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.

Fibroinflammatory biliary stricture: a rare bile duct lesion masquerading as cholangiocarcinoma.

INTRODUCTION: Fibroinflammatory biliary stricture (FIBS) is a rare benign tumor-like process of the extrahepatic bile duct that masquerades as cholangiocarcinoma. METHODS: In order to distinguish this unusual entity from cancer, we performed a systematic analysis of 11 patients with FIBS. All patients presented with jaundice; six patients had coexisting autoimmune disease. Preoperative evaluation included computed tomography scan and endoscopic retrograde cholangiopancreatography with benign brush cytology. Surgical treatment included nine bile duct resections with five concurrent liver resections and two incisional biopsies. Light microscopy demonstrated fibrous lesions admixed with chronic inflammation. RESULTS AND DISCUSSION: Immunohistochemistry demonstrated smooth muscle actin expression in all lesions except one; five tumors exhibited IgG4 positive plasma cells. The lesions were negative for cytokeratin, ALK1, CD21, S100, Ki67, and p53. Six patients received postoperative immunosuppression. At 41 month median follow-up (range 15-58 months), there was no evidence of recurrent FIBS in ten patients, while one was lost to follow-up. CONCLUSION: FIBS is a rare myofibroblastic lesion with an immunohistochemical profile distinct from other epithelial and stromal neoplasms of the extrahepatic bile duct. A subset of these cases appear to represent IgG4-related sclerosing cholangitis. Because preoperative cytology is not diagnostic of FIBS, surgical resection remains the mainstay of diagnosis and treatment, while immunosuppression may reduce the risk of recurrence.

Multianalyte profiling of serum cytokines for detection of pancreatic cancer.

Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a panel, we have utilized a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple markers. In this study, a panel of 31 serological markers including cytokines, chemokines, growth and angiogenic factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer patients, patients with chronic pancreatitis, and matched control healthy subjects. Statistical analysis identified a multicytokine panel that was able to distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7% and specificity of 92.3%, which was superior to performance of CA 19-9 alone. Importantly, a multicytokine panel allowed the discrimination of pancreatic cancer from chronic pancreatitis with high sensitivity of 98% and specificity of 96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines using a novel LabMAP technology is a promising approach for development of a diagnostic assay for pancreatic cancer.

Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples.

BACKGROUND: Brush cytology of biliary strictures to diagnose pancreaticobiliary malignancy suffers from poor sensitivity. AIM: To improve the diagnostic yield of pancreaticobiliary brush cytology through analysis of tumour suppressor gene linked microsatellite marker loss of heterozygosity (LOH) and k-ras codon 12 mutation detection. METHODS: Twenty six patients with biliary strictures underwent endoscopic retrograde cholangiography with brush cytology. A panel of 12 polymorphic microsatellite markers linked to six tumour suppressor genes was developed. Genomic DNA from cell clusters acquired from brush cytology specimens and microdissected surgical malignant and normal tissue underwent polymerase chain amplification reaction (PCR). PCR products were compared for LOH and k-ras codon 12 mutations. RESULTS: Seventeen patients were confirmed to have pancreaticobiliary adenocarcinoma. Nine patients had benign strictures (eight proven surgically, one by follow up). Cytomorphological interpretation was positive for malignancy (n = 8), indeterminate (n = 10), and negative for malignancy (n = 8). Selected malignant appearing cytological cell clusters and microdissected histological samples from cancer showed abundant LOH characteristic of malignancy while brushings from nine cases without cancer carried no LOH (p<0.001). LOH and k-ras mutations profile of the cytological specimens was almost always concordant with the tissue samples. Presence of k-ras mutation predicted malignancy of pancreatic origin (p<0.001). CONCLUSION: LOH and k-ras codon 12 mutation analysis of PCR amplified DNA from biliary brush cytology discriminates reactive from malignant cells, with 100% sensitivity, specificity, and accuracy. Minor variations in LOH in brushings and in different sites within the same tumour likely reflect intratumoral mutational heterogeneity during clonal expansion of pre- and neoplastic lineages.

Endoscopic balloon dilation of gastroenteric anastomotic stricture after laparoscopic gastric bypass.

