Gerard Isenberg

High-resolution endoscopic imaging of the GI tract using optical coherence tomography.

BACKGROUND Optical coherence tomography (OCT) has demonstrated the microscopic structure of the gastrointestinal (GI) tract mucosa and submucosa in vitro. We evaluated a prototype OCT system and assessed the feasibility of OCT in the human GI tract. METHODS The 2.4 mm diameter prototype OCT probe, inserted through an endoscope, provides a 360-degree radial scan. Images (6.7 frames/sec) are displayed on a television monitor. Tissue contact is not required. In patients undergoing elective endoscopy, OCT images were obtained of normal mucosa (confirmed by biopsy). RESULTS Seventy-two sites were imaged (38 patients): esophagus (21), stomach (12), duodenum (11), terminal ileum (4), colon (15), and rectum (9). Varying the distance between the probe and the mucosal surface produced images of the GI wall of varying depth. When held about 1 mm above the mucosal surface, the images consisted of mucosal structures such as colonic crypts, gastric pits, and duodenal villi. With the probe held against the wall, the OCT image comprised several layers interpreted as mucosa, muscularis mucosae, and submucosa. Structures including blood vessels were evident within the submucosa. A probe with a 0.5 mm working distance to the focal point provided the best images. Reducing the frame rate to 4.0 per second facilitated image interpretation. CONCLUSIONS OCT is feasible in the human GI tract and provides interpretable high-resolution images of mucosa and submucosa.

Computer-aided diagnosis of dysplasia in Barrett's esophagus using endoscopic optical coherence tomography.

Barretts esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem over the last two decades. Because of the widespread use of endoscopy, BE is being recognized increasingly in all Western countries. In clinical trials of endoscopic optical coherence tomography (EOCT), we defined certain image features that appear to be characteristic of precancerous (dysplastic) mucosa: decreased scattering and disorganization in the microscopic morphology. The objective of the present work is to develop computer-aided diagnosis (CAD) algorithms that aid the detection of dysplasia in BE. The image dataset used in the present study was derived from a total of 405 EOCT images (13 patients) that were paired with highly correlated histologic sections of corresponding biopsies. Of these, 106 images were included in the study. The CAD algorithm used was based on a standard texture analysis method (center-symmetric auto-correlation). Using histology as the reference standard, this CAD algorithm had a sensitivity of 82%, specificity of 74%, and accuracy of 83%. CAD has the potential to quantify and standardize the diagnosis of dysplasia and allows high throughput image evaluation for EOCT screening applications. With further refinements, CAD could also improve the accuracy of EOCT identification of dysplasia in BE.

Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation

BACKGROUND Endoscopic ultrasound (EUS) is established as the most accurate method currently available for determining the depth of primary cancer invasion (T stage). Standard EUS criteria may not be accurate in assessing depth of cancer invasion and nodal status after patients have received chemotherapy or radiotherapy. METHODS We conducted a prospective study to determine whether EUS estimation of tumor size could be used to assess response to preoperative chemoradiation. Using EUS, TNM stage was assessed in 31 patients (22 men, 9 women; mean age 62 years) with cancer of esophagus or cardia (19 adenocarcinoma, 12 squamous cell cancer) before initiation of combined radiation and 5-fluorouracil/cisplatin (and/or carboplatinum) chemotherapy. The cross-sectional area of the tumor in the transverse plane at the location where the tumor had maximal thickness was calculated to estimate tumor size. EUS staging and measurement of maximal cross-sectional area were repeated at completion of chemoradiation just before surgery. Response to preoperative chemoradiation was defined as 50% reduction in maximal cross-sectional area. Surgical staging was compared between responders and nonresponders. RESULTS Eight patients who did not undergo surgery were excluded from analysis. EUST stage in the remaining 23 patients before therapy was as follows: 3 T2, 16 T3, and 4 T4. After chemoradiation, EUS T staging was changed in 6 patients (3 T4 downstaged to T3, 2 T3 downstaged to T2, and 1 T3 downstaged to T1). At surgical pathological examination, 3 patients had no residual tumor in the esophagus (T0), 5 had T1, 3 had T2, 10 had T3, and 2 had T4 tumors. EUS T staging accuracy after adjuvant therapy was only 43%. Maximal cross-sectional area decreased from a mean of 5.5 +/- 2.4 to 1.6 +/- 0.9 cm2 in responders, whereas maximal cross-sectional area went from 7.0 +/- 3.0 to 5.4 +/- 2.2 cm2 in nonresponders (p = 0.009). Ten of thirteen patients with at least a 50% reduction in maximal cross-sectional area (responders) had T0, T1, or T2 tumors at surgery, whereas 9 of 10 nonresponders had T3 or T4 tumors at surgery (p = 0.001). CONCLUSIONS (1) Standard EUS staging criteria are not accurate after neoadjuvant chemoradiation, (2) reduction in maximal cross-sectional area of tumor appears to be a more useful measure for assessing response of esophageal cancer to preoperative chemoradiation, and (3) responders have an increased likelihood of downstaging at surgery than nonresponders.

