Michael B. Kimmey

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.)

DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis

The objective of the present study was to determine whether abnormal epithelial DNA content (aneuploidy) in colonic biopsy specimens from ulcerative colitis (UC) patients correlated with and predicted histological progression to dysplasia. Aneuploidy was absent in 20 low-cancer risk patients. In 81 high-cancer risk patients aneuploidy correlated significantly with the severity of histological abnormality (negative, indefinite, dysplasia, or cancer). Statistically our data suggest that many more biopsy specimens than are usually taken are needed to detect focal dysplastic lesions. Prospective study of 25 high risk patients without dysplasia revealed 5 with aneuploidy, all of whom progressed to dysplasia in 1-2.5 years, whereas 19 patients without aneuploidy did not progress to either aneuploidy or dysplasia within 2-9 years. Our data indicate that aneuploidy in mucosal biopsy specimens correlates with histological grade and identifies a subset of patients without dysplasia who are more likely to develop it. It was concluded that more frequent and extensive colonoscopic surveillance of this minority subset of high risk patients and less frequent surveillance in the remaining majority may reduce cost and detect more curable lesions.

Ursodiol Use Is Associated with Lower Prevalence of Colonic Neoplasia in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

Patients with ulcerative colitis have an increased risk for colorectal neoplasia; this risk approaches 0.5% to 1% per year of disease. The extent and duration of colitis, as well as age at onset of disease, are important risk factors for neoplastic progression (1, 2). Primary sclerosing cholangitis is a chronic inflammatory disease of the biliary tract that occurs in 2% to 4% of patients with ulcerative colitis (3-5). Although the data are still controversial, most studies have shown that patients with ulcerative colitis and primary sclerosing cholangitis are at even higher risk for colonic neoplasia than are those with ulcerative colitis alone (6-11). The risk for colonic dysplasia or cancer in patients with ulcerative colitis and primary sclerosing cholangitis approaches 50% after 25 years of colitis (6-8). Epidemiologic studies suggest that environmental and dietary factors are important in the development of colorectal cancer (12). High-fat diets predispose to colorectal cancer, in part because they generate tumor-promoting secondary bile acids (13, 14). Conversely, the use of aspirin and other nonsteroidal anti-inflammatory drugs is associated with reduced risk for colorectal cancer and adenomatous polyps (15-17). Controversy surrounds the potential chemoprotective role of sulfasalazine in patients with ulcerative colitis (18, 19). Ursodiol, the 7--epimer of chenodeoxycholic acid, has been used in patients with primary sclerosing cholangitis because it substantially improves biochemical indices of liver function, although overall disease progression does not appear to be affected (20). Ursodiol use reduces the colonic concentration of the secondary bile acid deoxycholic acid (21). Although experimental evidence in animal models suggests that ursodiol administration inhibits colonic carcinogenesis, no clear evidence of inhibitory activity has been demonstrated in human studies (7, 22, 23). We sought to determine whether ursodiol use is associated with lower risk for colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis. Methods Patients We studied 59 patients with ulcerative colitis and primary sclerosing cholangitis who were enrolled in the colonoscopic surveillance program at the University of Washington, Seattle, Washington. These patients were involved in a research study of colonic surveillance in ulcerative colitis according to a protocol approved by the Human Subjects Division of the University of Washington. Forty-three patients were male and 16 were female. The diagnosis of primary sclerosing cholangitis was based on conventional cholangiographic criteria. Confirmatory histologic findings in the 35 patients who underwent liver biopsy included concentric periductal fibrosis, destructive inflammatory lesions of ducts, changes of ductal obstruction, or ductopenia ( 50% of at least 20 portal tracts without a duct). The diagnosis of ulcerative colitis was made according to standard histologic criteria: presence of basal lymphoplasmacytosis and distortion of crypt architecture, defined by the presence of two or more branched or irregularly shaped crypts in a single mucosal biopsy specimen. Clinical Variables Clinical variables were abstracted from the medical record and patient interview. Study groups were defined according to whether patients had ever used ursodiol. For all patients whose medical records failed to mention ursodiol use, confirmation was made by direct patient interview. All medications were carefully noted: specifically, the dates of use of ursodiol, sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, azathioprine, cyclosporine, and methotrexate. Estrogen use and menstrual status were assessed in women. Age at onset of symptomatic colitis and date of diagnosis of sclerosing cholangitis were also noted. To estimate the severity of liver disease, ChildPugh class was calculated at the time of each surveillance colonoscopy. For patients who had previously undergone orthotopic liver transplantation, a separate classification was created to reflect the fact that they had had severe liver disease despite a normal current