Revisit the E2 Domain of Amyloid Precursor Protein: Ferroxidase, Superoxide and Peroxynitrite Scavenging Activities.

Amyloid precursor protein (APP) is the biological precursor of ß-amyloids, a known histopathological hallmark associated with Alzheimer's disease (AD). The function of APP is of great interest yet remains elusive. One of the extracellular domains of APP, the E2 domain, has been proposed to possess ferroxidase activity and affect neuronal iron homeostasis. However, contradicting evidence has been reported, and its precise role remains inconclusive. Here, we studied the Cu-binding site of the E2 domain using extended X-ray absorption fine structure (EXAFS), UV-vis, and electron paramagnetic resonance (EPR) and discovered that a new labile water ligand coordinates to the Cu(II) cofactor in addition to the four known histidines. We explored the proposed ferroxidase activity of the Cu(II)-E2 domain through reactions with ferrous iron and observed single-turnover ferrous oxidation activity with a rate up to 1.0 × 102 M-1 s-1. Cu(I)-E2 reacted with molecular oxygen at a rate of only 5.3 M-1 s-1, which would restrict any potential multiturnover ferroxidase activity to this slow rate and prevents observation of activity under multiturnover conditions. The positive electrostatic potential surface of the protein indicates possible reactivity with negatively charged small substrates such as superoxide radicals (O2•-) and peroxynitrite (ONOO-) that are major contributors to the oxidative stress prevalent in the extracellular environment. Our assays showed that Cu(I)-E2 can remove O2•- at a rate of 1.6 × 105 M-1 s-1, which is slower than the rates of native SODs. However, the reaction between Cu(I)-E2 and ONOO- achieved a rate of 1.1 × 105 M-1 s-1, comparable to native ONOO- scavenger peroxiredoxins (105-107 M-1 s-1). Therefore, the E2 domain of APP can serve as an enzymatic site that may function as a ferroxidase under substrate-limiting conditions, a supplemental O2•- scavenger, and an ONOO- remover in the vicinity of the cellular iron efflux channel and protect neuron cells from reactive oxygen species (ROS) and reactive nitrogen species (RNS) damage.

Universal Genetic Testing vs. Guideline-Directed Testing for Hereditary Cancer Syndromes Among Traditionally Underrepresented Patients in a Community Oncology Program.

Background Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognosis, treatment selection, clinical trial enrollment, and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but their applicability in an ethnically and racially diverse community hospital population is unknown. This study describes the diagnostic and incremental yield of universal multi-gene panel testing in a diverse population in a community cancer practice. Methods We completed a prospective study of proactive germline genetic sequencing among patients with solid tumor malignancies at a community-based oncology practice in downtown Jacksonville, FL, between June 2020 and September 2021. The patients were unselected for cancer type, stage, family history, race/ethnicity, and age. PGVs identified using an 84-gene next-generation sequencing (NGS) tumor genomic testing platform were stratified by penetrance. National Comprehensive Cancer Networks (NCCN) guidelines determined incremental PGV rates. Results Two hundred twenty-three patients were enrolled, with a median age of 63 years, 78.5% female. 32.7% were Black/African American, and 5.4% were Hispanic. 39.9% of patients were commercially insured, Medicare/Medicaid insured 52.5%, and 2.7% were uninsured. The most common cancers in this cohort were breast (61.9%), lung (10.3%), and colorectal (7.2%). Twenty-three patients (10.3%) carried one or more PGVs, and 50.2% carried a variant of uncertain significance (VUS). Though there was no significant difference in the rate of PGVs based on race/ethnicity, African Americans were numerically more likely to have a VUS reported than whites (P=0.059). Eighteen (8.1%) patients had incremental clinically actionable findings that practice guidelines would not have detected, which was higher in non-whites. Conclusions In this racially/ethnically and socioeconomically diverse cohort, universal multi-gene panel testing (MGPT) increased diagnostic yield over targeted guideline-informed testing. Rates of VUS and incremental PGV were higher in non-white populations.

Fine-needle aspiration of pancreatic cystic lesions: a randomized study with long-term follow-up comparing standard and flexible needles.

