Resistively loaded coplanar waveguide for microwave measurements of induced carriers.

We describe the use of a coplanar waveguide (CPW) whose slots are filled with a resistive film, a resistively loaded CPW (RLCPW), to measure two-dimensional electron systems (2DESs). The RLCPW applied to the sample hosting the 2DES provides a uniform metallic surface serving as a gate to control the areal charge density of the 2DES. As a demonstration of this technique, we present measurements on a Si metal-oxide-semiconductor field-effect transistor and a model that successfully converts microwave transmission coefficients into conductivity of a nearby 2DES capacitively coupled to the RLCPW. We also describe the process of fabricating the highly resistive metal film required for fabrication of the RLCPW.

Proposed thresholds for pancreatic tissue volume for safe intraportal islet autotransplantation after total pancreatectomy.

The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3)/kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3)/kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.

Increased cell migration and plasticity in Nrf2-deficient cancer cell lines.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression is deregulated in many cancers. Genetic and biochemical approaches coupled with functional assays in cultured cells were used to explore the consequences of Nrf2 repression. Nrf2 suppression by Keap1-directed ubiquitylation or the expression of independent short hairpin RNA (shRNA)/siRNA sequences enhanced cellular levels of reactive oxygen species, Smad-dependent tumor cell motility and growth in soft agar. Loss of Nrf2 was accompanied by concomitant Smad linker region/C-terminus phosphorylation, induction of the E-cadherin transcriptional repressor Slug and suppression of the cell-cell adhesion protein E-cadherin. Ectopic expression of the wildtype but not dominant-negative Nrf2 suppressed the activity of a synthetic transforming growth factor-beta1-responsive CAGA-directed luciferase reporter. shRNA knock-down of Nrf2 enhanced the activity of the synthetic CAGA reporter, as well as the expression of the endogenous Smad target gene plasminogen activator inhibitor-1. Finally, we found that Nrf2/Smad3/Smad4 formed an immunoprecipitable nuclear complex. Thus, loss of Nrf2 increased R-Smad phosphorylation and R-Smad signaling, supporting the hypothesis that loss of Nrf2 in an oncogenic context-dependent manner can enhance cellular plasticity and motility, in part by using transforming growth factor-beta/Smad signaling.

Endoscopic ultrasound rendezvous for bile duct access using a transduodenal approach: cumulative experience at a single center. A case series.

Endoscopic ultrasound (EUS)-assisted biliary access is utilized when conventional endoscopic retrograde cholangiopancreatography (ERCP) fails. We report a 10-year experience utilizing a transduodenal EUS rendezvous via a transpapillary route without dilation of the transduodenal tract, followed by immediate ERCP access. Patients included all EUS-guided rendezvous procedures for biliary access that were performed following ERCP failure. EUS-assisted bile duct puncture was performed via a transduodenal approach and a guide wire was advanced through the papilla without any dilation or bougienage of the tract; ERCP was performed immediately afterwards. EUS-assisted biliary rendezvous was attempted in 15 patients (mean age 66 +/- 18.2 years; malignant = 10, benign = 5). Mean diameter of measured bile ducts was 14.3 +/- 5.17 mm (range 4-23 mm). The reasons for initial ERCP failure were tumor infiltration or edema (n = 9), intradiverticular papilla (n = 2), pre-existing duodenal stent (n = 1), and anatomic anomalies (n = 3). Successful EUS-guided bile duct puncture and wire passage were achieved in all 15 patients (100 %), with drainage being successful in 12 / 15 (80 %). Failures occurred in three patients due to inability to traverse the biliary stricture (n = 2) or dissection of a choledochocele with the guide wire (n = 1); all were subsequently drained via percutaneous methods. Stents placed were metallic in eight patients and plastic in four. Complications consisted of moderate pancreatitis after a difficult ERCP attempt in one patient, and bacteremia after percutaneous biliary drainage in another. There were no instances of perforation, extraluminal air or fluid collections. EUS-assisted biliary drainage utilizing a transduodenal rendezvous approach demonstated a high success rate without any complications directly attributable to the EUS access. Advantages over percutaneous biliary and other methods of EUS biliary access include performance under the same anesthesia, and a very small-caliber needle puncture similar to EUS/fine-needle aspiration.