ChildPugh score. Surveillance Colonoscopy for Diagnosis of Dysplasia Colonoscopy was performed every 3 years unless indefinite or low-grade dysplasia or aneuploidy was detected, in which case-patients underwent yearly colonoscopy. Patients who had high-grade dysplasia were referred for colectomy. At colonoscopy, biopsy samples were obtained from flat mucosa (by using a large cupped biopsy forceps) from four quadrants at 10-cm intervals from the cecum through the descending colon and at 5-cm intervals in the sigmoid colon and rectum. Any mucosal irregularity or polyp was sampled separately. The mean number of biopsy samples obtained per colonoscopy was 46.8 1.5. The biopsy samples were oriented submucosal-side-down on monofilament plastic mesh and placed in Hollande fixative. All biopsy samples were step-serial sectioned, stained with hematoxylin and eosin, and evaluated by an experienced gastrointestinal pathologist who had no knowledge of the clinical history or colonoscopic findings. The histologic criteria for the diagnosis and grading of dysplasia established by the Inflammatory Bowel Disease/Dysplasia Morphology Study Group were applied, except that the category indefinite for dysplasia was not subdivided (24). Statistical Analysis Study groups were defined according to whether the patient had ever used ursodiol. The primary outcome studied was occurrence of colonic dysplasia. A patient was defined as having achieved the outcome if he or she was known to have dysplasia at any point up to the last surveillance. Hence, the fraction of patients with the dysplasia outcome represented the prevalence of ever having had a diagnosis of dysplasia. For the primary analysis, patients whose biopsies were read as indefinite for dysplasia were combined with those whose biopsies were negative for dysplasia. Two secondary analyses were performed. In the first, all patients classified as indefinite for dysplasia were excluded from the analysis. In the second, the outcome was changed to high-grade dysplasia rather than low-grade dysplasia and high-grade dysplasia. For all analyses, ursodiol use and other variables were assessed up to the time of the outcome or last surveillance. Other variables assessed were use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, or methotrexate; duration of sclerosing cholangitis; duration of ulcerative colitis; ChildPugh class; duration of ursodiol use; age at onset of colitis; and sex. Unpaired t-tests and the Fisher exact test were used to compare means and proportions, respectively. Unadjusted odds ratios were estimated directly from 2 2 tables for ursodiol use versus outcome status, and adjusted odds ratios were estimated by using logistic regression. MathSoft S-Plus 3.4 (MathSoft, Inc., Seattle, Washington) and GraphPad Prism 2.01 (GraphPad Software, San Diego, California) statistical software packages were used. Role of the Funding Source The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the study for publication. Results Fifty-nine patients with ulcerative colitis and primary sclerosing cholangitis were enrolled in the colonoscopic surveillance program. Forty-one patients (69%) had used ursodiol, and 18 (31%) had never used ursodiol. Characteristics of ursodiol users and nonusers are shown in Table 1. Twenty-six patients (44%) had a diagnosis of dysplasia at some time during surveillance; no patient developed cancer. Table 1. Patient Characteristics Of the 26 patients who had dysplasia, 50% (13 of 26) had used ursodiol compared with 85% (28 of 33) of patients with no dysplasia. This difference in ursodiol use was highly significant, with an odds ratio of 0.18 (CI, 0.05 to 0.61; P=0.005) (Table 2). The negative association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of ulcerative colitis, duration of ulcerative colitis, duration of sclerosing cholangitis, ChildPugh class, and use of sulfasalazine (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P=0.01) (Table 3). Results were similar when treatment with 5-aminosalicylic acid, prednisone, cyclosporine, azathioprine, or methotrexate and number of surveillance colonoscopies were included in the model. Because a large number of covariates were included in the final logistic regression model relative to the sample size of 59, computer simulations were performed to check the stability of the modeling procedure. Both the Pvalue and the 95% confidence interval were reliable when the true odds ratio was assumed to be 0.14 to 1.0. Table 2. Medication Use and Development of Dysplasia Table 3. Multivariate Analysis of Risk Factors for Dysplasia Among patients who used ursodiol, the mean duration of use was 3.5 years for those who progressed to dysplasia compared with 4.2 years for those who did not progress to dysplasia (P>0.2). The mean dosage was 9.9 0.7 mg/kg per day in those who progressed to dysplasia and 8.9 0.5 mg/kg per day in those who did not progress to dysplasia (P>0.2). The relationship between total accumulated ursodiol dose (dose duration of use) and progression to dysplasia was not significant (P>0.2). Sixteen of 59 patients (27%) were indefinite for dysplasia at their most advanced colonic histologic stage. In a secondary analysis that excluded these 16 patients, ursodiol use was still negatively associated with colonic dysplasia (odds ratio, 0.21 [CI, 0.05 to 0.99]; P=0.05). After controlling for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, ChildPugh class, and use of sulfasalazine, the adjusted odds ratio was 0.20 (CI, 0.03 to 1.5; P=0.12). Eleven of the 59 patients (19%) had a diagnosis of high-grade dysplasia duri

