13 were excluded because of diagnostic uncertainty. The remaining 24 underwent EUS-FNA (mean passes 4.1) of a pancreatic mass without complications. Diagnoses included metastases from primary kidney (10), skin (6), lung (4), colon (2), liver (1), and stomach (1) cancer. In 4 (17%), 16 (67%), and 24 (100%) patients, EUS-FNA provided the initial diagnosis of malignancy, tumor recurrence, and pancreatic metastases, respectively. Four (17%) metastases initially were discovered by EUS after negative (n = 3) or inconclusive (n = 1) CT scans. Compared with primary cancer, pancreatic metastases were more likely to have well-defined margins (46% vs. 4%) compared with irregular (94% vs. 54%; p < 0.0001) margins. No statistically significant difference between the two populations was noted for tumor size, echogenicity, consistency, location, lesion number, or number of FNA passes performed., Conclusions: Pancreatic metastases are an important cause of focal pancreatic lesions and may occasionally be discovered during EUS examination after previously negative or inconclusive CT. Use of immunocytochemistry, when available, may help to confirm a suspected diagnosis. These lesions are more likely to have well-defined EUS margins compared with primary pancreatic cancer.

Background: Accurate preoperative detection and staging of pancreatic cancer may identify patients with locoregional disease that is amenable to surgical resection., Objective: To compare endoscopic ultrasonography and multidetector computed tomography (CT) for the detection, staging, and resectability of known or suspected locoregional pancreatic cancer., Design: Prospective, observational, cohort study., Setting: Single, tertiary referral hospital in Indianapolis, Indiana., Patients: 120 participants with known or suspected locoregional pancreatic cancer., Interventions: Endoscopic ultrasonography followed by multidetector CT was performed in all patients. Patients with known or suspected pancreatic cancer deemed potentially resectable by 1 or both tests were considered for surgery., Measurements: Detection, staging, and resectability of pancreatic cancer. Surgically resected pancreatic cancer with negative microscopic histologic margins was considered resectable., Results: Of 120 patients enrolled, 104 (87%) underwent endoscopic ultrasonography and CT. Of the 80 patients with pancreatic cancer, 27 (34%) were managed nonoperatively, and 53 (66%) treated surgically had resectable (n = 25) or unresectable (n = 28) cancer. For the 80 patients with cancer, the sensitivity of endoscopic ultrasonography (98% [95% CI, 91% to 100%]) for detecting a pancreatic mass was greater than that of CT (86% [CI, 77% to 93%]; P = 0.012). For the 53 surgical patients, endoscopic ultrasonography was superior to CT for tumor staging accuracy (67% vs. 41%; P < 0.001) but equivalent for nodal staging accuracy (44% vs. 47%; P > 0.2). Of the 25 resectable pancreatic tumors in patients recommended for surgery, endoscopic ultrasonography and CT correctly identified 88% and 92%, respectively, as resectable. Of the 28 unresectable pancreatic tumors in patients recommended for surgery, endoscopic ultrasonography and CT correctly identified 68% and 64%, respectively, as unresectable., Limitations: Radiologists who read the scans and endosonographers were not blinded to previous radiographic information. Because of the modest sample size, CIs of the sensitivity estimates were sometimes wide., Conclusion: Compared with multidetector CT, endoscopic ultrasonography is superior for tumor detection and staging but similar for nodal staging and resectability of preoperatively suspected nonmetastatic pancreatic cancer.