Significant clinical implications of prophylactic pancreatic stent placement in previously normal pancreatic ducts.

Pancreatic duct stent placement is increasingly performed for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP); however stents can result in injury especially in normal ducts. The clinical significance and outcomes of subsequent endoscopic therapy are unknown. This study was a retrospective review of the management of symptomatic stent-induced pancreatic duct injury following stent placement for prevention of post-ERCP pancreatitis in eight patients with previously normal pancreatic ducts. Subsequent treatment included pancreatic sphincterotomy, balloon dilation of stricture, and placement of multiple 3 - 5-Fr soft polymer pancreatic stents. All patients showed improvement or resolution of pancreatic strictures. Five patients had resolution or substantial improvement of pain, one patient showed a fair response with repeated ERCPs, and two patients failed to respond and underwent total pancreatectomy with islet autotransplantation. Pancreatic duct stent-induced ductal injury with significant clinical consequences can occur with conventional polyethylene stents. Endoscopic therapy is moderately effective but some patients develop irreversible damage. Caution should be used when placing standard polyethylene stents in normal ducts. Further research is required to identify safer materials and configurations of pancreatic stents.

Biliary cannulation during endoscopic retrograde cholangiopancreatography: core technique and recent innovations.

Despite advances in imaging and device technology over the past decade, endoscopic retrograde cholangiopancreatography (ERCP) continues to be one of the most technically challenging interventions in endoscopy. The procedure remains compounded by two persistent problems: failure of successful biliary cannulation and post-ERCP pancreatitis (PEP). When performed outside expert high-volume centers, failed biliary cannulation may occur in up to 20 % of cases; repeated and prolonged attempts at cannulation increase the risk of pancreatitis, delay definitive therapy, and necessitate alternative therapeutic techniques with inferior safety profiles . Cannulation technique is believed to be a pivotal factor in the genesis of PEP and is obviously important for successful cannulation. This review will discuss some recent innovations in cannulation technique.

Recent advances and novel methods in pancreatic imaging.

Traditional imaging studies for evaluating pancreatic disease including abdominal ultrasound (US) and computerized tomography (CT) are widely utilized due to their availability, non-invasiveness, and familiarity to practitioners. The addition of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) has contributed significantly to the clinician's the ability to safely sample tissue, stage malignancy, evaluate the pancreatic ductal anatomy, and look for subtle parenchymal changes in the setting of chronic pancreatitis. The role of endoscopic retrograde cholangiopancreatography (ERCP) has diminished with the use of these less invasive modalities. Limitations in these conventional techniques include a lack of sensitivity and specificity in diagnosing early chronic pancreatitis, difficulties in differentiating malignancy from chronic or focal pancreatitis, and accuracy of staging pancreatic malignancy, particularly with regard to vascular involvement. Several recent advances in traditional imaging techniques have been described, which may improve our ability to accurately diagnose and stage pancreatic disease. Advances have been made in the standard modalities for imaging the pancreas such as multidetector CT, micro-bubble contrast enhanced ultrasound, and secretin stimulated MRCP. Other novel methods of pancreatic imaging have recently been described including EUS elastography, optical coherence tomography, diffusion weighted MRI, and MR spectroscopy. This article will review the recent advances in both traditional pancreatic imaging modalities as well as some of the emerging technologies for imaging evaluating diseases of the pancreas. As experience and clinical evidence accumulate, the role of these imaging techniques will continue to evolve.

The role of endoscopic retrograde cholangiopancreatography and endoscopic ultrasound in diagnosis and treatment of acute pancreatitis.

Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for diagnosis and therapy in acute and recurrent pancreatitis. While treatment of biliary disorders leading to pancreatitis is common practice, over the past several years many specialized centers have been directing traditional biliary techniques such as sphincterotomy and stenting towards the pancreas. A justifiable fear of pancreatitis and other complications has caused many endoscopists to shy away from pancreatic endotherapy, but refinements in technique, extensive experience, and most notably the routine use of pancreatic stenting to prevent post-ERCP pancreatitis has opened up the field and allowed for endoscopists in specialized centers around the world to perform diagnostic and therapeutic ERCP of the pancreas safely and effectively. In acute gallstone pancreatitis, the benefit of therapeutic ERCP including biliary sphincterotomy has been proven in randomized controlled trials. There are also data to support the role of ERCP directed at the pancreatic sphincters and ducts in treatment of acute relapsing pancreatitis due to pancreas divisum, sphincter of Oddi dysfunction, smoldering pancreatitis, pancreatic ductal disruptions, and perhaps even in evolving pancreatic necrosis. Many causes of apparently idiopathic pancreatitis can be discovered after an extensive evaluation with endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP) and ERCP with sphincter of Oddi manometry. ERCP often allows treatment of the underlying cause. Because of the inherent risks associated with ERCP, particularly when directed toward the pancreas, the role of ERCP in acute and especially recurrent pancreatitis should be primarily therapeutic with attempts to establish diagnosis whenever possible by less risky techniques including EUS and MRCP. With the added techniques, devices, skill-sets, and experience required, pancreatic endotherapy should preferably be performed in high volume tertiary referral settings. ERCP for diagnosis and treatment of severe or acute relapsing pancreatitis is also best performed using a multidisciplinary approach involving endoscopy, hepatobiliary-pancreatic surgery, and interventional radiology.

Endoscopic ultrasound-guided bile duct access for rendezvous ERCP drainage in the setting of intradiverticular papilla.

Cannulation of an intradiverticular papilla during endoscopic retrograde cholangiopancreatography (ERCP) can be challenging. We present here a technique for endoscopic ultrasound-guided puncture of the common bile duct followed by rendezvous ERCP for biliary drainage through the native intradiverticular papilla.

Accurate diagnosis of pancreas divisum by linear-array endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: During linear-array endoscopic ultrasonography (EUS), the main pancreatic duct can be followed continuously from the major papilla into the pancreatic body in most patients. Often, the duct can also be seen crossing a sonographic border between the ventral and dorsal pancreatic anlagen. It was hypothesized that the presence of either feature excludes pancreas divisum, whereas the absence of these features suggests complete pancreas divisum. PATIENTS AND METHODS: Pancreas divisum was sought during all linear-array EUS examinations conducted between July 1999 and June 2003. Charts were reviewed retrospectively, and patients who underwent endoscopic retrograde pancreatography after, but not before, EUS were included in the study. RESULTS: A total of 162 patients had EUS before ERCP. Adequate evaluation of the pancreatic duct was possible in 78 % of the patients. The prevalence of pancreas divisum was 13.6 %. In patients with adequate duct visualization, the sensitivity, specificity, and positive and negative predictive values for EUS were 95 %, 97 %, 86 %, and 99 %, respectively. The overall accuracy of EUS for identifying pancreas divisum was 97 % in this subgroup. CONCLUSION: Adequate EUS evaluation of pancreas divisum was possible in most cases. Linear-array EUS is a promising diagnostic test for pancreas divisum.

Clinical implications of postsurgical adhesions.

Adhesion development can have a major impact on a patient's subsequent health. Adhesions are a significant source of impaired organ functioning, decreased fertility, bowel obstruction, difficult re-operation, and possibly pain. Consequently, their financial sequelae are also extraordinary, with more than one billion dollars spent in the USA in 1994 on the bowel obstruction component alone. Performing adhesiolysis for pain relief appears efficacious in certain subsets of women. Unfortunately even when lysed, adhesions have a great propensity to reform. Adhesions are prevalent in all surgical fields, and nearly any compartment of the body. For treatment of infertility and recurrent pregnancy loss, lysis of intrauterine adhesions results in improved fecundability and decreased pregnancy loss.