Histologic correlates of gastrointestinal ultrasound images.

Endoscopic ultrasound imaging has potential for improving the diagnosis of gastrointestinal disease. However, the anatomic correlates of gastrointestinal ultrasound images have not been precisely defined. We have compared ultrasound images with the corresponding histologic sections of 81 specimens of resected and postmortem, normal and diseased gastrointestinal tissue. The five layers seen on ultrasound images of the normal gastrointestinal tract correspond to (1) superficial mucosa, (2) deep mucosa, (3) submucosa plus the acoustical interface between the submucosa and muscularis propria, (4) muscularis propria minus the acoustical interface between the submucosa and muscularis propria, and (5) serosa and subserosal fat. This interpretation takes into consideration the echoes produced by the tissue layers and the echoes produced by the interfaces between layers. Abnormal findings on ultrasound images of neoplastic and inflammatory diseases correspond to histologic tissue structure. When properly interpreted, ultrasound images of the gastrointestinal wall can provide potentially useful diagnostic information.

Early Diagnosis and Treatment of Pancreatic Dysplasia in Patients with a Family History of Pancreatic Cancer

Pancreatic cancer is the fourth leading cause of cancer death in the United States, and its incidence is increasing. At the time of diagnosis, 96% to 99% of patients are incurable and have a median survival of less than 1 year (1-3). Hereditary predisposition accounts for at least 10% of cases of pancreatic cancer (4). Some inherited syndromes that confer a high risk for pancreatic cancer include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, cystic fibrosis, and hereditary pancreatitis. However, patients who inherit pancreatic cancer in an autosomal dominant fashion (familial pancreatic cancer) are at the highest risk, which can approach 50% (4, 5). Management of patients with a family history of pancreatic cancer has not been prospectively studied. Theoretically, the poor prognosis of patients with pancreatic cancer could be improved if a method for detecting precancerous, or dysplastic, changes in the pancreas was available. Current methods for evaluating patients with suspected pancreatic adenocarcinoma include endoscopic retrograde cholangiopancreatography (ERCP), abdominal computed tomography, transabdominal and endoscopic ultrasonography, and serum tumor markers. These methods of diagnosis are usually used after pancreatic cancer has developed. No prospective studies to detect precancerous lesions in the pancreas have previously been performed. We sought to determine whether laboratory, radiologic, or endoscopic findings aid in the diagnosis of early precancerous conditions of the pancreas in patients with a strong family history of pancreatic cancer. Methods Patients Fourteen patients were drawn from three separate, consecutive, unrelated kindreds (families X, Y, and Z) that had two or more members in at least two generations with pancreatic cancer (Figure 1). Primary care physicians referred the probands from the kindreds to the gastroenterology clinic at the University of Washington for pancreatic evaluation because of the strong family history of pancreatic cancer. All family members were eligible for evaluation if they were between 18 and 80 years of age and were willing to have imaging studies done and be assessed by the authors. The cohort included 8 of 20 eligible members of family X, 1 of 10 eligible members of family Y, and 5 of 6 eligible members of family Z. Patients were interviewed to ascertain the presence of diarrhea, abdominal or back pain, weight loss, and diabetes (Table 1). Eleven