Background: Tumors of the major and the minor duodenal papillae can be malignant or premalignant, and traditionally are treated by surgical excision. This study evaluated the safety and the outcome of endoscopic snare resection of such tumors., Methods: All patients with tumors of the major or the minor papilla treated by endoscopic snare resection over a 10-year period (1994-2003) were identified from an ERCP database. Patients with tumors that had endoscopic features of malignancy and those proven to be cancerous by biopsy were excluded. Papillectomy was performed by electrosurgical snare resection. A pancreatic stent usually was placed before or after excision. Residual tumor was eradicated by repeated procedures. Endoscopic surveillance was at the discretion of the endoscopist., Results: Seventy snare resections were performed in 55 patients (mean age 59 years). Histopathologic diagnoses were the following: adenoma (45 patients; 7 with focal high-grade dysplasia, 6 with intraductal extension), adenocarcinoma (5), carcinoid tumor (2), gastric heterotopia (1), and normal histology (2). Fourteen patients had familial adenomatous polyposis. Of the 39 patients with isolated extraductal adenoma per cholangiogram, two underwent surgical resection because of persistent high-grade dysplasia, and 37 were successfully treated by endoscopic papillectomy alone. During follow-up (mean 30 months), 18 of 37 patients (49%) had no recurrence, 7 had recurrent adenoma (mean time interval to recurrence 27 months), two died of unrelated illnesses, and 10 are awaiting follow-up. Of the 6 patients with intraductal adenoma per cholangiogram, two underwent surgical resection, two had intraductal photodynamic therapy, and two had endoscopic snare resection. Intraductal tumor in the 4 latter patients was eliminated, although it recurred in one of the patients who had photodynamic therapy. Of the 7 patients with adenocarcinoma or carcinoid tumor, pancreaticoduodenectomy was performed in 3 and palliative papillectomy was performed in 4 unsuitable for surgery. One patient with carcinoid tumor of the minor papilla is alive, without recurrence, at 5 years after papillectomy. There were 10 procedure-related complications (14.5%), including pancreatitis (5), bleeding (4), and mild perforation (1). There was no procedure-related death., Conclusions: Most adenomas of the duodenal papillae without intraductal extension can be fully resected by snare papillectomy. However, adenoma recurs in about a third of patients. Endoscopic therapy appears to be a reasonable alternative to surgery for management of papillary tumors. Longer follow-up is needed to determine the true recurrence rate and if endoscopic re-treatments are effective.

Pancreaticoduodenectomy is often avoided in patients with portal or superior mesenteric venous involvement due to the perception that venous resection is complex, morbid, and carries a poor long-term survival. Our recent experience using state-of-the-art imaging and strict resection criteria show that venous reconstruction increases operative time, transfusion requirements, intensive care unit stay, and total hospital length of stay, but has no significant impact on operative morbidity rates, mortality rates, or the incidence of positive histologic margins. Kalpan-Meier life table analysis shows similar survival curves when compared to a contemporary cohort of patients who do not undergo venous reconstruction.

Objectives: The aim of this study was to report the sensitivity, cytological diagnoses, endoscopic ultrasound (EUS) features, complications, clinical impact, and long term follow-up of a large single-center experience with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of benign and malignant solid liver lesions., Methods: A database of cytologic specimens from EUS-FNA was reviewed to identify all hepatic lesions aspirated between January, 1997, and July, 2002. Procedural indications, prior radiographic data, patient demographics, EUS examination results, complications, and follow-up data were obtained and recorded., Results: EUS-FNA of 77 liver lesions in 77 patients was performed without complications. Of these 77 lesions, 45 (58%) were diagnostic for malignancy, 25 (33%) were benign, and seven (9%) were nondiagnostic. A total of 22 lesions were confirmed as negative for malignancy by follow-up (mean 762 days, range 512-1556 days) or intraoperative examination; however, seven lesions could not be classified as benign or malignant. Depending on the status of the seven unclassified lesions, sensitivity of EUS-FNA for the diagnosis of malignancy ranged from 82 to 94%. When compared with benign lesions, EUS features predictive of malignant hepatic masses were the presence of regular outer margins (60% vs 27%; p = 0.02) and the detection of two or more lesions (38% vs 9%; p = 0.03). Of the 42 patients with malignancy identified by EUS-FNA and other available imaging records, EUS detected the malignancy in 41% of patients with previously negative examinations. For the 45 subjects with cytology positive for malignancy, EUS-FNA changed management in 86% of subjects., Conclusion: EUS-FNA of the liver is a safe and sensitive procedure that can have a significant impact on patient management. Prospective studies comparing the accuracy and complication rate of EUS-FNA and percutaneous fine needle aspiration (P-FNA) for the diagnosis of liver tumors are needed.