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

BACKGROUND: Post-ERCP pancreatitis is poorly understood. The goal of this study was to comprehensively evaluate potential procedure- and patient-related risk factors for post-ERCP pancreatitis over a wide spectrum of centers. METHODS: Consecutive ERCP procedures were prospectively studied at 11 centers (6 private, 5 university). Complications were assessed at 30 days by using established consensus criteria. RESULTS: Pancreatitis occurred after 131 (6.7%) of 1963 consecutive ERCP procedures (mild 70, moderate 55, severe 6). By univariate analysis, 23 of 32 investigated variables were significant. Multivariate risk factors with adjusted odds ratios (OR) were prior ERCP-induced pancreatitis (OR 5.4), suspected sphincter of Oddi dysfunction (OR 2.6), female gender (OR 2.5), normal serum bilirubin (OR 1.9), absence of chronic pancreatitis (OR 1.9), biliary sphincter balloon dilation (OR 4.5), difficult cannulation (OR 3.4), pancreatic sphincterotomy (OR 3.1), and 1 or more injections of contrast into the pancreatic duct (OR 2.7). Small bile duct diameter, sphincter of Oddi manometry, biliary sphincterotomy, and lower ERCP case volume were not multivariate risk factors for pancreatitis, although endoscopists performing on average more than 2 ERCPs per week had significantly greater success at bile duct cannulation (96.5% versus 91.5%, p = 0.0001). Combinations of patient characteristics including female gender, normal serum bilirubin, recurrent abdominal pain, and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis, regardless of whether ERCP was diagnostic, manometric, or therapeutic. CONCLUSIONS: Patient-related factors are as important as procedure-related factors in determining risk for post-ERCP pancreatitis. These data emphasize the importance of careful patient selection as well as choice of technique in the avoidance of post-ERCP pancreatitis.

Dilation of high-grade pancreatic and biliary ductal strictures with small-caliber angioplasty balloons.

BACKGROUND: Pancreatic and bile duct strictures may be too stenotic to allow passage of conventional endoscopic dilators. METHODS: Four patients with strictures (3 pancreatic, 1 biliary) that could not be traversed with conventional endoscopic dilating devices, or in 1 case by a Soehendra stent extractor, underwent stricture dilation with a 3.3F peripheral angioplasty balloon to a maximum diameter of 6 mm. OBSERVATIONS: All strictures in the 4 patients were successfully traversed and dilated and stents were placed with resolution of the presenting clinical problem. CONCLUSIONS: Small-caliber angioplasty balloons are useful for dilation with subsequent stent placement of pancreatic and biliary strictures that are refractory to standard endoscopic approaches.

Training and competence in gastrointestinal endoscopy.

Patients, physicians, and health care providers want assurances that individuals performing gastrointestinal endoscopic procedures are competent and adequately credentialed. Definition of competence, however, has been an elusive goal. Most organizations, including professional societies and hospital privileging committees, have relied on estimated numbers of procedures performed or subjective assessment by a proctor as a surrogate marker of competence. Increasingly, objective assessment of performance is recognized as important in determining competence. Recent data have shown that learning curves for trainees are substantially more gradual than generally thought, and that the number of procedures required to achieve basic technical proficiency is much higher. Emerging data demonstrate that there is substantial variation in outcomes of endoscopy in clinical practice, related in part to the prior training, subspecialty background, ongoing case volume, and the individual endoscopist. Outcome variations correlate with both technical success and complications. Strategies for assessing competence in trainees and those in practice include numbers of procedures performed, subjective or objective assessment by a proctor, and self-assessment by the trainee. In the future, it is hoped that computers will be increasingly used to document outcomes of endoscopy in training and clinical practice as a part of routine report generation.