symptomatic patients and 3 asymptomatic patients were evaluated. The institutional review board of the University of Washington approved any K- ras analysis and genetic testing. Informed consent was obtained from all patients for all tests and procedures. Figure 1. Families X, Y, and Z. Table 1. Patient History Family X is a large pedigree of 75 members spanning five generations (Figure 1) (5). Nine family members have died of adenocarcinoma of the pancreas. Two patients in generation II and all patients in generation III had pathologic confirmation of their diagnosis. No other types of cancer are present in the family. Family X was previously tested for the hereditary pancreatitis gene, hereditary nonpolyposis colon cancer genes, and the p16 gene; no evidence of mutation was found (unpublished data). Members of this family frequently develop pancreatic endocrine or exocrine insufficiency before cancer is diagnosed; this fact can be used as a clinical marker for family members who are at greatest risk for pancreatic cancer. Eight members of family X were evaluated (Table 1). Four family members (patients X.III.2, X.III.12, X.III.17, and X.IV.30) had frequent diarrhea (one to five loose stools per day), and 1 family member (patient X.III.1) had occasional diarrhea (loose stools a few times per month). One family member with frequent diarrhea (patient X.III.17) also had chronic lower abdominal pain. Four family members had diabetes (patients X.III.1, X.III.2, X.III.12, and X.III.14), and 1 family member had a history of lightheadedness associated with hypoglycemia (patient X.IV.28). One family member was asymptomatic (patient X.IV.29). Family Y includes more than 39 members, 2 of whom died of pancreatic cancer (patients Y.III.2 and Y.IV.9); other types of cancer in the family include breast cancer, oropharyngeal cancer, and bladder cancer (Figure 1). Five family members had diabetes, including 4 who did not develop pancreatic cancer (patients Y.II.2, Y.III.3, Y.III.5, and Y.V.19) and 1 who developed cancer several months after diabetes was diagnosed (patient Y.III.20). One family member (patient Y.IV.5) with recurrent epigastric pain and frequent diarrhea was evaluated. Family Z consists of 29 members (Figure 1). Three members died of pancreatic cancer (patients Z.II.5, Z.III.7, and Z.IV.5), which was present in both sides of the family; however, the maternal lineage seemed to develop cancer at an earlier age than the paternal lineage (45 years compared with 63 years). Prostate, stomach, and breast cancer were present in paternal family members, and diabetes and suspected liver cancer were present in maternal family members (the diagnosis of liver cancer is uncertain because objective medical information was not available). Five family members were available for evaluation (Table 1). One patient (patient Z.IV.1) had frequent loose stools, and two patients (patient Z.IV.2 and Z.V.3) had occasional loose stools (Table 1). Patients Z.IV.1 and Z.V.3 also had intermittent abdominal pain. Two family members were asymptomatic (patients Z.III.6 and Z.IV.4). Patient Z.III.6 was the link between two generations with pancreatic cancer: her mother (patient Z.II.5) and her son (patient Z.IV.5). Interventions Diagnostic Tests Laboratory tests consisted of carcinoma embryonic antigen analysis, CA19-9 analysis, and, when possible, a 3-hour glucose tolerance test (unless the patient was already known to have diabetes). Analysis for the K -ras mutation was performed in patients who underwent ERCP if sufficient pancreatic juice could be obtained. Exon 1 of the K -ras oncogene was amplified by polymerase chain reaction, and products were directly sequenced as previously described (5, 6). Imaging studies included