Michael D. Saunders

Acute pancreatitis after EUS-guided FNA of solid pancreatic masses: a pooled analysis from EUS centers in the United States

BACKGROUND The aim of this study was to determine the frequency and the severity of pancreatitis after EUS-guided FNA of solid pancreatic masses. A survey of centers that offer training in EUS in the United States was conducted. METHODS A list of centers in which training in EUS is offered was obtained from the Web site of the American Society for Gastrointestinal Endoscopy. Designated program directors were contacted via e-mail. The information requested included the number of EUS-guided FNA procedures performed for solid pancreatic masses, the number of cases of post-procedure pancreatitis, and the method for tracking complications. For each episode of pancreatitis, technical details were obtained about the procedure, including the location of the mass, the type of fine needle used, the number of needle passes, and the nature of the lesion. RESULTS Nineteen of the 27 programs contacted returned the questionnaire (70%). In total, 4909 EUS-guided FNAs of solid pancreatic masses were performed in these 19 centers over a mean of 4 years (range 11 months to 9 years). Pancreatitis occurred after 14 (0.29%): 95% CI[0.16, 0.48] procedures. At two centers in which data on complications were prospectively collected, the frequency of acute pancreatitis was 0.64%, suggesting that the frequency of pancreatitis in the retrospective cohort (0.26%) was under-reported (p=0.22). The odds that cases of pancreatitis would be reported were 2.45 greater for the prospective compared with the retrospective cohort (95% CI[0.55, 10.98]). The median duration of hospitalization for treatment of pancreatitis was 3 days (range 1-21 days). The pancreatitis was classified as mild in 10 cases, moderate in 3, and severe in one; one death (proximate cause, pulmonary embolism) occurred after the development of pancreatitis in a patient with multiple comorbid conditions. CONCLUSIONS EUS-guided FNA of solid pancreatic masses is infrequently associated with acute pancreatitis. The procedure appears to be safe when performed by experienced endosonographers. The frequency of post EUS-guided FNA pancreatitis may be underestimated by retrospective analysis.

A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses

BACKGROUND The purpose of this study is to prospectively evaluate the performance characteristics of endoscopy and EUS in the diagnosis of GI subepithelial masses. METHODS A total of 100 consecutive patients referred for the evaluation of a suspected GI subepithelial lesion were prospectively studied with endoscopy followed by EUS. Size, color, mobility, location (intramural or extramural), consistency (solid, cystic, or vascular), and presumptive diagnosis were recorded at the time of endoscopy. EUS then was performed, and size, echogenicity, location, and presumptive diagnosis were determined. RESULTS A total of 100 subepithelial lesions were evaluated. Endoscopy had 98% sensitivity and 64% specificity in identifying intramural lesions. Size measurement by endoscopy correlated with size measurement by EUS (r = 0.88). Histology was obtained in 23 cases, with the presumptive EUS diagnosis correct in only 48% of cases. Most incorrect EUS diagnoses occurred with hypoechoic 3rd and 4th layer masses. CONCLUSIONS Endoscopy has high sensitivity but low specificity in identifying the location (intramural or extramural) of subepithelial lesions. In addition, EUS imaging alone is insufficient to accurately diagnose 3rd and 4th layer hypoechoic masses, and histologic confirmation should be obtained whenever possible.

A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance

BACKGROUND AND STUDY AIMS Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) of pancreatic cystic lesions (PCL) is flawed by inadequate diagnostic yield. Needle-based confocal laser endomicroscopy (nCLE) utilizes a sub-millimeter probe that is compatible with an EUS needle and enables real-time imaging with microscopic detail of PCL. The aims of the In vivo nCLE Study in the Pancreas with Endosonography of Cystic Tumors (INSPECT) pilot study were to assess both the diagnostic potential of nCLE in differentiating cyst types and the safety of the technique. PATIENTS AND METHODS Eight referral centers performed nCLE in patients with PCL. Stage 1 defined descriptive terms for structures visualized by an off-line, unblinded consensus review. Cases were reviewed with a gastrointestinal pathologist to identify correlations between histology and nCLE. Stage 2 assessed whether the specific criteria defined in Stage 1 could identify pancreatic cystic neoplasms (PCN) including intraductal papillary mucinous neoplasms, mucinous cystic adenoma, or adenocarcinoma in an off-line blinded consensus review. RESULTS A total of 66 patients underwent nCLE imaging and images were available for 65, 8 of which were subsequently excluded due to insufficient information for consensus reference diagnosis. The presence of epithelial villous structures based on nCLE was associated with PCN (P=0.004) and provided a sensitivity of 59%, specificity of 100%, positive predictive value of 100 %, and negative predictive value of 50%. The overall complication rate was 9% and included pancreatitis (1 mild case, 1 moderate case), transient abdominal pain (n=1), and intracystic bleeding not requiring any further measures (n=3). CONCLUSIONS These preliminary data suggested that nCLE has a high specificity in the detection of PCN, but may be limited by a low sensitivity. The safety of nCLE requires further evaluation.