BACKGROUND AND STUDY AIMS: Laparoscopic gastric bypass is a recently introduced treatment option for morbid obesity, with promising initial results. Stenosis of the gastroenterostomy is a recognized complication. The efficacy and safety of endoscopic balloon dilation for the management of this type of anastomotic stenosis has not been studied. PATIENTS AND METHODS: 450 patients who underwent laparoscopic gastric bypass at our institution were followed prospectively. All patients had a 15 ml gastric pouch and either a 75 cm or 150 cm jejunal Roux limb depending on whether obesity was morbid (body mass index (BMI) < 50 kg/m 2) or super-morbid (BMI > 50 kg/m 2). Patients who developed symptoms compatible with stenosis of the gastrojejunostomy were referred for upper gastrointestinal endoscopy. RESULTS: 14 patients, 11 women and three men, underwent a total of 27 endoscopies, with 23 balloon dilations. Their average age was 46 years (range 33 - 59 years), average preoperative BMI was 47 kg/m 2, and they presented an average of 2.7 months after surgery (range 0.3 - 15.7 months). Of the 14 patients, 13 had a stricture of the gastrojejunostomy and one patient had edema. For initial dilation, a 15 mm hydrostatic balloon was used in 12 patients and an 18 mm balloon in two patients. There was response to treatment with the 15 mm balloon in seven of the 12 patients (58 %), and they required no further dilation; in one there was a response to a further 15 mm balloon dilation; in three patients a response to subsequent 18 mm balloon dilation; and one patient required 18 mm and 25 mm balloon dilations. The two patients treated with an initial 18 mm balloon dilation required no further dilations. The average length of follow-up after successful dilation was 18 months (range 7 - 30 months). There were no complications with any of the 23 dilations performed. CONCLUSION: Stenosis of the gastroenterostomy after laparoscopic gastric bypass occurred in 3.1 % of the patients in this series. It can be successfully and safely treated with endoscopic balloon dilation with good long-term follow-up.

Safety of ERCP during pregnancy.

OBJECTIVES: There are few data in the literature regarding the indications, therapy, and safety of endoscopic management of pancreatico-biliary disorders during pregnancy. We report the largest single center experience with ERCP in pregnancy. METHODS: We reviewed 15 patients that underwent ERCP during pregnancy. In all patients, the pelvis was lead-shielded and the fetus was monitored by an obstetrician. Fluoroscopy was minimized and hard copy radiographs taken only when essential. RESULTS: The mean patient age was 28.9 yr (15-36 yr). The mean duration of gestation was 25 wk (12-33 wk); one patient was in the first, five in the second, and nine in the third trimester. The indications were gallstone pancreatitis (n = 6), choledocholithiasis on ultrasound (n = 5), elevated liver enzymes and a dilated bile duct on ultrasound (n = 2), abdominal pain and gallstones (n = 1), and chronic pancreatitis (n = 1). ERCP findings were bile duct stones (n = 6), patulous papilla (n = 1), bile duct debris (n = 1), normal bile duct and gallstones or gallbladder sludge (n = 3), dilated bile duct and gallstones (n = 1), normal bile duct and no gallstones (n = 2), and chronic pancreatitis (n = 1). Six patients underwent sphincterotomies and one a biliary stent insertion. One sphincterotomy was complicated by mild pancreatitis. All infants delivered to date have had Apgar-scores >8, and continuing pregnancies are uneventful. Mean fluorosocopy time was 3.2 min (SD +/- 1.8). An estimated fetal radiation exposure was 310 mrad (SD +/- 164) which is substantially below the accepted teratogenic dose. CONCLUSIONS: ERCP in pregnancy seems to be safe for both mother and fetus; however, it should be restricted to therapeutic indications with additional intraprocedure safety measures.

