Classification of probe-based confocal laser endomicroscopy findings in pancreaticobiliary strictures.

BACKGROUND AND STUDY AIMS: The accurate diagnosis of indeterminate pancreaticobiliary strictures presents a clinical dilemma. Probe-based confocal laser endomicroscopy (pCLE) offers real-time in vivo microscopic tissue examination that may increase sensitivity for the detection of malignancy. the objective of this study was to develop and validate a standard descriptive classification of pcle in the pancreaticobiliary system. PATIENTS AND METHODS: A total of 102 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with pCLE to assess indeterminate pancreaticobiliary strictures were enrolled in a multicenter registry; 89 of these patients were evaluable. Information and data on the following were collected prospectively: clinical, ERCP, tissue sampling, pCLE, and follow-up. A uniform classification of pCLE findings ("Miami Classification") was developed, consisting of a set of image interpretation criteria. Thereafter, these criteria were tested through blinded consensus review of 112 randomized pCLE videos from 47 patients, and inter-observer variability was assessed in 42 patients . RESULTS: A consensus definition of the specific criteria of biliary and pancreatic pCLE findings for indeterminate strictures was developed. Single-image interpretation criteria did not have a high enough sensitivity for predicting malignancy. However, combining two or more criteria significantly increased the sensitivity and predictive values. The characteristics most suggestive of malignancy included the following: thick white bands (>20 µm), or thick dark bands (>40 µm), or dark clumps or epithelial structures. These provided sensitivity, specificity, positive predictive value, and negative predictive value of 97%, 33%, 80%, and 80% compared with 48%, 100%, 100%, and 41% for standard tissue sampling methods. Inter-observer variability was moderate for most criteria. CONCLUSION: The Miami Classification enables a structured, uniform, and reproducible description of pancreaticobiliary pCLE. Combining individual characteristics improves the sensitivity for the detection of malignancy.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS: The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS: Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS: Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS: In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures.

BACKGROUND: Brush cytology, routinely performed at ERCP to assess malignant-appearing biliary strictures, is limited by relatively low sensitivity and negative predictive value. This study assessed whether the combination of stricture dilation, endoscopic needle aspiration, and biliary brushing improves diagnostic yield. METHODS: In a prospective nonrandomized study, 46 consecutive patients were evaluated with malignant-appearing biliary strictures at ERCP. Twenty-four patients (Group A) underwent standard brush cytology alone and 22 patients (Group B) underwent stricture dilatation to 10F, endoscopic needle aspiration, and subsequent biliary brushing by using the Howell biliary system. The diagnostic yields for both techniques were compared. RESULTS: Of the 46 patients, 34 had proven malignant strictures (14 Group A, 20 Group B). Compared with brushing alone, the combination of stricture dilatation, endoscopic needle aspiration, and subsequent biliary brushing significantly increased both the sensitivity (57% vs. 85%, p < 0.02) and specificity (80% vs. 100%, p < 0.02) of cytology with positive brushings in all patients with pancreatic or gallbladder carcinoma. CONCLUSIONS: The combination of stricture dilation, endoscopic needle aspiration, and biliary brushing significantly improves diagnostic yield for malignant bile duct strictures and may particularly be of benefit for extrinsic strictures caused by pancreatic or gallbladder carcinoma.

Is CT angiography sufficient for prediction of resectability of periampullary neoplasms?

The optimal preoperative evaluation of periampullary neoplasms remains controversial. The aim of this study was to analyze the accuracy of helical computed tomography (CT) and CT angiography with three-dimensional reconstruction in predicting resectability. Between March 1996 and May 1999, a total of 100 patients with periampullary neoplasms were prospectively staged by helical CT and CT angiography with three-dimensional reconstruction. Vascular involvement was graded from 0 to 4, with grade 0 representing no vascular involvement and grade 4 total encasement of either the superior mesenteric vein or artery. Patients with grade 4 lesions were considered unresectable. Sixty-eight patients underwent surgical exploration with intent to perform a pancreaticoduodenectomy. Forty-four lesions were grade 0, five were grade l, eight were grade 2, and 11 were grade 3. Resectability for grades 0 to 3 was 96%, 100%, 50%, and 9%, respectively, for an overall resectability rate of 76%. Resectability in patients with vascular encroachment (grade 2) is usually determined by the extent of local disease rather than the presence of extrapancreatic disease. Resection is rarely possible in patients with evidence of vascular encasement (grade 3). Additional imaging modalities such as diagnostic laparoscopy are superfluous in patients with no evidence of local vascular involvement on CT angiography (grades 0 and 1) because of the high resectability rate and infrequency of unsuspected distant metastatic deposits.

Multiplanar CT pancreatography and distal cholangiography with minimum intensity projections.

PURPOSE: To develop a technique of projectional computed tomographic (CT) cholangiopancreatography (CTCP). MATERIALS AND METHODS: Sixty-one patients underwent CT for suspected biliary or pancreatic abnormalities. The axial CT and CTCP techniques included spiral scanning during the portal venous phase and thick-slab minimum intensity projections. Visualization of pancreatic and extrahepatic bile ducts (divided in five duct segments per patient) was graded blindly on a scale of 1-5 by a consensus of two radiologists. Two hundred seventy-seven duct segments were used to compare axial CT and CTCP in the depiction of duct segments and dilatation; 109 segments were used to compare CTCP with ERCP. RESULTS: Fifty-six of 277 duct segments were not visualized on axial CT images; 15 segments were not visualized on CTCP images (P < .001). There was no statistically significant difference between the number of segments missed with ERCP and the number missed with CTCP: nine and three of 109 segments, respectively. Duct visualization was equal on axial CT and CTCP images in 35 of 109 duct segments and was superior on CTCP images in all but one of the remaining segments (P < .001). Duct visualization on CTCP images was equal to that on ERCP images in 35 segments, superior in nine, and significantly inferior in 66 (P < .001). CONCLUSION: CTCP improves CT depiction of pancreatic and bile ducts with a quality that approaches that of ERCP.

