Brenda J. Hoffman

Radiofrequency Ablation in Barrett's Esophagus with Dysplasia

BACKGROUND Barretts esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barretts esophagus and decrease the rate of neoplastic progression. METHODS In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barretts esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barretts esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS In patients with dysplastic Barretts esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion.

BACKGROUND The purpose of this study was to re-evaluate echo features of lymph nodes during endoscopic ultrasound and assess the utility of these echo features and endoscopic ultrasound-guided fine-needle aspiration in predicting malignant lymph node invasion. METHODS Thirty-five lymph nodes in 25 patients with lung, esophageal, and pancreatic cancer were evaluated by endoscopic ultrasound. Endoscopic ultrasound examinations were performed with a radial scanning echoendoscope. Confirmation of benign lymph nodes was obtained by surgical resection while malignant lymph nodes were confirmed by real-time endoscopic ultrasound-guided fine-needle aspiration with a linear array echoendoscope. RESULTS Nineteen benign lymph nodes and 16 malignant lymph nodes in the mediastinum, celiac axis, and the peripancreatic area were included in the study. The following echo features were compared between benign and malignant lymph nodes: size greater than 1 cm, hypoechoic, distinct margins, and round shape. No single feature independently predicted malignant invasion. When all four of the above features were present in the same lymph node, the accuracy for predicting malignant invasion was 80%. However, all four features of malignant involvement were present in only 25% (4 of 16) of malignant lymph nodes. Our study also suggests that the above echo features may be a less reliable predictor of malignant invasion in pulmonary malignancies when compared to gastrointestinal cancers. Endoscopic ultrasound-guided fine-needle aspiration of lymph nodes in 22 patients revealed malignant lymph node invasion in 16 and benign cells in 6 patients. CONCLUSION Endoscopic ultrasound-guided fine-needle aspiration is an important adjunct for accurate lymph node assessment for malignancy.

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

BACKGROUND & AIMS Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barretts esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Quality indicators for colonoscopy.

Colonoscopy is widely used for the diagnosis and treatment of colonic disorders. Properly performed, colonoscopy is generally safe, accurate, and well tolerated by most patients. Visualization of the mucosa of the entire large intestine and distal terminal ileum is usually possible at colonoscopy. In patients with chronic diarrhea, biopsy specimens can help diagnose the underlying condition. Polyps can be identified and removed during colonoscopy, thereby reducing the risk of colon cancer. Colonoscopy is the preferred method to evaluate the colon in most adult patients with bowel symptoms, iron deficiency anemia, abnormal radiographic studies of the colon, positive colorectal cancer screening tests, postpolypectomy and postcancer resection surveillance, surveillance in inflammatory bowel disease, and in those with suspected masses. The use of colonoscopy has become accepted as the most effective method of screening the colon for neoplasia in patients over the age of 50 years and in younger patients at increased risk (1). The effectiveness of colonoscopy in reducing colon cancer incidence depends on adequate visualization of the entire colon, diligence in examining the mucosa, and patient acceptance of the procedure. Preparation quality affects the ability to perform a complete examination, the duration the procedure, and the need to cancel or reschedule procedures (2, 3). Ineffective preparation is a major contributor to costs (4). Longer withdrawal times have been demonstrated to improve polyp detection rates, (5–7) and conversely, rapid withdrawal may miss lesions and reduce the effectiveness of colon cancer prevention by colonoscopy. The miss rates of colonoscopy for large (≥1 cm) adenomas may be higher than previously thought (8, 9) Thus, careful examinations are necessary to optimize the effectiveness of recommended intervals between screening and surveillance examinations. Finally, technical expertise will help prevent complications that can offset any cost benefit ratio gained by removing neoplastic lesions. The following quality indicators have been selected to establish competence in performing colonoscopy and help define areas for continuous quality improvement. The levels of evidence supporting these quality indicators were graded according to Table 1. PREPROCEDURE

Endoscopic ultrasound with fine-needle aspiration in the Diagnosis and staging of lung cancer