BACKGROUND: Pancreatic cystic lesions (PCLs) are increasingly found on cross-sectional imaging, with the majority having a low risk for malignancy. The added value of fine-needle aspiration (FNA) in risk stratification remains unclear. We evaluated the impact of three FNA needles on diagnostic accuracy, clinical management, and the ability to accrue fluid for tumor markers. METHODS: A multicenter prospective trial randomized 250 patients with PCLs ≥ 13 mm 2:1:1 to 19G Flex, 19G, and 22G needles with crossover for repeated FNA procedures. Diagnostic accuracy was established at 2-year follow-up, with the final diagnosis from surgical histopathology or consensus diagnosis by experts based sequentially on clinical presentation, imaging, and aspirate analysis in blinded review. RESULTS: Enrolled patients (36 % symptomatic) had PCLs in the head (44 %), body (28 %), and tail (26 %). Percentage of cyst volume aspirated was 78 % (72 % - 84 %) for 19G Flex, 74 % (64 % - 84 %) for 22G, and 73 % (63 % - 83 %) for 19G (P = 0.84). Successful FNA was significantly higher for 19G Flex (89 % [82 % - 94 %]) and 22G (82 % [70 % - 90 %]) compared with 19G (75 % [63 % - 85 %]) (P = 0.02). Repeated FNA was required more frequently in head/uncinate lesions than in body and tail (P < 0.01). Diagnostic accuracy of the cyst aspirate was 84 % (73 % - 91 %) against histopathology at 2-year follow-up (n = 79), and 77 % (70 % - 83 %) against consensus diagnosis among nonsurgical cases (n = 171). Related serious adverse events occurred in 1.2 % (0.2 % - 3.5 %) of patients. CONCLUSIONS: Our study results demonstrate a statistically significant difference among the three needles in the overall success rate for aspiration, but not in the percentage of cyst volume aspirated. Flexible needles may be particularly valuable in sampling cystic PCLs in the pancreatic head/uncinate process.

Changes in the Magnitude of the Individual and Combined Effects of Contaminants, Warming, and Predators on Tropical Cladocerans across 11 Generations.

A massive challenge in ecotoxicology is assessing how the interaction of contaminants, climate change, and biotic stressors shapes the structure and functions of natural populations. Furthermore, it is not known whether contemporary evolutionary responses to multiple stressors across multigenerations may alter the interaction of these stressors. To address these issues, we exposed Moina dubia to lead (Pb, 50 µg/L) under two temperatures (25 and 28 °C) with/without predator cues from climbing perch (Anabas testudineus) for 11 generations (F1-F11). We assessed changes in M. dubia fitness, including development time, adult size, lifespan, fecundity, and neonate production. We found strong negative effects of Pb, elevated temperature, and predator cues on the fitness of M. dubia. Strikingly, Pb-induced reduction in the performance of M. dubia was stronger at 25 °C and in the absence of predator cues. The individual and interactive effects of Pb, temperature, and predator cues on M. dubia were stronger across F1-F9 and generally leveled off in F10-F11. Our results highlight the high vulnerability of M. dubia to multiple stressors, thus weakening top-down control on algal blooms in eutrophic lakes. Our study underscores the importance of integrating evolutionary responses in realistic ecotoxicological risk assessments of contaminants interacting with climatic and biotic stressors.

Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.

BACKGROUND & AIMS: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). METHODS: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. RESULTS: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%). CONCLUSIONS: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.

Prospective study of the feasibility of point-of-care testing strategy for carbapenem-resistant organism detection.