Effectiveness of the Ultraflex Diamond stent for the palliation of malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Endoscopically placed metallic biliary stents provide durable drainage for malignant biliary obstruction. The best-studied metal stent is the Wallstent, which has a greater duration of patency than polyethylene stents. Recently, the Ultraflex Diamond stent has been introduced, with reports from Europe which suggest efficacy similar to that of the Wallstent. We report our experience with this new metal stent and compare it with a historical cohort of Wallstent-treated patients. PATIENTS AND METHODS: Between July 1997 and July 1998 all metal stents placed for malignant biliary obstruction were Diamond stents (10 mm diameter, 6 or 8 cm length). Prospective follow-up details with regard to patient death or stent occlusion were obtained. In total, 32 patients underwent stenting, but 11 patients were excluded because of the following: death from pre-existing cholangitis (2); placement of bilateral hilar stents (2); placement of stent through occluded metal stents (3); failure to palliate jaundice due to complex hilar stricture (2) or concomitant liver failure (1); or inability to obtain follow-up (1), leaving 21 patients for analysis. Occlusion rates and stent patency were also determined retrospectively for 19 patients with malignant biliary obstruction who had Wallstents (10 mm diameter, 6.8 cm length) placed during the preceding year and for whom accurate and complete follow-up details were available. RESULTS: In the Diamond stent group there were 14 men and seven women, mean age 73. In the Wallstent group there were 11 men and eight women, mean age 66. The types of cancer, level of stricture and percentage with prior polyethylene stenting were similar in both groups. Stent occlusion occurred in 9/21 (43%), Diamond stents at a mean of 74 +/- 43 days compared with 8/19 (42%) Wallstents at a mean of 178 +/- 138 days (P < 0.04). Mean time of stent patency was 110 +/- 89 days for Diamond stents and 253 +/- 218 days for Wallstents (P < 0.01). Analysis of occlusion-free survival using a Kaplan-Meier plot showed a trend favoring the Wallstent (P = 0.12; Wilcoxon test). CONCLUSIONS: The occlusion rate and patency of Diamond stents for malignant biliary obstruction appear to be inferior to those of Wallstents and similar to reported values for polyethylene stents. Prospective randomized comparisons of Wallstents and newer self-expanding metal stents are warranted.

Intracranial ossifications and microangiopathy at 8 Tesla MRI.

UNLABELLED: Clinical evaluation and MR imaging of microangiopathy associated with hypertension is limited. We describe a case that illustrates sensitivity of MRI at 8 Tesla for imaging of microvasculature, iron, calcium deposits and silent white matter lesions (WML). A 60-year-old black hypertensive woman was evaluated for numbness in the face and extremities. MRI at 1.5 Tesla was unrevealing.MRI at 8 Tesla: Axial and sagittal Gradient Echo images were obtained with an 8T/80 cm human scanner and showed: 1) Large areas of signal voids due to ossifications and fat deposits within the falx. 2) Obstructed small vessels in the periventricular regions and distended cortical veins. 3) Numerous small WML, suggestive of mini-infarcts (<1 cm) and microhemorrhages. 4) Intracranial calcifications in the falx, tentorium, basal ganglia and chorioid plexus that were confirmed by CT scan. Atherosclerotic plaque in right carotid artery and reduced vasomotor reserve in middle cerebral arteries, documented by ultrasound, indicated large and small vessel disease. CONCLUSIONS: MRI at 8 Tesla improves visualization of microangiopathy, ossifications and iron deposits due to enhanced magnetic susceptibility at ultra high magnetic field.

Using CT and cholangiography to diagnose biliary tract carcinoma complicating primary sclerosing cholangitis.

OBJECTIVE: The objective of our study was to determine the value of CT and cholangiography for diagnosing biliary tract carcinoma complicating primary sclerosing cholangitis. MATERIALS AND METHODS: One hundred thirteen abdominal CT examinations and cholangiograms in 45 patients with primary sclerosing cholangitis, including 18 patients with established biliary tract carcinoma, were analyzed for tumor. Four radiologists who were unaware of the presence or absence of carcinoma rated each study as to the probability of malignancy. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of CT and cholangiography, the value of imaging signs, and the degree of inter-observer variation in interpretation. Sensitivity and specificity values were calculated. RESULTS: CT outperformed cholangiography in the detection of carcinoma. The average area under the receiver operating characteristic curve was 0.82 for CT and 0.57 for cholangiography (p = 0.003). Sensitivity and specificity for detecting carcinoma using CT were good, with average values of 82% and 80%, respectively. Average sensitivity and specificity for cholangiography were 54% and 53%, respectively. The most reliable sign of tumor on CT was a discrete mass. Progressive biliary dilatation on sequential studies was the most useful sign on cholangiography. Interobserver agreement assessed using the Cronbach alpha was fair for cholangiography and good for CT. CONCLUSION: CT provides good sensitivity and specificity and significantly outperforms cholangiography in detecting biliary tract carcinoma complicating primary sclerosing cholangitis. Despite limitations, CT and cholangiography provide useful information not otherwise available in the treatment of patients with primary sclerosing cholangitis.

Santorinicele in pancreas divisum: diagnosis with secretin-stimulated magnetic resonance pancreatography.

A Santorinicele, or cystic dilatation of the dorsal pancreatic duct at the minor papilla, is seen in a small number of patients with pancreas divisum and may indicate obstruction at the minor papilla, a risk factor for pancreatitis. We present a case of a Santorinicele that was diagnosed with secretin-stimulated magnetic resonance pancreatography and treated with minor papillotomy.