Hypothesis: Malignant intraductal papillary mucinous neoplasms (IPMNs) can be predicted before surgery., Design: Retrospective review of a prospectively collected database., Setting: Academic, urban, tertiary care hospital., Patients: Sixty-four consecutive patients with a pathological diagnosis of IPMN., Interventions: All 64 patients underwent surgical intervention for IPMN between December 8, 1988, and October 16, 2002., Main Outcome Measures: Reliable predictors of malignancy., Results: The 64 patients underwent 69 operations: 39 pancreaticoduodenectomies, 18 distal pancreatectomies, 7 total pancreatectomies, 4 neck and/or body pancreatectomies, and 1 cystgastrostomy with pancreatic biopsy. Twenty-three of 69 specimens were malignant-12 in situ (high-grade dysplasia) and 11 invasive. In a univariate analysis of 12 clinical signs or symptoms recorded, diabetes mellitus and jaundice showed a significant association with malignancy of IPMN. Of 24 serum chemistry studies, hematologic studies, and tumor marker analyses (in serum, bile, and pancreatic fluid), elevation of serum alkaline phosphatase and glucose levels showed correlation with malignancy. Computed tomography, ultrasound, and endoscopic retrograde cholangiopancreatography findings did not distinguish between benign and malignant tumors. Atypia on preoperative cytologic analysis was specific for malignancy (93%) but lacked the same degree of sensitivity (40% in situ, 91% invasive, and 67% overall)., Conclusions: Malignancy of IPMNs is suggested by new-onset diabetes mellitus, jaundice, and elevations in serum glucose or alkaline phosphatase levels. Atypia on preoperative cytologic testing is the finding most predictive of malignancy. The absence of these features does not predict benign disease. These findings may help guide patient and physician decision making.

As a first step toward elucidating the in vivo function of plant bZIP proteins and their related G-box cis elements, we have introduced a dominant negative inhibitor of G-box-dependent transcriptional activation into tobacco plants by transforming them with a truncated EmBP-1 gene (deltaEmBP) containing the DNA binding and dimerization domains under the control of the CaMV 35S promoter. Five independent lines of transgenic plants expressing deltaEmBP were identified, as demonstrated by immunodetection of the transgenic protein in leaf extracts, and the ability of the protein to bind a target G-box DNA sequence. The transgenic plants exhibited an abnormal phenotype characterized by interveinal chlorosis, growth inhibition and weakening of stems and petioles, the severity of which positively correlated with deltaEmBP expression and G-box DNA binding capability. Furthermore, development of chlorosis and growth inhibition was dependent on growth irradiance. Low light promoted the development of interveinal chlorosis and growth inhibition in the transgenic plants, whereas high light conditions led to near-complete amelioration of the abnormal phenotype. Transgenic plants under both light regimes showed signs of impaired stem and petiole function which was not observed in wild-type tobacco. RhcS gene expression was not significantly altered by deltaEmBP expression, suggesting that down-regulation of this gene was not responsible for the altered phenotype. The results suggest that G-box elements specific for the EmBP-1 class of bZIP proteins have an important developmental function in vegetative plant tissues, and that the trans-dominant negative mutant approach is a useful tool for continued in vivo functional analysis of bZIP transcription factors and their corresponding cis elements in plants.

Although jejunal tube placement through a percutaneous endoscopic gastrostomy (PEG) has not been proven to be preferable to PEG feeding, it would be theoretically advantageous for those patients prone to gastrointestinal aspiration. However, reliable placement of a small bowel feeding tube through a PEG has been technically difficult. We have previously reported successful placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal complications. These results are in contrast to other series that report technical difficulty, frequent tube dysfunction and gastric aspiration. We describe an over-the-wire PEG/J technique performed by multiple operators at two medical centers. Gastrostomy tube placement was successful in 94% of patients. Initial placement of the jejunal tube was successful in 88% of patients. Second attempts were 100% successful. The average procedure time was 36 minutes. The distal duodenal and jejunal placement of the jejunal tube resulted in no episodes of gastroduodenal reflux. Complications included jejunal tube migration (6%), clogging (18%), and unintentional removal (11%). The majority of patients were ultimately converted to either oral or intragastric feedings. We conclude that the PEG/J system is a reliable, reproducible method of small bowel feeding and is associated with no episodes of tube feeding reflux when the jejunal tube is positioned in the distal duodenum or beyond. Furthermore, it provides a temporary nutritional bridge for those patients who are later transitioned to either PEG or oral feeding.

