Accuracy of magnetic resonance cholangiopancreatography in the diagnosis of pancreas divisum.

BACKGROUND: Patients with pancreas divisum may develop pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing pancreas divisum. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive test reported to be highly accurate in diagnosing pancreas divisum. AIM: To evaluate the diagnostic accuracy of MRCP in detecting pancreas divisum at our institution. METHODS: We reviewed patients who underwent both ERCP and MRCP. Patients who had diagnostic endoscopic pancreatograms (ERP) after MRCP comprise the study population. Secretin was given in 113/146 patients (S-MRCP). The remaining 33/146 patients had MRCP without secretin. In 7/33 patients who underwent MRCP without secretin (21.2%), the studies were non-diagnostic and, therefore, this group was not further analyzed and the study focused on the S-MRCP group only. RESULTS: ERP identified pancreas divisum in 19/113 (16.8%) patients. S-MRCP identified 14/19 pancreas divisum and was false-positive in three cases (sensitivity 73.3%, specificity 96.8%, positive predictive value 82.4%, negative predictive value 94.8%). Of the eight patients with inaccurate S-MRCP, 5 (63%) had changes of chronic pancreatitis by ERP. This differs from the frequency of chronic pancreatitis by ERP in 24/105 (23%) patients with accurate MRCP findings. The ERCP findings of chronic pancreatitis were more frequent among incorrect S-MRCP interpretations than among correct interpretations (odds ratio [OR] 5.5 [95% confidence interval (CI) 1.3-25.3]). MRCP without secretin is non-diagnostic for pancreas divisum in a significant proportion of patients. S-MRCP had a satisfactory specificity for detecting pancreas divisum. However, the sensitivity of S-MRCP for the diagnosis of pancreas divisum was modest at 73.3%. This is low compared to previous smaller studies, which reported a sensitivity of MRCP of up to 100%.

A prospective study comparing rapid assessment of smears and ThinPrep for endoscopic ultrasound-guided fine-needle aspirates.

BACKGROUND AND STUDY AIMS: ThinPrep is often used for endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples but the sensitivity of this method is unknown. The objective of the study was to compare sensitivity and accuracy of ThinPrep versus the smear method in pancreas and lymph node samples obtained by EUS-FNA. PATIENTS AND METHODS: Patients with suspected malignancy in the pancreas or lymph node underwent EUS-FNA. On-site rapid assessment of all aspirates using the smear method was performed. After rapid assessment, three additional passes from each site were submitted into ThinPrep liquid medium. Cytopathologists interpreting the smear method and ThinPrep slides were blinded to each other. The gold standard was final cytology or pathology results. RESULTS: A total of 130 patients (36 % women, mean age 63 years) underwent EUS-FNA of 139 sites (50 pancreas, 89 lymph node). Malignancy was confirmed in 47 pancreas samples (94 %) and 48 lymph node samples (54 %). Mean +/- SD number of passes made for the smear method was 2.6 +/- 1.3. For pancreatic cancer, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the ThinPrep versus the smear method were: 62 % versus 98 %, 100 % versus 100 %, 100 % versus 100 %, 14 % versus 75 %, and 64 % versus 98 %, respectively. For lymph nodes the values were 67 % versus 92 %, 100 % versus 98 %, 100 % versus 98 %, 72 % versus 72 %, and 82 % versus 94 %, respectively. CONCLUSIONS: The smear method is more sensitive and accurate than ThinPrep in detecting malignancy from EUS-FNA samples of the pancreas and lymph nodes. Smear method with on-site rapid assessment should be favored over ThinPrep in suspected malignancy.

Endoscopic ultrasound-guided fine-needle aspiration with or without flow cytometry for the diagnosis of primary pancreatic lymphoma - a case series.

The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with flow cytometry for the diagnosis of primary pancreatic lymphoma (PPL) has not been previously described. Our aims were to describe the EUS features of PPL and the role of EUS-FNA with and without flow cytometry in the diagnosis of 16 patients. When EUS-FNA with flow cytometry was compared with EUS-FNA without flow cytometry, the sensitivities for diagnosing non-Hodgkin's lymphoma were 84.6 % versus 30.8 %, respectively ( P = 0.01). EUS-FNA with flow cytometry is a valuable tool to diagnose PPL. Flow cytometry analysis complements traditional assessment by standard cytology.

