mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN).

OBJECTIVE: Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation. DESIGN: mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot. RESULTS: Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p<0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively. CONCLUSIONS: mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification.

A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction.

BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.

Cytological and cyst fluid analysis of small (< or =3 cm) branch duct intraductal papillary mucinous neoplasms adds value to patient management decisions.

BACKGROUND/AIM: Management of patients with small (1-3 cm) branch duct intraductal papillary mucinous neoplasms (IPMN) is a challenge. Symptoms, dilated duct, mural nodule or positive cytology have been proposed as parameters for resection. The aim of our study was to compare this proposed algorithm to one that incorporates cytology with less than malignant epithelial cells and cyst fluid carcinoembryonic antigen (CEA). METHODS: A retrospective study was conducted. RESULTS: There were 14 nonmalignant and 6 malignant cysts with 3 invasive IPMN. None were associated with a dilated duct and none had positive cytology. Only a mural nodule was significant by univariate analysis for the detection of malignancy (p = 0.01) and invasion (p = 0.009). The detection of atypical epithelial cells or a cyst fluid CEA of >2,500 ng/ml was more accurate for the detection of malignancy than using the recommended algorithm. CONCLUSIONS: The presence of a mural nodule in a small branch duct IPMN is a predictor of malignancy and invasion by univariate analysis. Recognition of an atypical epithelial cell component in contrast to positive cytology or a cyst fluid CEA of >2,500 ng/ml is more accurate than the recommended algorithm and adds value to the preoperative assessment of clinically diagnosed small branch duct IPMN. and IAP.

EUS staging of upper GI malignancies: results of a prospective randomized trial.

BACKGROUND: Electronic 270 degrees transverse-array EUS (TA-EUS) provides high-quality cross-sectional images but cannot guide FNA. Linear EUS (L-EUS) provides longitudinal images of malignancies and the ability to guide FNA. OBJECTIVE: We conducted a prospective randomized comparison of TA-EUS and L-EUS for the staging of upper-GI (UGI) malignancies. DESIGN: Forty-three patients underwent L-EUS immediately followed by TA-EUS (N = 27, 63%) or TA-EUS immediately followed by L-EUS (N = 16, 37%). PATIENTS: Forty-three subjects (mean age, 64 years; 37 men) with an UGI malignancy (4 stomach and 38 esophageal) were evaluated with both TA-EUS and L-EUS. INTERVENTIONS: Abnormal lymph nodes were sampled by FNA for cytology. RESULTS: There was agreement on the T stage by linear and radial techniques in 38 of 43 subjects (88%). Twenty-seven of 43 patients (63%) had abnormal lymph nodes by linear or transverse-array imaging. L-EUS demonstrated 66 abnormal lymph nodes in 27 subjects (average of 2.4 nodes/subject). TA-EUS demonstrated 90 abnormal lymph nodes in 27 subjects (average of 3.3 nodes/subject, P = .009, compared with L-EUS). In 16 of the 27 subjects, an FNA was performed, which was positive in 13 cases (81%) and negative in 3 cases (10%) for malignancy. CONCLUSIONS: TA-EUS and L-EUS provide similar results of T staging of UGI malignancies. However, the number of abnormal lymph nodes detected by TA-EUS was more than by L-EUS. These findings suggest that radial or transverse-array EUS imaging should be the primary method for staging of UGI malignancies.

Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade. METHODS: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis. RESULTS: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002). CONCLUSIONS: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Ethanol lavage of pancreatic cystic lesions: initial pilot study.

BACKGROUND: Ethanol lavage has been used to successfully and safely ablate cystic lesions of the liver, the kidneys, and the thyroid. METHODS: Asymptomatic patients who undergo EUS examination for a pancreatic cystic lesion were eligible. Patients underwent complete examination with a linear-array echoendoscope, and cyst characteristics were documented. After evacuation of the cyst with needle aspiration, the cyst cavity was lavaged with ethanol for 3 to 5 minutes. The concentration (5%-80%) of ethanol was gradually increased over the course of the study. Patients were monitored for complications during 2 hours after the procedure, and further follow-up was obtained at 72 hours and 1 year after lavage. OBSERVATIONS: Twenty-five patients were enrolled, 80% were women, and the mean age of all patients was 64.5 years. Cysts had a mean diameter of 19.4 mm and were equally located in the head, the body, and the tail of the pancreas. Cyst-fluid characteristics included high viscosity in 13 (52%) and a mean carcinoembryonic antigen and amylase of 5916 ng/mL and 11,506 U/L, respectively. None of the patients reported any symptoms in short- and long-term follow-up. Of the 23/25 patients with complete follow-up, 8 patients (35%) had complete resolution of their cysts on follow-up imaging. Five patients underwent resection, and histologic evidence of epithelial ablation was seen. CONCLUSIONS: Ethanol lavage of pancreatic cystic lesions is safe and feasible. A subset of patients undergoing ethanol lavage appears to have long-term resolution on follow-up imaging. Further prospective studies are required to determine if ethanol lavage is an effective treatment for pancreatic cystic lesions.

EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) of pancreatic cysts is considered safe, however, data are conflicting regarding complication rates. The aim of this study was to determine the complication rate of EUS-guided pancreatic cyst aspiration and predictors of these complications. METHODS: Results of pancreatic cyst EUS FNA at 2 academic institutions from March 1996 to October 2003 were reviewed. A total of 603 patients with 651 pancreatic cysts were evaluated. Complications were identified from clinic, emergency department, and discharge notes, and laboratory and radiologic data. Data collected were as follows: cyst size, location, septations, diagnosis, number of passes, needle size, status as inpatient or outpatient, performance of same-day endoscopic retrograde cholangiopancreatography (ERCP), and use of prophylactic antibiotics. RESULTS: Complications were identified in 13 patients (2.2%, 13 of 603): 6 patients had pancreatitis, 4 patients had abdominal pain, 1 patient had a retroperitoneal bleed, 1 patient had an infection, and 1 patient had bradycardia. Twelve patients required hospitalization, with an average length of stay of 3.8 +/- 1.1 days. Type of cyst, size, presence of septations or mass, and same-day ERCP were not predictors of complications. CONCLUSIONS: EUS-guided pancreatic cyst aspiration carries a low complication rate similar to that reported for solid pancreatic lesions. No patient or cyst characteristics appear to be predictive of adverse events.