spiral computed tomography, endoscopic ultrasonography, and ERCP. Endoscopic ultrasonography was done after conscious sedation with a mechanical radial scanning ultrasonography endoscope (Olympus UM-20, Olympus Optical Co., Tokyo, Japan). Images were recorded as prints and were videotaped. Videotapes were reviewed after examinations were done to confirm the findings. Findings on endoscopic ultrasonography and ERCP were examined by the same observer to avoid interobserver variation. Computed tomography with dual-phase and helical technique was performed by using intravenous contrast, negative oral contrast, and intravenous glucagon to maximize distention of the duodenum. Thin collimation of 3 mm was used for initial noncontrast images and for the arterial and delay phases. Needle biopsies guided by computed tomography were not done for histologic evaluation because of the risk for pancreatitis and the high risk for sampling error (most patients had no focal lesions to target). Surgery Seven patients were referred for surgery because they had abnormal findings on endoscopic ultrasonography and ERCP. They received pneumococcal, influenza, and meningococcal vaccines approximately 3 weeks before surgery in anticipation of splenectomy and subsequently had abdominal exploration and en bloc total pancreaticoduodenectomy and splenectomy to remove all pancreatic tissue. Total pancreatectomy rather than partial pancreatectomy was performed because of concerns that cancer could develop in any pancreatic remnant left in situ. Reconstruction was done by using duodenojejunostomy followed by end-side choledochojejunostomy using an antecolic jejunal limb. A feeding jejunostomy tube was placed to allow early postoperative enteral nutrition. Postoperative therapy included H2-blockers or proton-pump inhibitors as prophylaxis against marginal ulcers. One patient required segmental jejunal resection for an intramural mass found to contain a pancreatic rest on histologic examination. Results Fourteen patients were evaluated for evidence of pancreatic abnormalities, and 7 were referred for pancreatectomy on the basis of ERCP findings and family history. All 7 patients were found to have widespread dysplasia throughout the pancreas; 6 of these patients were from family X, and 1 was from family Z (Table 2). Table 2. Endoscopic, Radiologic, and Histologic Findings Diagnostic Tests Initial history showed that 6 of the 14 patients had frequent symptoms of pancreatic endocrine or exocrine insufficiency, 3 patients had occasional diarrhea, 1 patient had weight loss, 1 patient had lightheadedness associated with hypoglycemia, and 3 patients were asymptomatic. Of the patients found to have dysplasia, 6 had symptoms and 1 was asymptomatic. Of the 7 patients who did not undergo surgery, 5 had symptoms and 2 were asymptomatic (Table 1). Physical examinations were noncontributory. Laboratory analysis showed diabetes or glucose intolerance in half of the patients (7 of 14); however, most of these patients (6 of 7) were from family X, in which diabetes is a phenotypic component of the hereditary syndrome. Carcinoembryonic antigen and CA19-9 levels were tested in 8 of the 14 patients and found to be normal in all patients except patient X.III.17, who had an elevated carcinoembryonic antigen level of 10.6 g/L (normal range<5.0 g/L) but a normal CA19-9 level of 34 U/mL (normal range<35 U/mL). Analysis for the K- ras mutation was performed on pancreatic juice obtained on ERCP in 4 of the 7 patients who were subsequently found to have dysplasia. Three patients (patients X.III.1, X.III.2, and X.III.17) were positive for the K- ras mutation, and 1 patient (patient X.III.14) had no detectable mutation. Endoscopic ultrasonography was perfo