Multicenter, randomized, controlled trial of confocal laser endomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barrett's esophagus.

BACKGROUND Endoscopic ablation is an accepted standard for neoplasia in Barretts esophagus (BE). Eradication of all glandular mucosa in the distal esophagus cannot be reliably determined at endoscopy. OBJECTIVE To assess if use of probe-based confocal laser endomicroscopy (pCLE) in addition to high-definition white light (HDWL) could aid in determination of residual BE. DESIGN Prospective, multicenter, randomized, clinical trial. SETTING Academic medical centers. PATIENTS Patients with Barretts esophagus undergoing ablation. INTERVENTION After an initial attempt at ablation, patients were followed-up either with HDWL endoscopy or HDWL plus pCLE, with treatment of residual metaplasia or neoplasia based on endoscopic findings and pCLE used to avoid overtreatment. MAIN OUTCOME MEASUREMENTS The proportion of optimally treated patients, defined as those with residual BE who were treated and had complete ablation plus those without BE who were not treated and had no evidence of disease at follow-up. RESULTS The study was halted at the planned interim analysis based on a priori criteria. After enrollment was halted, all patients who had been randomized were followed to study completion. Among the 119 patients with follow-up, there was no difference in the proportion of patients achieving optimal outcomes in the two groups (15/57, 26% for HDWL; 17/62, 27% with HDWL + pCLE). Other outcomes were similar in the two groups. LIMITATIONS The study was closed after the interim analysis due to low conditional power resulting from lack of difference between groups as well as higher-than-expected residual Barretts esophagus in both arms. CONCLUSION This study yields no evidence that the addition of pCLE to HDWL imaging for detection of residual Barretts esophagus or neoplasia can provide improved treatment.

Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease after autologous hematopoietic cell transplantation.

BACKGROUND Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation. METHODS We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease. RESULTS Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987–1997: incidence, causes, and outcome

Hepatotoxicity associated with 6-thioguanine therapy for Crohn's disease

6-Thioguanine (6-TG) is a thiopurine analogue that is closely related to 6-mercaptopurine (6-MP) and azathioprine (AZA). These agents have potent cytotoxic and immunomodulatory effects and are useful in the treatment of a variety of conditions, including inflammatory bowel disease. Both 6-MP and AZA are widely used and are known to cause hepatotoxicity in a proportion of patients. 6-Thioguanine is being increasingly used in the treatment of inflammatory bowel disease but has not been reported to cause liver injury in this context. We describe a case of significant elevation of serum transaminases in a patient treated with 6-TG for a flare of Crohns disease. We believe the temporal association of the abnormal liver enzymes in this patient, in the absence of other offending agents, argues strongly in favor of 6-TG as a cause of liver enzyme abnormalities. This case highlights the need to monitor liver enzymes in patients treated with 6-TG and identifies the need for additional research focused on the mechanism of thiopurine-induced hepatic injury.

Barrett's esophagus: endoscopic diagnosis.

This collection of summaries on endoscopic diagnosis of Barretts esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra‐short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Randomized non-inferiority trial comparing diagnostic yield of cytopathologist-guided versus seven passes for endoscopic ultrasound-guided fine-needle aspiration of pancreatic masses: Randomized trial EUS-FNA pancreatic mass

To improve diagnostic yield of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) in solid pancreatic lesions, on‐site cytology review has been recommended. Because this is not widely available throughout the world, the aim of the present study was to compare the diagnostic yield of EUS‐FNA carried out with rapid on‐site evaluation (ROSE) versus seven FNA passes without ROSE in pancreatic masses.

Scanning fiber endoscopy: a novel platform for cholangioscopy.

Indeterminate pancreaticobiliary strictures remain a difficult diagnostic dilemma with currently available endoscopic imaging. Currently available pancreaticobiliary endoscopic systems have improved the sensitivity of directed biopsy; however, they are limited by image quality. We present scanning fiber endoscopy (SFE) as a novel platform for improving diagnostic accuracy. This endoscopic platform works through a standard side-viewing endoscope. SFE works by using a singlemode optical fiber whose distal tip is resonantly scanned in a spiral pattern. This fiber traces up to 300 enlarging spirals to generate a video feed. Because there is no direct pixel to fiber input, there are no “honeycombed” or non-imaging areas in view. Additionally, the decreased number of fibers allows for a highly flexible shaft with an improved bending radius. Here, we present 3 cases in which SFE was used in human participants as part of a prospective internal review board– approved protocol: 2 benign biliary strictures and 1 cholangiocarcinoma arising from a biliary intraductal