BACKGROUND/AIMS: In an investigator-initiated, prospective study, we evaluated the feasibility of a five-gene sequence point-of-care (POC) testing strategy (Xpert CARBA-R Assay, Cepheid Inc., Sunnyvale, CA, USA), compared to reference laboratory PCR (48 - 72 hours turnaround time, two gene sequences), in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and in a hospital outbreak investigation. METHODS: After informed consent, patients undergoing ERCP (September 2015 - April 2016, n = 191) at Mayo Clinic and potential hospital contacts (n = 9) of an index carbapenem-resistant organism (CRO)-positive inpatient were included. Two rectal swabs, one each for reference and POC assays were obtained. The Xpert CARBA-R Assay enables qualitative rapid detection of five beta-lactamase gene sequences associated with carbapenem-non-susceptibility in Gram-negative bacteria. Feasibility parameters (specimen processing and assay run time, ease of use) and percent agreement between the tests were calculated using JMP Pro11 (SAS Corp, Cary, NC, USA). RESULTS: Mean age was 62 ±â€Š15 years; 108 (54 %) were male. Both tests were successfully performed in all patients. The POC test was rated by endoscopy nurses as easy/very easy to conduct in 193 patients (97 %); median assay run time and median time for specimen collection and processing were 55 minutes (interquartile range IQR: 53 - 55 minutes) and 3 minutes (IQR: 3 - 6 minutes), respectively. In 200/201 (99.5 %) tests, there was agreement between the POC and reference PCR. CONCLUSIONS: The more comprehensive POC CRO testing of patients in the endoscopy suite is feasible and results are available in < 1 hour. This strategy may enable rapid risk stratification of duodenoscope exposure to CRO and potentially improve operational efficiency and decrease costs.

An Unusual Suspect: Lymphoepithelial Cyst of the Pancreas.

Lymphoepithelial cysts (LECs) of the pancreas are benign, rare pancreatic cysts that are found predominantly in men. These cysts can present as a diagnostic conundrum given their rarity and difficulty of distinguishing these cysts from those with malignant potential. We present an incidental case of a LEC in a middle-aged man.

Pancreatitis before pancreatic cancer: clinical features and influence on outcome.

OBJECTIVES: Pancreatitis is considered a possible risk factor for and a presentation of pancreatic adenocarcinoma (PA). We aimed to evaluate a large PA patient registry to determine whether prior history of pancreatitis influenced survival. METHODS: We retrospectively analyzed the Mayo Clinic Biospecimen Resource for Pancreas Research database from January 1992 to September 2011. Data collected included demographic characteristics, history of tobacco or alcohol use, diabetes mellitus (DM), cholelithiasis, pseudocyst, and details regarding PA. Clinical characteristics and outcomes of PA patients with pancreatitis were compared with PA patients without pancreatitis history. RESULTS: We analyzed 2573 patients with PA diagnosis. Among these patients, 195 (8%) were identified who had pancreatitis diagnosis ≥ 10 days before PA diagnosis. The cohort with pancreatitis history included more patients with DM (30% vs. 18%; P<0.001) and more smokers (68% vs. 58%; P=0.02). Compared with patients without pancreatitis history, these patients received diagnoses of PA at a younger age (63 vs. 65 y; P=0.005) and earlier stage (stages I and II; 52% vs. 37%; P<0.001). A greater percentage had history of surgery with curative intent (50% vs. 43%; P=0.001) and significantly better survival [median (range), 387 d (314 to 460 d) vs. 325 d (306 to 344 d); P=0.003]. CONCLUSIONS: Patients with PA and pancreatitis had more weight loss and DM, but had PA diagnosis at an earlier stage, were more likely to have pancreatic surgery, and therefore better survival than PA patients without pancreatitis, likely due to the earlier diagnosis. Further studies are needed to evaluate whether screening for PA in patients with pancreatitis history would provide survival benefit.

Endoscopic treatment of anastomotic biliary strictures after living donor liver transplantation: outcomes after maximal stent therapy.