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.

Positron-emission tomography and computed tomography of cystic pancreatic masses.

AIM: To investigate the sensitivity and specificity of computed tomography (CT), positron-emission tomography (PET), and both methods in combination, for determining whether cystic pancreatic tumours are malignant. MATERIALS AND METHODS: We retrospectively identified all patients with cystic pancreatic tumours who underwent separate PET and contrast-enhanced CT examinations within a 1-month interval. Tumours were classified as benign or malignant on CT (two radiologists, independently), PET [a reported standardized uptake value (SUV) of 2.5 was taken as the cut-off between benign and malignant], and with PET and CT images together (two radiologists, in consensus). Readers were blinded to pathological and other radiological findings. Mean patient age and lesion size were compared between benign and malignant groups using Student's t-test. For CT findings, odds ratios (OR) and confidence intervals (CI) were calculated using multivariate logistic regression models. For CT, PET, and the combined images, sensitivities and specificities were calculated, and compared between groups using Fisher's exact test. RESULTS: Thirty patients were identified. The best CT predictor of malignancy was size; mean diameter was 2.3 cm (benign) and 4.1 cm (malignant) (p<0.01); OR was 2.80 (95% CI, 1.26-6.20). Sensitivities of CT, PET and combined PET/CT images were 67-71, 57, and 86%, respectively. PET/CT was more sensitive than PET (p<0.01) or CT (p<0.01) alone. Specificities of CT, PET, and combined PET/CT images were 87-90, 65, and 91%, respectively. PET/CT was more specific than PET (p<0.01) but not CT (p>0.05). CONCLUSION: The sensitivity and specificity of combined PET and CT images is comparable with or superior to either CT or PET alone in determining malignancy in cystic pancreatic lesions.

Endoscopic ultrasound-guided fine-needle aspiration of left adrenal gland masses.

BACKGROUND AND STUDY AIM: Although the left adrenal gland is readily visible by endoscopic ultrasound (EUS), there are few published data on the utility of EUS-guided fine-needle aspiration (EUS-FNA) of this site. The aim of this study was to report our experience of EUS-FNA of left adrenal gland masses. PATIENTS AND METHODS: In this retrospective case series, we reviewed our EUS and cytology databases to identify consecutive patients who underwent EUS-FNA of the left adrenal gland between January 1997 and January 2004. Medical records were reviewed and the results of EUS examinations and cytological investigations were abstracted. RESULTS: Our searches resulted in the identification of a series of 38 consecutive patients who underwent EUS for the evaluation of a lung mass (n = 14), a pancreatic mass (n = 14), obstructive jaundice (n = 1), dysphagia (n = 2), an ampullary adenoma (n = 1), celiac block (n = 1), or a left adrenal gland mass (n = 5). The mean maximal left adrenal mass diameter was 24 mm (range 7-66 mm). Diagnoses after EUS-FNA (the mean number of passes was 3.6) were: metastatic lung cancer (n = 2), esophageal adenocarcinoma (n = 1), melanoma (n = 1), renal cell carcinoma (n = 1), and pancreatic neuroendocrine tumor (n = 1); primary pheochromocytoma (n = 1); benign adrenal tissue (n = 21); and granulomatous inflammation (n = 1). Nine aspirations (24 %) were nondiagnostic. The absence of a discrete adrenal mass on EUS occurred more frequently in patients with nondiagnostic biopsies than in those with diagnostic biopsies (56 % vs. 7 %; odds ratio 23.4, 95 %CI 3.5 - 157.0; P = 0.004). No complications were noted. CONCLUSIONS: EUS-FNA of the left adrenal gland is safe and can be useful for the evaluation and staging of suspected malignancy. Nondiagnostic biopsies are more common when sampling diffusely enlarged glands, compared with glands with a focal mass.

Ethical issues in psychopharmacology.

The marketing of selective serotonin reuptake inhibitors in the psychopharmacological industry presents a serious moral problem for the corporate model of medicine. In this paper I examine ethical issues relating to the efficacy and safety of these drugs. Pharmaceutical companies have a moral obligation to disclose all information in their possession bearing on the true risks and benefits of their drugs. Only then can patients make fully informed decisions about their treatment.

