Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment.

BACKGROUND & AIMS: Wireless capsule endoscopy provides an opportunity to study the macroscopic features in celiac disease by providing a magnified view of the intestinal mucosa. In this study, we evaluated the following: (1) the distribution of atrophy in untreated celiac disease, (2) the correlation between extent of changes and clinical manifestations, (3) the accuracy and interobserver agreement of wireless capsule endoscopy assessment, and (4) the effect of gluten withdrawal. METHODS: Thirty-eight consecutive patients with untreated biopsy-proven celiac disease underwent wireless capsule endoscopy. Each subject was invited to undergo repeat testing after at least 6 months of gluten withdrawal. The video images of each patient were reviewed independently by 2 investigators. RESULTS: Thirty-five (92%) subjects had visible atrophy detected by capsule endoscopy. Twenty-two (59%) subjects showed an extensive enteropathy, 12 (32%) had enteropathy limited to the duodenum, and only 1 had a jejunal enteropathy. No association was shown between the extent of the lesion and clinical manifestations. Capsule endoscopy had a better overall sensitivity for the detection of atrophy as compared with upper endoscopy (92% vs 55%, P = .0005), with a specificity of 100%. The overall interobserver agreement for the 2 reviewers was relatively high (% total agreement, 86.5%). After gluten withdrawal, the extent and the pattern of atrophy improved both qualitatively and quantitatively. CONCLUSIONS: Celiac disease affects a highly variable portion of the small intestine starting at the duodenum. The extent of visible enteropathy does not explain differences in clinical presentation. Most subjects with visually detected villous atrophy showed a clinically significant improvement after gluten withdrawal.

Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures.

BACKGROUND AND AIMS: Standard techniques for evaluating bile duct strictures have poor sensitivity for detection of malignancy. Newer imaging modalities, such as intraductal ultrasound (IDUS), and advanced cytologic techniques, such as digital image analysis (DIA) and fluorescence in situ hybridization (FISH), identify chromosomal abnormalities, and may improve sensitivity while maintaining high specificity. Our aim was to prospectively evaluate the accuracy of these techniques in patients with indeterminate biliary strictures. METHODS: Cholangiography, routine cytology (RC), intraductal biopsy, DIA, FISH, and IDUS were performed in 86 patients with indeterminate biliary strictures. Patients were stratified based on the presence or absence of primary sclerosing cholangitis (PSC). RESULTS: RC provided low sensitivity (7-33%) but high specificity (95-100%) for PSC and non-PSC patients. The composite DIA/FISH results (when considering trisomy-7 [Tri-7] as a marker of benign disease) yielded a 100% specificity and increased sensitivity one- to fivefold in PSC patients versus RC, and two- to fivefold in patients without PSC, depending on how suspicious cytology results were interpreted. For the most difficult-to-manage patients with negative cytology and histology who were later proven to have malignancy (N = 21), DIA, FISH, composite DIA/FISH, and IDUS were able to predict malignant diagnoses in 14%, 62%, 67%, and 86%, respectively. CONCLUSIONS: DIA, FISH, and IDUS enhance the accuracy of standard techniques in evaluation of indeterminate bile duct strictures, allowing diagnosis of malignancy in a substantial number of patients with false-negative cytology and histology. These findings support the routine use of these newer diagnostic modalities in patients with indeterminate biliary strictures.

A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures.

BACKGROUND AND AIMS: The aim of the study was to examine whether endoscopic intralesional corticosteroid injection into recalcitrant peptic esophageal strictures reduces the need for repeat stricture dilation. METHODS: Patients with a peptic esophageal stricture and recurrent dysphagia having had at least one dilation in the preceding 18 months were enrolled in a prospective randomized, double-blind study comparing steroid and sham injection. After endoscopic confirmation of recurrent stricture, patients were randomized to receive either 0.5 cc/quadrant triamcinolone (40 mg/cc) or sham injection into the stricture followed by balloon dilation of the stricture. Patients were stratified by the number of dilations required in the preceding 18 months, severity of dysphagia, the presence of esophagitis, stricture severity, and prior therapy with a proton-pump inhibitor. Patients and their physicians were blinded to the type of intervention received. Baseline dysphagia questionnaires were completed. Post-procedurally all patients were placed on a standardized proton-pump inhibitor regimen and standardized telephone follow-up questionnaires were completed at 1 wk and at 1, 3, 6, 9, and 12 months. The original sample-size calculation of 60 patients could not be met in a timely fashion because of a low incidence of recalcitrant peptic stricture patients. RESULTS: A total of 30 patients were enrolled, 15 in the steroid group (10 men, mean age 66 yr) and 15 in the sham group (11 M, mean age 67 yr). Patients were followed for 1 yr, unless they underwent an antireflux operation or died. Two patients, one per group, died of non-esophageal causes at 1 and 12 months. Four patients had fundoplication, two in each group, unrelated to stricture or dysphagia. Two patients in the steroid group (13%) and nine in the sham group (60%) required repeat dilation (p= 0.011). CONCLUSIONS: In patients with recalcitrant peptic esophageal stricture, steroid injection into the stricture combined with acid suppression significantly diminishes both the need for repeat dilation and the average time to repeat dilation compared to sham injection and acid suppression alone.

Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma.

BACKGROUND: Photodynamic therapy (PDT) has demonstrated promise in the palliative treatment of advanced cholangiocarcinoma. The aim of this pilot study was to assess the outcome in patients with non-resectable cholangiocarcinoma following endoscopic application of PDT directly into the biliary tract. METHODS: In patients with advanced cholangiocarcinoma, endoscopic retrograde cholangiopancreatography (ERCP) was performed to define the proximal and distal extent of intraductal tumor. Sodium porfimer was administered intravenously to all patients. Forty-eight hours later, a commercially available cylindrical diffusing laser fiber (1-2.5 cm in length, OptiGuide) designed for esophageal use was advanced across the biliary strictures. Laser light was applied at a power of 400 mW/cm fiber for a total energy of 180 J/cm(2) using an argon-pumped tunable dye laser. Patients received endoscopic PDT every 3 months provided they maintained a favorable performance status. Plastic biliary stents were replaced immediately following light application and were maintained in all patients. RESULTS: Using a preloaded catheter, adequate positioning of the laser fiber was achieved in all patients. Eight patients with advanced cholangiocarcinoma received a total of 19 PDT treatments, range 1-5 treatments/patient. All eight patients were followed until death; mean follow-up was 9.8 months. Median survival from the date of the first PDT treatment was 276 days, which compares favorably with published series that have reported median survival times between 45 and 127 days for patients with bismuth type III and IV tumors treated with stenting alone. CONCLUSIONS: Endoscopic application of PDT demonstrates promise in prolonging survival in patients with advanced cholangiocarcinoma. Additional randomized clinical trials using commercially available fibers are needed to fully evaluate both the optimum frequency and treatment interval of endoscopic PDT in the management of advanced cholangiocarcinoma.

Comparison of direct percutaneous endoscopic jejunostomy and PEG with jejunal extension.

BACKGROUND: Jejunostomy tubes can be placed endoscopically by means of percutaneous gastrostomy with jejunal extension (PEG-J) or by direct percutaneous jejunostomy. These 2 techniques were retrospectively compared in patients requiring long-term jejunal feeding. METHOD: An endoscopy database was used to identify all patients who underwent endoscopic jejunal feeding tube placement from January 1996 to May 2001. Patients with a history of upper GI surgery were excluded. There were 56 patients with a direct percutaneous jejunostomy and 49 with a percutaneous gastrostomy with jejunal extension. Patients in the direct percutaneous jejunostomy group received a 20F direct jejunostomy tube; a 20F PEG tube with a 9F jejunal extension was used in the percutaneous gastrostomy with jejunal extension group. Medical records for the period of 6 months after establishment of jejunal access were reviewed. Complications and need for further endoscopic intervention within this time frame were recorded. The duration of feeding tube patency (number of days from established jejunal access to first endoscopic reintervention) was compared for both groups. RESULTS: Feeding tube patency was significantly longer in patients who had a direct percutaneous jejunostomy compared with those with a percutaneous gastrostomy with jejunal extension. Within the 6-month period, 5 patients with a direct percutaneous jejunostomy required endoscopic reintervention for tube dysfunction compared with 19 patients who had a percutaneous gastrostomy with jejunal extension (p < 0.0001). CONCLUSIONS: For patients who require long-term jejunal feeding, a direct percutaneous jejunostomy with a 20F tube provides more stable jejunal access compared with a percutaneous gastrostomy with jejunal extension with a 9F extension and has a lower associated rate of endoscopic reintervention.

Efficacy of colonic submucosal saline solution injection for the reduction of iatrogenic thermal injury.