MR cholangiopancreatography after unsuccessful or incomplete ERCP.

PURPOSE: To assess the value of magnetic resonance (MR) cholangiopancreatography in patients in whom endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessful or did not completely delineate ductal abnormalities. MATERIALS AND METHODS: MR cholangiopancreatography was performed in 37 consecutive patients because ERCP was unsuccessful (n = 20), postsurgical biliary-enteric anatomy was present (n = 10), or evidence of complete pancreatic duct obstruction was found ar ERCP (n = 7). RESULTS: MR cholangiopancreatography was successful in all patients. Eleven patients had normal MR findings and required no further intervention. Eight patients has abnormalities that were detected with MR but were followed up clinically. Eleven patients subsequently underwent laparotomy, three underwent therapeutic percutaneous transhepatic cholangiography (PTC), two underwent diagnostic (PTC), and one underwent ultrasound-guided biopsy. CONCLUSIONS: MR cholangiopancreatography plays an important role in the care of patients in whom ERCP is unsuccessful or incomplete and when technical difficulties can be anticipated.

MR cholangiopancreatography: efficacy of three-dimensional turbo spin-echo technique.

OBJECTIVE: The purpose of this study was to correlate a new three-dimensional turbo spin-echo MR cholangiopancreatography technique with endoscopic cholangiopancreatography or percutaneous cholangiography to determine the efficacy of the new technique for visualizing and diagnosing diseases of the pancreatic and biliary ducts. It was hypothesized that the new technique would provide diagnostic images without prolonged breath holding or a surface coil as required by previous MR techniques. SUBJECTS AND METHODS: We describe a respiratory-triggered, heavily T2-weighted, three-dimensional, multislab turbo spin-echo sequence for MR cholangiopancreatography. Thirty patients with suspected biliary or pancreatic disease were randomly selected from referrals for endoscopic retrograde cholangiopancreatography. All patients were imaged with the optimized MR technique prior to attempted endoscopic or percutaneous cholangiopancreatography. The MR images were evaluated without additional clinical or radiographic information by consensus opinion of two of the authors for visualization and caliber of the ducts. When the ducts were abnormal, the level and probable cause were categorized as follows: normal, periampullary stricture, localized duct stenosis, multifocal strictures, calculous disease, duct anomalies, and cystic disease. The images obtained by conventional percutaneous or endoscopic cholangiopancreatography were evaluated in the same manner with the exception that additional clinical and radiologic information was provided. The diagnostic categories determined by MR and direct cholangiopancreatography were compared. Patients were included in the analysis only if endoscopic or percutaneous opacification of the biliary or pancreatic ducts was successful. RESULTS: Diagnostic MR images were obtained in 29 (97%) of 30 patients. Endoscopic or percutaneous cholangiopancreatography was successful in 21 of the 29 patients for the common bile duct and in 17 of the 29 patients for the pancreatic duct. The diagnosis for the common bile duct by the MR technique agreed with the diagnosis by endoscopic or percutaneous cholangiopancreatography in 19 (90%) of 21 patients. For diagnosis of diseases of the pancreatic duct, there was agreement in 15 (88%) of 17 patients. CONCLUSION: Respiratory-triggered, multislab, three-dimensional turbo spin-echo MR cholangiopancreatography is a noninvasive technique for visualization of the pancreatic and biliary ductal systems. It is capable of providing diagnostic information equivalent to invasive techniques in a large percentage of patients and should be the technique of choice when invasive techniques are incomplete, unsuccessful, or technically difficult.

Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans.

Nitric oxide (NO) is an inhibitor of gastrointestinal smooth muscle. Model systems of the gut predict the NO will complex with biological thiol (SH) groups, yielding S-nitrosothiols (RS-NO), which may limit the propensity to form mutagenic nitrosamines. The inhibitory effects of NO and its biologically relevant adducts on sphincter of Oddi (SO) motility have been inferred from animal studies; however, their importance in regulating human SO is not known. The objectives of this study were to (a) provide histologic confirmation of nitric oxide synthase (NOS) in human SO; (b) characterize the pharmacology of S-nitroso-N-acetylcysteine (SNAC), an exemplary S-nitrosothiol, on SO motility in a rabbit model; and (c) study the effects of topical SNAC on SO motility in humans. Immunocytochemical and histochemical identification of NOS was performed in human SO. The pharmacologic response of SNAC was defined in isolated rabbit SO using a standard bioassay. Topical SNAC was then applied to the duodenal papilla in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and biliary manometry. NOS was localized to nerve fibers and bundles of the SO in rabbits and humans. SNAC inhibited spontaneous motility (frequency and amplitude) as well as acetylcholine-induced elevations in SO basal pressure in the rabbit model. In patients undergoing ERCP and biliary manometry, topical SNAC inhibited SO contraction freqency, basal pressure, and duodenal motility. NOS is localized to neural elements in human SO, implicating a role for NO in regulating SO function. Supporting this concept, SNAC is an inhibitor of SO and duodenal motility when applied topically to humans during ERCP. Our data suggest a novel clinical approach using local NO donors to control gastrointestinal motility and regulate sphincteric function.