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.

Endoscopic ultrasound for esophageal and gastroesophageal junction cancer: Impact of increased use of primary neoadjuvant therapy on preoperative locoregional staging accuracy.

Initial treatment of locally advanced esophageal and gastroesophageal junction (GEJ) malignancies for selected patients at some institutions has recently changed from surgical resection to neoadjuvant therapy. The aim of this study is to evaluate the impact of this change in treatment strategy on both the overall disease profile and locoregional endoscopic ultrasound (EUS) staging accuracy for a cohort of patients managed with primary surgical resection over a 10-year period at our institution. All subjects at our institution who underwent primary esophagectomy from 1993 to 2002 following preoperative EUS for known or suspected esophageal and/or GEJ cancers were identified. Patients with dysplasia alone, prior upper gastrointestinal tract surgery, preoperative neoadjuvant therapy, cancer of the gastric cardia or recurrent malignancy were excluded. EUS findings and staging results were compared to surgical pathology following resection. The impact of the gradually increased use of primary chemoradiation during the second half of the study was assessed. Of the 286 operations performed, 184 subjects were excluded. The remaining 102 underwent primary surgical resection a median of 18 days following EUS staging for adenocarcinoma (88%) or squamous cell carcinoma (12%) of the esophagus (69%) or GEJ (31%). Overall EUS locoregional T and N staging accuracy was 72% and 75% respectively; accuracy for T1, T2, T3 and T4 cancer was 42%, 50%, 88% and 50% respectively. Despite an increased frequency of pathologically confirmed T1 and T2 cancers (P = 0.005) and an insignificant trend toward increased N0 malignancy (P = 0.05) during the second half of the study period, no statistically significant changes in T (P = 0.07) or N (P = 0.82) staging accuracies for EUS or disease characteristics were noted between the first and second half of the study period. Despite both inaccurate radial EUS staging and increased relative use of primary surgery for early cancers, recent increased use of primary neoadjuvant therapy did not change overall disease characteristics and accuracy of locoregional EUS staging of esophageal and GEJ cancers managed with primary surgical resection.

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.

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.

Developing unit-specific credentialing.

A systematic plan can streamline the certification process. A self-directed team identified, developed and implemented the components needed to make the workload manageable. The actual process for developing a unit-based credentialing system in a special care unit is described.

Overexpression of deltaEmBP, a truncated dominant negative version of the wheat G-box binding protein EmBP-1, alters vegetative development in transgenic tobacco.

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.

Adenosine A1 and A2b receptors coupled to distinct interactive signaling pathways in intestinal muscle cells.

Adenosine receptors and the signaling pathways to which they are coupled were examined in dispersed intestinal muscle cells. The receptors were characterized by their ability to induce contraction or relaxation, mobilize Ca2+ and stimulate or inhibit cAMP, in naive cells and in cells where only one receptor type was preserved by selective receptor protection. Adenosine elicited contraction and increased [Ca2+]i and cAMP; the contraction was mimicked by the A1 selective agonist, cyclopentyladenosine. A selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine, and pertussis toxin abolished contraction and the increase in [Ca2+]i and augmented the increase in cAMP. Conversely, a preferential A2 antagonist, 9-chloro-2-(2-furyl) [1,2,4]triazolo[1,5-c]quinazolin-5-amine augmented contraction and the increase in [Ca2+]i and abolished the increase in cAMP; a cAMP-kinase inhibitor, Rp-cAMP[S], had a similar effect, augmenting contraction and the increase in [Ca2+]i. Adenosine elicited also relaxation of maximally contracted cells that increased or decreased in parallel with cAMP. The selective A2a agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine, was a very weak relaxant agent, and the selective A2a antagonist, 8-(3-chlorostyryl)caffeine, had no effect on adenosine-induced relaxation. In cells where only A1 receptors were preserved, the cAMP response to adenosine was abolished, although contraction and [Ca2+]i were increased to the same extent as when naive cells were treated with the A2 antagonist. Conversely, in cells where only A2 receptors were preserved, contraction and the increase in [Ca2+]i were abolished and the increase in cAMP was augmented to the same level as when naive cells were treated with the A1 antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous endoscopic gastrojejunostomy: a dual center safety and efficacy trial.

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.