BACKGROUND: Submucosal saline solution injection may limit the depth of thermal injury to the gut wall by acting as a heat-sink and by increasing the distance between burn and serosa. The aim of this study was to determine the effect of submucosal saline solution injection on depth of colonic thermal injury produced by commonly used endoscopic thermal modalities. METHODS: Longitudinal colotomy incisions were made on the antimesenteric colonic border of anesthetized swine. Lesions were made by using a bipolar device (20 W, 2 seconds), heat probe (30 J); monopolar contact with hot biopsy forceps (20 W, 2 seconds), and monopolar noncontact with argon plasma coagulation (45 W, 3 seconds). Ten or more lesions were created with each device. Lesions were made with or without prior submucosal injection of 2 mL of normal saline solution. After 24 hours the lesions were excised for histologic analysis. Injury was assessed in relation to the severity of damage to the deep (longitudinal) muscle layer. RESULTS: The proportions of control lesions (without submucosal saline solution injection) in which deep injury was evident were as follows: argon plasma coagulation, 86%; hot biopsy forceps, 64%; heat probe, 50%; bipolar device, 18%. Submucosal saline solution injection significantly reduced the proportions of lesions with deep injury for argon plasma coagulation (p = 0.009) and heat probe (p = 0.03), but not hot biopsy forceps or bipolar device (argon plasma coagulation, 86% to 21%; heat probe, 50% to 0%; hot biopsy forceps, 64% to 50%; bipolar device, 18% to 9%). CONCLUSIONS: At equivalent energy outputs, the bipolar device results in less deep injury than the monopolar or heat probe. Submucosal saline solution injection reduced injury to the muscularis propria caused by both heat probe and argon plasma coagulation, but not hot biopsy forceps. Despite submucosal saline solution injection, caution should be exercised when using prolonged monopolar cautery.

Development of a swine model for benign stenosis of the bile duct by endoscopic application of intraluminal thermal injury.

BACKGROUND: A simple animal model is desirable for the study of endoscopic therapies used in the management of biliary strictures. The aim of this study was to identify a method for inducing benign biliary stenoses in a porcine model by using endoscopic techniques. METHODS: Endoscopic retrograde cholangiography was performed in 9 swine. Intraluminal injury was applied to the common hepatic duct with graded applications of either a heat probe or a multipolar probe. Cholangiography was repeated at 7-day intervals. If a stricture was not identified by 28 days, injury was created at another site in the common hepatic duct by using a higher energy dose. After a stricture was identified, the animal was killed and bile duct samples were obtained for histopathologic evaluation. RESULTS: Thirteen thermal injuries were created in the 9 animals. Six of 7 heat probe treatments and 1 of 6 multipolar probe treatments resulted in a stricture (p = 0.025, Fisher exact test). Applications of the heat probe at 10 or 15 J produced a stricture in 6 of 6 cases. All strictures were indistinguishable histopathologically from benign strictures in humans. CONCLUSIONS: The application of intraluminal thermal injury with a heat probe results in a reproducible animal model of benign biliary stenosis.

A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures.

BACKGROUND & AIMS: Digital image analysis (DIA) allows quantification of nuclear DNA content and may help distinguish benign and malignant strictures of the biliary tract. METHODS: One hundred ten consecutive patients undergoing endoscopic retrograde cholangiography for suspicious biliary tract strictures were enrolled in a prospective study comparing the accuracy of DIA and routine cytology (RC). Standard brush cytology sampling was performed twice by using 2 cytology brushes per patient. Both brushes were fixed in a single-specimen vial. Each specimen was formed into 1 pellet, and the sample was equally divided for evaluation by DIA and RC. DNA histograms were generated for ploidy analysis. The DIA criterion for malignancy was demonstration of aneuploidy. RESULTS: Two patients had inadequate samples obtained for DIA analysis, 7 benign patients were excluded because of inadequate follow-up of less than 75 days, and 1 patient was lost to follow-up to clarify malignant versus benign disease. Of the remaining 100 patients, 56 strictures were malignant and 44 were benign. The sensitivities of DIA and RC were 39.3% and 17.9%, respectively (P = 0.014). The specificities of DIA and RC were 77.3% and 97.7%, respectively (P = 0.003). The accuracy of DIA (56.0%) was equivalent to RC (53.0%). CONCLUSIONS: DIA is a valuable adjunct to RC for detecting malignant strictures of the biliary tract.