BACKGROUND Esophageal endoscopic ultrasonographic (EUS) guidance for fine-needle aspiration (FNA) of mediastinal lymph nodes has been introduced only recently. The utility of EUS/FNA in diagnosing and staging bronchogenic carcinoma is unknown. METHODS After a thoracic computed tomographic scan, 27 patients with known or suspected lung cancer underwent EUS. Accessible abnormal mediastinal lymph nodes were aspirated under EUS guidance. Patients with positive cytologic studies did not undergo further testing, whereas the remaining patients underwent mediastinal exploration. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for both chest computed tomography and EUS/FNA: RESULTS Twenty-two of 27 patients had mediastinal adenopathy by computed tomography scan. Sixteen patients had positive findings on EUS, 15 with positive FNA (10 non-small cell lung cancer; 5 small cell lung cancer) and 1 with T4 status. Fourteen patients with positive FNA had lymph nodes sampled at level 5, level 7, or both. Of 11 patients with negative EUS/FNA, 2 had positive findings at operation (sensitivity 89%). The diagnosis of lung cancer was established in 7 patients. CONCLUSIONS The results showed that EUS/FNA improves the accuracy of computed tomographic scan in the staging of lung cancer. By accessing lymph nodes at levels 5 and 7, EUS/FNA complements mediastinoscopy and is considered the staging modality of choice in these regions. Positive EUS/FNA can obviate the need for further invasive staging.

Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett's oesophagus: a prospective, international, randomised controlled trial

Background White light endoscopy with random biopsies is the standard for detection of intestinal metaplasia (IM) and neoplasia in patients with Barretts oesophagus (BO). Narrow band imaging (NBI) highlights surface patterns that correlate with IM and neoplasia in BO. Objective To compare high-definition white light (HD-WLE) and NBI for detection of IM and neoplasia in BO. Design International, randomised, crossover trial comparing HD-WLE and NBI. Patients referred for BO screening/surveillance at three tertiary referral centres were prospectively enrolled and randomised to HD-WLE or NBI followed by other procedures in 3–8 weeks. During HD-WLE, four quadrant biopsies every 2 cm, together with targeted biopsies of visible lesions (Seattle protocol), were obtained. During NBI examination, mucosal and vascular patterns were noted and targeted biopsies were obtained. All biopsies were read by a single expert gastrointestinal pathologist in a blinded fashion. Results 123 patients with BO (mean age 61; 93% male; 97% Caucasian) with mean circumferential and maximal extents of 1.8 and 3.6 cm, respectively, were enrolled. Both HD-WLE and NBI detected 104/113 (92%) patients with IM, but NBI required fewer biopsies per patient (3.6 vs 7.6, p<0.0001). NBI detected a higher proportion of areas with dysplasia (30% vs 21%, p=0.01). During examination with NBI, all areas of high-grade dysplasia and cancer had an irregular mucosal or vascular pattern. Conclusions NBI targeted biopsies can have the same IM detection rate as an HD-WLE examination with the Seattle protocol while requiring fewer biopsies. In addition, NBI targeted biopsies can detect more areas with dysplasia. Regular appearing NBI surface patterns did not harbour high-grade dysplasia/cancer, suggesting that biopsies could be avoided in these areas.

Prospective assessment of the utility of EUS in the evaluation of gallstone pancreatitis

BACKGROUND The ability to identify common bile duct stones by noninvasive means in patients with acute biliary pancreatitis is limited. The aim of this study was to prospectively evaluate the ability of endosonography (EUS) to identify cholelithiasis and choledocholithiasis and predict disease severity in patients with nonalcoholic pancreatitis. METHODS EUS was performed immediately before endoscopic retrograde cholangiopancreatography (ERCP) by separate blinded examiners within 72 hours of admission. Gallbladder findings were compared between EUS and transabdominal ultrasonography (US). Using endoscopic extraction of a bile duct stone as the reference standard for choledocholithiasis, the diagnostic yield of EUS was compared with transabdominal US and ERCP. Features identified during endosonographic imaging of the pancreas were correlated with length of hospitalization. RESULTS Thirty-six patients were studied. EUS and transabdominal US were concordant in their interpretation of gallbladder findings in 92% of patients. The sensitivity of transabdominal US, EUS, and ERCP for identifying choledocholithiasis was 50%, 91%, and 92% and the accuracy was 83%, 97%, and 89%, respectively. Length of hospital stay was longer in patients with peripancreatic fluid (9.2 vs. 5.7 days, p < 0.1) and shorter in patients with coarse echo texture (2.6 vs. 7.2 days, p < 0.05) demonstrated on EUS. CONCLUSIONS EUS can reliably identify cholelithiasis and is more sensitive than transabdominal US in detecting choledocholithiasis in patients with biliary pancreatitis. EUS may be used early in the management of patients with acute pancreatitis to select those who would benefit from endoscopic stone extraction. The utility of EUS for predicting pancreatitis severity requires further investigation.

Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung

BACKGROUND Endoscopic ultrasound (EUS)-guided fine needle aspiration is a safe, cost-effective procedure that can confirm the presence of mediastinal lymph node metastases and mediastinal tumor invasion. We studied the accuracy of EUS in a large population of lung cancer patients with and without enlarged mediastinal lymph nodes on computed tomographic (CT) scan. METHODS From 1996 to 2000 all patients referred to our institution with lung tumors and no proven distant metastases were considered for EUS and surgical staging. Patients had endoscopic ultrasound with fine needle aspiration of abnormal appearing mediastinal lymph nodes and evaluation for mediastinal invasion of tumor (stage III or IV disease). Patients without confirmed stage III or IV disease had surgical staging. RESULTS Two hundred seventy-seven patients met the inclusion criteria, including 121 who had EUS. Endoscopic ultrasound and fine needle aspiration detected stage III or IV disease in 85 of 121 (70%). Among patients with enlarged lymph nodes on CT, 75 of 97 (77%) had stage III or IV disease detected by EUS. Among a small cohort of patients without enlarged mediastinal lymph nodes on CT, 10 of 24 (42%) had stage III or IV disease detected by EUS. For mediastinal lymph nodes only, the sensitivity of endoscopic ultrasound and CT was 87%. The specificity of EUS (100%) was superior to that of CT (32%) (p < 0.001). CONCLUSIONS Endoscopic ultrasound with fine needle aspiration identified and histologically confirmed mediastinal disease in more than two thirds of patients with carcinoma of the lung who have abnormal mediastinal CT scans. Although mediastinal disease was more likely in patients with an abnormal mediastinal CT, EUS also detected mediastinal disease in more than one third of patients with a normal mediastinal CT and deserves further study. Endoscopic ultrasound should be considered a first line method of presurgical evaluation of patients with tumors of the lung.

An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy

BACKGROUND This study compares the health care costs and effectiveness of multiple staging options for patients with esophageal cancer. Techniques studied included computed tomographic (CT) scan, endoscopic ultrasound with fine-needle aspiration biopsy (EUS-FNA), positron emission tomography (PET), thoracoscopy/laparoscopy, and combinations of these. METHODS A decision-analysis model was constructed to compare different staging strategies. Costs were derived from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases and from other Medicare reimbursement rates. Life expectancies were obtained from the 1973-1996 SEER database and adjusted for quality of life. Cost and effectiveness measures were discounted at 0% and 3% per year. Sensitivity and specificity measures were obtained from the published literature and a parallel prospective clinical trial, and all key variables were subjected to sensitivity analyses. RESULTS Under baseline assumptions, CT + EUS-FNA was the most inexpensive strategy and offered more quality-adjusted life-years, on average, than all other strategies with the exception of PET + EUS-FNA. The latter was slightly more effective but also more expensive. The marginal cost-effectiveness ratio for PET + EUS-FNA was

Esophageal Cancer Staging: Improved Accuracy by Endoscopic Ultrasound of Celiac Lymph Nodes

60,544 per quality-adjusted life-year. These findings were robust and changed very little in all of the sensitivity analyses. CONCLUSIONS The combination of PET + EUS-FNA should be the recommended staging procedure for patients with esophageal cancer, unless resources are scarce or PET is unavailable. In these instances, CT + EUS-FNA can be considered the preferred strategy.