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.

Long-term follow-up of patients with clinically indeterminate suspicion of pancreatic cancer and normal EUS

BACKGROUND EUS often is performed because of a clinical suspicion of pancreatic cancer when the results of other noninvasive diagnostic tests are indeterminate. The aim of this study was to determine the true negative predictive value of a normal EUS in a cohort of patients with an indeterminate suspicion of pancreatic cancer by obtaining long-term follow-up information. METHODS Patients referred for EUS of the pancreas for the following indications were identified: elevated carbohydrate-associated antigen (CA 19-9) without other definitive evidence of pancreatic cancer, subtle abnormalities on CT of the pancreas, and unexplained abdominal pain and/or weight loss. Endoscopy procedure reports, as well as inpatient and outpatient records were obtained. In addition, referring physicians, as well as patients, were contacted to acquire adequate follow-up information. RESULTS A total of 80 patients were included in the study. Follow-up of at least 6 months was obtained for 76 (95%) patients (mean follow-up 23.9 months). No patient with a normal EUS of the pancreas developed pancreatic cancer or required pancreatic surgery during the follow-up period. One patient in whom a diagnosis of chronic pancreatitis was made by EUS subsequently was found to have pancreatic cancer at surgery. CONCLUSIONS A normal EUS of the pancreas in the setting of subtle radiologic findings, serologic abnormalities, and/or nonspecific symptoms definitively rules out the presence of pancreatic cancer.

Endoscopic retrograde cholangiopancreatography in children and adolescents.

Objectives Endoscopic retrograde cholangiopancreatography (ERCP) is becoming a more frequently used diagnostic and therapeutic tool in children. We sought to determine the indications, feasibility, safety, and effect on patient management of ERCP in pediatric patients of varying age. Methods All ERCPs performed during a 4-year period in patients aged 18 years or less at an academic hospital were retrospectively reviewed. The indications, type of anesthesia administered, type of duodenoscope used, diagnostic findings, therapeutic interventions, complication rate, and effect on management were compared between children (age 0–12 years) and adolescents (age 13–18 years). Results A total of 53 procedures were performed in 43 patients whose median age was 13.5 years. ERCP was successful in 50 of 53 cases (94%) with a complication rate of 6%. Endoscopic therapy was provided in 24 of 53 cases (45%). Compared with adolescents (n = 28), children (n = 25) were more likely to receive general anesthesia (96% vs. 29%;P < 0.001) and undergo ERCP with a pediatric duodenoscope (0% vs. 40%). ERCP affected management in 73% of cases, equally in both groups. Conclusion ERCP is a successful and safe diagnostic and therapeutic modality in a variety of pancreatobiliary disorders that directly affects management in children of all ages.

Prospective evaluation of an over-the-wire catheter US probe

BACKGROUND Pancreaticobiliary strictures identified at endoscopic retrograde cholangiopancreatography (ERCP) can be evaluated by intraductal ultrasonography (US). Two major difficulties are that sphincterotomy may be required and the stricture may not be traversable. We prospectively evaluated the ease and success of intraductal US using a new over-the-wire catheter US probe. METHODS Biliary or pancreatic strictures discovered at ERCP were imaged with the new probe. Intraductal US performance times, image clarity, imaging depth and technical ease were measured. RESULTS Twenty-one patients with a variety of inflammatory and malignant pancreaticobiliary lesions were studied. Thirteen of the 16 (81%) masses imaged by intraductal US were 10 mm or less in diameter. Sphincterotomy was not required. All strictures traversed by a guidewire were imaged. The sphincter of Oddi was successfully imaged in all patients with intact normal sphincters. Performance of intraductal US was rated as technically easy in all cases and image clarity was rated as good or very good in 15 of 21 (71%) cases. CONCLUSIONS The new over-the-wire catheter US probe facilitates intraductal US. Sphincterotomy is avoided and strictures are successfully traversed. This probe makes it possible to image the sphincter of Oddi.