BACKGROUND: Living-donor liver transplantation (LDLT) has emerged as a viable strategy in an era of organ shortage. However, biliary strictures are a common complication of LDLT, and these strictures frequently require surgical revision after unsuccessful endoscopic therapy. The optimal endoscopic treatment for anastomotic biliary strictures (ABSs) after LDLT is undefined. OBJECTIVE: To determine the outcome of an aggressive endoscopic approach to ABSs after LDLT that uses endoscopic dilation followed by maximal stent placement. DESIGN: A retrospective study. SETTING: A tertiary-care academic medical center. PATIENTS: Forty-one patients with a diagnosis of ABS. INTERVENTIONS: Endoscopic retrograde cholangiography with balloon dilation and maximal stenting. MAIN OUTCOME MEASUREMENTS: Stricture resolution, stricture recurrence, and complication rates. RESULTS: Of 110 LDLTs completed, a biliary stricture developed after transplantation in 41 (37.3%), which included 38 patients with duct-to-duct anastomosis. The median (interquartile range [IQR]) follow-up time is 74.2 (2.5-120.8) months. Among them, 23 (60.5%) were male, and 20 (52.6%) had bile leakage associated with ABSs. The median time (IQR) to the development of an ABS after LDLT was 2.1 (1.2-4.1) months. Endoscopic retrograde cholangiography was attempted as initial therapy in all patients: 32 were managed entirely by endoscopic therapy, and 6 required initial percutaneous transhepatic cholangiography (PTC) to cross the biliary stricture, with endoscopic therapy performed thereafter. A median (IQR) of 4.0 (3.0-5.3) endoscopic interventions and 7.0 (4.0-10.3) stents were required to resolve the stricture. The time from the first intervention to stricture resolution was 5.3 (range 3.8-8.9) months. Biochemical markers including aspartate transaminase (76 vs 39 U/L, P = .001), alanine transaminase (127.5 vs 45.5 U/L, P < .001), alkaline phosphatase (590 vs 260 IU/L, P < .001), and total bilirubin (2.57 vs 1.73 mg/dL, P = .017) significantly improved after intervention. Recurrent stricture was observed after initial treatment in 8 (21%) patients. All recurrences were successfully re-treated endoscopically. All patients have been managed without surgical revision or retransplantation, resulting in 100% success by an intention-to-treat analysis. LIMITATIONS: Retrospective study, small sample size. CONCLUSIONS: In this series, aggressive endoscopy-based treatment with maximal stent placement strategy allows 100% resolution of all duct-to-duct ABSs after LDLT without the need for surgical intervention or retransplantation.

Gastric polyps: a review of clinical, endoscopic, and histopathologic features and management decisions.

The increasing use of endoscopy has led to more discernable abnormalities in the stomach, including polyps. Gastric polyps encompass a spectrum of pathologic conditions that can vary in histology, neoplastic potential, and management. Despite their high prevalence, there is a paucity of literature to support management and treatment decisions for endoscopists. The goal of this review is to summarize clinical, endoscopic, and histopathologic features of various polyps, review syndromes associated with such polyps, and provide management recommendations.

Confocal endomicroscopy (CEM) improves efficiency of Barrett surveillance.

BACKGROUND: Endoscopists with extensive experience with confocal endomicroscopy (CEM) have demonstrated that this technology is useful for Barrett's esophagus (BE) surveillance. However, data on endoscopists with minimal experience with this technique are limited. HYPOTHESIS: For BE surveillance, an endoscopist with minimal experience in CEM-guided biopsy would achieve a similar diagnostic yield with fewer biopsies when compared to the random 4-quadrant biopsy protocol. OBJECTIVE: To compare the diagnostic yields of CEM-guided biopsy technique with the random 4-quadrant biopsy protocol. DESIGN: Randomized controlled trial. SETTING: Tertiary care center. PATIENTS: Patients with BE. METHODS: Out of 18 patients who underwent routine BE surveillance, 11 and 7 were randomly assigned to group A (CEM-guided) and to group B (random 4-quadrant biopsy), respectively. The pathologists were blinded to all clinical information. RESULTS: Mean length of endoscopic Barrett was similar in both groups, (5.1 vs. 6.3 cm, p=0.51). The diagnostic yields for detecting SIM (63.6% vs. 59.5%, p=0.5), low grade dysplasia (11. 6% vs. 11.2%, p=NS), high grade dysplasia (10.1% vs. 11.5%, p=0.88). Although the total number of individual mucosal biopsy performed were 52% lower in the CEM group (129 vs. 269), the overall diagnostic yield (85.3% vs. 82.2%, p=0.53) was similar in both groups. LIMITATIONS: Small sample size. CONCLUSIONS: For BE surveillance, limited data suggested that endoscopists with minimal experience in CEM can effective use this technology for "smart" biopsy to decrease the need for intense tissue sampling but without lowering the diagnostic yield in detecting dysplasia.