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.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS The AIM-II Trial included patients with nondysplastic Barretts esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barretts esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up

BACKGROUND For patients with Barretts esophagus (BE), life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma. Various endoscopic therapies have been used to eradicate BE. Recently circumferential radiofrequency ablation has been used with encouraging short-term results. OBJECTIVE To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE. DESIGN Prospective, multicenter clinical trial (NCT00489268). SETTING Eight U.S. centers, between May 2004 and February 2007. PATIENTS Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia (IM). INTERVENTIONS Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM. Follow-up biopsy specimens were obtained at 1, 3, 6, 12, and 30 months. Specimens were reviewed by a central pathology board. Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy (absolute indication) or endoscopic appearance suggestive of columnar-lined esophagus (relative indication). Subjects received esomeprazole for control of esophageal reflux. MAIN OUTCOME MEASUREMENTS Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months, defined as complete remission-IM (CR-IM). RESULTS At 12 months, CR-IM was achieved in 48 of 69 available patients (70% per protocol [PP], 69% intention to treat [ITT]). At 30 months after additional focal ablative therapy, CR-IM was achieved in 60 of 61 available patients (98% PP, 97% ITT). There were no strictures or buried glandular mucosa detected by the standardized biopsy protocol at 12 or 30 months, and there were no serious adverse events. LIMITATIONS This was an uncontrolled clinical trial with 2.5-year follow-up. CONCLUSION Stepwise circumferential and focal ablation resulted in complete eradication of IM in 98% of patients at 2.5-year follow-up.

Rapid-scanning forward-imaging miniature endoscope for real-time optical coherence tomography.

We developed a miniature endoscope that is capable of rapid lateral scanning and is suitable for real-time forward-imaging optical coherence tomography (OCT). The endoscope has an outer diameter of 2.4 mm, consisting of a miniature tubular lead zirconate titanate (PZT) actuator, a single-mode fiber-optic cantilever, and a graded-index lens. Rapid lateral scanning at 2.8 kHz is achieved when the fiber-optic cantilever is resonated with the PZT actuator. This allows OCT imaging to be performed by fast lateral beam scanning followed by slow depth scanning, which is different from the conventional OCT imaging sequence. Real-time OCT imaging with the endoscope operated in the new image acquisition sequence at 6 frames/s is demonstrated.

Endoscopic management of biliary strictures in liver transplant recipients: Effect on patient and graft survival

BACKGROUND Biliary strictures in liver transplant recipients cause significant morbidity and can lead to reduced patient and graft survival. METHODS Of 251 liver transplant recipients, 22 patients with biliary strictures were categorized into two groups: donor hepatic duct (n = 12) or anastomotic (n = 10). Strictures were dilated and stented. Endoscopic therapy was considered successful if a patient did not require repeat stenting or dilation for 1 year. RESULTS Patient and graft survival did not differ significantly in the 22 patients compared with patients without strictures (relative risk of death and graft survival 1.8 and 1.3). Donor hepatic duct strictures required significantly longer therapy than anastomotic strictures (median days 185 versus 67, p = 0.02). Twenty-two months after the first endoscopic treatment, 73% of the donor hepatic duct stricture group were stent free compared with 90% of the anastomotic group (p = 0.02). The former group had significantly more (p < 0.05) hepatic artery thrombosis (58.3% versus 10%), cholangitis (58.3% versus 30%), choledocholithiasis (91% versus 10%), and endoscopic interventions. No patient undergoing endoscopic treatment required retransplantation or biliary reconstruction during a median follow-up of 35.7 months. CONCLUSION Endoscopic therapy of biliary strictures after liver transplantation is effective and is not accompanied by reduced patient or graft survival.