The "self-directed team" concept is an innovative approach in the healthcare setting. Long-term benefits of customer satisfaction and quality improvement are consistent with concepts of total quality improvement and patient-focused care. Initial investment of time and money pays off in low turnover and marked employee and patient satisfaction.

Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed agents, especially for elderly patients. These drugs frequently produce mucosal petechiae and erosions in the stomach and duodenum, but these conditions are rarely of clinical significance. NSAIDs, however, cause considerable morbidity and mortality due to their ability to cause gastric and duodenal ulcers. NSAID-induced ulcers are most likely to develop in elderly women receiving multiple NSAIDs for prolonged periods. NSAIDs injure gastric and duodenal mucosa by both a topical and a systemic effect. The latter is responsible for the pathogenesis of NSAID-associated ulcers. These ulcers are particularly prone to perforation and hemorrhage. Both complications frequently occur in asymptomatic long-term users of NSAIDs. H2 antagonists prevent NSAID-related duodenal ulcers but are not effective for prevention of gastric ulcers. Misoprostol is the only agent proven to decrease the risk of gastric ulcers in patients receiving NSAIDs. Both H2 antagonists and omeprazole are highly effective for the treatment of established duodenal ulcers in patients receiving NSAIDs. H2 antagonists also heal gastric ulcers in these patients but at slower rates than in patients not receiving NSAIDs. The existing literature is reviewed, and guidelines for prophylaxis against NSAID-induced ulcers and treatment of established ulcers are provided.

Gastric acid produced by the parietal cells has a significant role in a variety of gastrointestinal diseases, such as duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. We address acid production by the parietal cell and the pharmacological means to control gastric acid secretion. The physiology of parietal cell acid secretion is reviewed. The role of acid-suppressive therapy with histamine H2 antagonists and omeprazole in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease is discussed. Pharmacology, side-effect profile, and dosage requirements of the histamine H2 antagonists and omeprazole are outlined.

The Philadelphia Neurological Society was founded 100 years ago by Charles K. Mills, together with Wharton Sinkler, J.T. Eskridge, and Francis X. Dercum. S. Weir Mitchell was the first president and served for 5 additional years. American neurology was born in Philadelphia at the Orthopedic Hospital and the Infirmary for Nervous Diseases. The growth in neurology in this country is reflected in the activities of the Philadelphia Neurological Society.

32 of 45 (71.1%) patients with carotid artery distribution transient ischemic attacks had normal cranial computerized tomography (CCT). 9 (20%) had cerebral atrophy. Incidental abnormalities were found in 3 (6.6%) patients, while a hypodense lesion corresponding to the site of neurological dysfunction was seen in only 1 (2.2%) patient. The latter showed a persistent abnormality in follow-up studies on the 8th and the 23rd day after the initial event. Our clinical CCT correlation did not demonstrate the frequency of hypodense lesions reported by some authors. Furthermore an increased incidence of cerebral atrophy was found compared to the one reported previously.

Raeder's paratrigeminal syndrome is a disorder manifested by unilateral ptosis, miosis, intact facial sweating, and severe pain in the distribution of the ophthalmic division of the fifth nerve. It is a clinical pattern where, usually, a middle-aged male gets a severe throbbing supraorbital headache accompanied by ptosis and miosis. The headache is intermittently present for several weeks or months. Facial sweating may or may not be affected. This report describes a female with Raeder's syndrome who had unilateral facial anhibrosis.

The authors warn physicians that intoxication by Angel's Trumpet (Datura sauveolens) is becoming more frequent due to its use by adolescents and young adults as a legal, readily available hallucinogen. Ingestion of Angel's Trumpet flowers or a tea brewed from them results in an alkaloid-induced central nervous system anticholinergic syndrome characterized by symptoms such as fever, delirium, hallucinations, agitation, and persistent memory disturbances. Severe intoxication may cause flaccid paralysis, convulsions, and death. Treatment with intravenous physostigmine reverses the toxic effects of Angel's Trumpet.