¹8F-FDG PET/CT imaging of the pancreas: spectrum of diseases.

Since the introduction of integrated positron emission tomography-computed tomography (PET/CT), it has a great impact on the field of oncology. Comparing to other conventional scanners, only PET/CT is capable of providing important information on accurate detecting, staging/restaging, and post-therapeutic monitoring of many cancers. Many studies have demonstrated that PET/CT changes the management in approximately 30% of all cancer patients. Because 2-((18)F)-fluoro-2-deoxy-D-glucose (FDG) is a nonspecific tracer, understanding the PET/CT limitations and pitfalls for various pancreatic conditions can lead to more accurate interpretation of PET/CT images, which ultimately would impact patient care. As a result, it is important for radiologists and other clinicians to familiarize themselves with a wide spectrum of pancreatic PET/CT findings simulating cancer from benign entities.

Appropriate use of endoscopy in the diagnosis and treatment of gastrointestinal diseases: up-to-date indications for primary care providers.

The field of endoscopy has revolutionized the diagnosis and treatment of gastrointestinal (GI) diseases in recent years. Besides the 'traditional' endoscopic procedures (esophagogastroduodenoscopy, colonoscopy, flexible sigmoidoscopy, and endoscopic retrograde cholangiopancreatography), advances in imaging technology (endoscopic ultrasonography, wireless capsule endoscopy, and double balloon enteroscopy) have allowed GI specialists to detect and manage disorders throughout the digestive system. This article reviews various endoscopic procedures and provides up-to-date endoscopic indications based on the recommendations of American Society for Gastrointestinal Endoscopy and American Cancer Society for primary care providers in order to achieve high-quality and cost-effective care.

The Association of Ménétrier Disease with Ulcerative Colitis: A Case Report with Implications on the Pathogenesis of Ménétrier Disease.

Ménétrier disease (MD) is a rare hypertrophic condition of the gastric mucosa. The unusual association of MD with ulcerative colitis (UC) has been reported in the literature in eight cases. Transforming growth factor-alpha (TGF-alpha) is overexpressed in UC and appears to play a role in colonic healing and repair. Overproduction of TGF-alpha in murine stomach has been shown to induce gastric hypertrophy similar to MD. It can be hypothesized that increased expression of TGF-alpha may occur in the gastric mucosa in patients with UC and may lead to MD. We report the ninth case of MD associated with UC. The role of TGF-alpha and treatment with cetuximab are discussed.

Digital image analysis is a useful adjunct to endoscopic ultrasonographic diagnosis of subepithelial lesions of the gastrointestinal tract.

OBJECTIVE: The purpose of this study was to explore the role of digital image analysis in differentiating endoscopic ultrasonographic (EUS) features of potentially malignant gastrointestinal subepithelial lesions (SELs) from those of benign lesions. METHODS: Forty-six patients with histopathologically confirmed gastrointestinal stromal tumors (GISTs), carcinoids, and lipomas who had undergone EUS evaluation were identified from our database. Representative regions of interest (ROIs) were selected from the EUS images, and features were extracted by texture analysis. On the basis of these features, an artificial neural network (ANN) was built, trained, and internally validated by unsupervised learning followed by supervised learning. Outcomes were the performance characteristics of the ANN. RESULTS: A total of 106, 111, and 124 ROIs were selected from EUS images of 8, 10, and 28 patients with lipomas, carcinoids, and GISTs, respectively. For each ROI, 228 statistical parameters were extracted and later reduced to the 11 most informative features by principal component analysis. After training with 50% of the data, the remainder of the data were used to validate the ANN. The model was "good" in differentiating carcinoids and GISTs, with area under the receiver operating characteristic curve (AUC) values of 0.86 and 0.89, respectively. The model was "excellent" in identifying lipomas correctly, with an AUC of 0.92. CONCLUSIONS: Digital image analysis of EUS images is a useful noninvasive adjunct to EUS evaluation of SELs.

Risk factors for pancreatic adenocarcinoma and prospects for screening.

Pancreatic cancer has one of the worst survival rates of any cancer and is the fourth leading cause of cancer mortality. Early detection and surgery are the patient's best chance for cure. However, symptoms are typically vague and occur when the cancer is unresectable. Population-based mass screening is not practical for this rare disease, though screening and early detection in asymptomatic high-risk patient populations may be indicated.