Image analysis for classification of dysplasia in Barrett's esophagus using endoscopic optical coherence tomography.

Barrett’s esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem. Endoscopic optical coherence tomography is a microscopic sub-surface imaging technology that has been shown to differentiate tissue layers of the gastrointestinal wall and identify dysplasia in the mucosa, and is proposed as a surveillance tool to aid in management of BE. In this work a computer-aided diagnosis (CAD) system has been demonstrated for classification of dysplasia in Barrett’s esophagus using EOCT. The system is composed of four modules: region of interest segmentation, dysplasia-related image feature extraction, feature selection, and site classification and validation. Multiple feature extraction and classification methods were evaluated and the process of developing the CAD system is described in detail. Use of multiple EOCT images to classify a single site was also investigated. A total of 96 EOCT image-biopsy pairs (63 non-dysplastic, 26 low-grade and 7 high-grade dysplastic biopsy sites) from a previously described clinical study were analyzed using the CAD system, yielding an accuracy of 84% for classification of non-dysplastic vs. dysplastic BE tissue. The results motivate continued development of CAD to potentially enable EOCT surveillance of large surface areas of Barrett’s mucosa to identify dysplasia.

Variability in measurements of pancreatic cyst size among EUS, CT, and magnetic resonance imaging modalities.

BACKGROUND Cyst size is an important factor in the management of pancreatic cysts, both in predicting the need for surgery and the frequency of follow-up. OBJECTIVE To determine agreement and precision of EUS, CT, and magnetic resonance imaging (MRI) modalities in the evaluation of pancreatic cyst diameter. DESIGN Retrospective chart review. SETTING Tertiary-care center, January 2000 to June 2009. PATIENTS This study involved 175 patients presenting for EUS evaluation of pancreatic cysts, with size measured by at least two of the aforementioned imaging studies within a 90-day period. MAIN OUTCOME MEASUREMENTS Largest cyst diameter from EUS, CT, MRI/MRCP, and surgical pathology. RESULTS A total of 175 patients underwent EUS. Seventy-three had CT plus EUS, 33 had MRI/MRCP plus EUS, 23 had MRI/MRCP plus CT, and 15 had all imaging studies, occurring within 90 days of each other. Median size differences between studies: EUS and CT (ie, absolute value of size determined by EUS minus size determined by CT) = 4 mm (range 0-25 mm), EUS and MRI = 4 mm (range 0-17 mm), CT and MRI = 3 mm (range 2-20 mm). Median size differences for surgical pathology specimens compared with results of 12 EUS, 13 CT, and 8 MRI/MRCP studies were as follows: EUS and pathology = 9.5 mm (range 0-20 mm), CT and pathology = 5 mm (range 0-21 mm), MRI and pathology = 5.5 mm (range 2-44 mm). LIMITATIONS Interobserver variability and small sample of surgical pathology cysts. CONCLUSION There is considerable variation in size estimates of pancreatic cysts by different imaging modalities, which practitioners should take into account when making management decisions. Use of a single imaging modality is recommended during follow-up. The precision of imaging studies for measuring pancreatic cysts must be prospectively defined if change in size is to be reliably used for clinical management.

Small bowel capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter defibrillators: Outcome analysis using telemetry review.

AIM To determine if there were any interactions between cardiac devices and small bowel capsules secondary to electromagnetic interference (EMI) in patients who have undergone small bowel capsule endoscopy (SBCE). METHODS Authors conducted a chart review of 20 patients with a cardiac pacemaker (CP) or implantable cardioverter defibrillator (ICD) who underwent continuous electrocardiographic monitoring during their SBCE from 2003-2008. authors searched for unexplained electrocardiogram (ECG) findings, changes in CP and ICD set parameters, any abnormality in transmitted capsule data, and adverse clinical events. RESULTS There were no adverse events or hemodynamically significant arrhythmias reported. CP and ICD set parameters were preserved. The majority of ECG abnormalities were also found in pre- or post- SBCE ECG tracings and the CP behavior during arrhythmias appeared appropriate. Two patients seemed to have episodes of undersensing by the CP. However, similar findings were documented in ECGs taken outside the time frame of the SBCE. One patient was observed to have a low signal encountered from the capsule resulting in lack of localization, but no images were lost. CONCLUSION Capsule-induced EMI remains a possibility but is unlikely to be clinically important. CP-induced interference of SBCE is also possible, but is infrequent and does not result in loss of images transmitted by the capsule.