The natural history of a branch duct intraductal papillary mucinous neoplasm in a patient with Lady Windermere syndrome: a case report.

CONTEXT: "Low-risk" branch duct intraductal papillary mucinous neoplasm (IPMN) is defined as pancreatic epithelial cellular proliferation of small branch ducts that lack malignant characteristics. At present, our understanding of the natural history of "low-risk" branch duct IPMN is still evolving. Lady Windermere syndrome is a disorder seen in non-smoking women with no pre-existing pulmonary disease affecting the lingula and/or right middle lobe with Mycobacterium avium-intracellulare complex. We present a case with pancreatic adenocarcinoma after a six-year surveillance of "low-risk" branch duct IPMN in an asymptomatic elderly white woman with Lady Windermere syndrome. CASE REPORT: A 79-year-old woman was referred to our institution because of pancreatic cystic abnormalities and elevated carbohydrate antigen 19-9 (CA 19-9). While at our institution, she was also diagnosed with Lady Windermere syndrome. Multiple abdominal imaging studies, endoscopic retrograde cholangiopancreatography, computer tomography, and magnetic resonance cholangiopancreatography (MRCP) were performed in the ensuing 6 years, all consistent with "low-risk" branch duct IPMN. No progression was seen until year 6 when MRCP showed a 2 cm pancreatic cancer. Because of multiple comorbidities, the patient chose chemotherapy over a pancreaticoduodenectomy. She developed respiratory failure and died after one cycle of gemcitabine. CONCLUSIONS: "Low-risk" branch duct IPMN may be a heterogeneous disease in which some cases can transform into malignant pancreatic neoplasms despite the absence of the so-called "high risk" features on imaging studies. Clinical management, therefore, requires individualized flexibility. In addition, when there is coexistence of Lady Windermere syndrome and pancreatic cancer, prompt diagnosis and treatment of Lady Windermere syndrome should be considered prior to chemoradiotherapy or surgery.

Multimodality imaging of esophageal perforation by a wire bristle.

Complete extra-esophageal migration of a foreign object is rare. Its early and accurate diagnosis by complementary imaging modalities is crucial for a successful extraction. We present a case of ingested wire bristle, which completely traversed the esophageal mucosa to position itself in the soft tissue of the left neck adjacent to the internal carotid artery. We discuss the importance of imaging in the detection of migrating foreign bodies, and raise awareness of this serious complication.

Circumferential and focal ablation of Barrett's esophagus containing dysplasia.

OBJECTIVES: Dysplasia in a Barrett's esophagus (BE) is associated with an increased risk for developing esophageal adenocarcinoma. Ablation using the HALO system has shown promise for the treatment of BE with dysplasia. The objective of this study was to assess the safety and efficacy of a stepwise regimen of circumferential and focal ablation using the HALO system for the treatment of BE with dysplasia. METHODS: BE patients with low-grade dysplasia (LGD) or high-grade dysplasia (HGD) were enrolled. Primary circumferential ablation was followed every 3 months by further circumferential ablation or focal ablation until complete endoscopic eradication of BE was achieved. At 3- or 6-month intervals, depending on baseline grade, targeted and four quadrant random biopsies were obtained to assess the histological response to ablation. A complete response (CR) is defined as all biopsies negative for intestinal metaplasia (IM) (CR-IM) or dysplasia (CR-D) at last available follow-up. RESULTS: A total of 63 patients were treated (57 men; median age 71 years; median BE length 5 cm), with worst grade of dysplasia being LGD (n=39) and HGD (n=24). Follow-up is available for 62 patients (median 24 months). Overall, CR-IM is 79% and CR-D is 89%. For the LGD cohort, CR-IM is 87% and CR-D is 95%. For the HGD cohort, CR-IM is 67% and CR-D is 79%. CONCLUSIONS: Stepwise circumferential and focal ablation of BE containing dysplasia appears to be a safe and effective intervention, achieving a CR for dysplasia in 95% and 79% of LGD and HGD patients, respectively.