Srinadh Komanduri

Increased Risk for Persistent Intestinal Metaplasia in Patients With Barrett's Esophagus and Uncontrolled Reflux Exposure Before Radiofrequency Ablation

BACKGROUND & AIMS Radiofrequency ablation (RFA) is a safe alternative to esophagectomy for patients with dysplastic Barretts esophagus (BE). Although some studies have indicated that RFA is effective at eradicating dysplasia, most have found that RFA is not as effective in eradicating intestinal metaplasia. We investigated whether uncontrolled reflux is associated with persistent intestinal metaplasia after RFA. METHODS Thirty-seven patients with BE underwent RFA, high-resolution manometry, and 24-hour impedance-pH testing; they received proton pump inhibitors twice daily. Patients returned every 2 months for repeat treatment or standard surveillance. Patients were classified as complete responders (CRs) if all intestinal metaplasia was eradicated in fewer than 3 ablation sessions. We analyzed clinical parameters to identify factors associated with a CR or incomplete responder (ICR). RESULTS Among the 37 patients, 22 had a CR and 15 had an ICR. Mann-Whitney U tests revealed that length of BE, size of hiatal hernia, and frequency of reflux, but not acid reflux, differed between CRs and ICRs. CRs had fewer weakly acidic events than ICRs (29.5 vs 52; P < .05) and total reflux events (33.5 vs 60; P < .05), and a trend toward fewer weakly alkaline events (1.0 vs 5.0; P = .06). No other clinical or manometric features differed between groups. CONCLUSIONS Uncontrolled, predominantly weakly acidic reflux despite twice-daily proton pump inhibitor therapy before RFA increases the incidence of persistent intestinal metaplasia after ablation in patients with BE. Length of BE and size of hiatal hernia also were associated with persistent intestinal metaplasia after RFA.

Durability and Predictors of Successful Radiofrequency Ablation for Barrett's Esophagus

BACKGROUND & AIMS After radiofrequency ablation (RFA), patients may experience recurrence of Barretts esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication have been poorly described. METHODS We used the US RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of intestinal metaplasia (IM). We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. RESULTS Among 5521 patients, 3728 had biopsies 12 months or more after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. The average follow-up period was 2.4 years after CEIM. IM recurred in 334 (20%) and was nondysplastic or indefinite for dysplasia in 86% (287 of 334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared with patients without recurrence, patients with recurrence were more likely, based on bivariate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, the likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. CONCLUSIONS BE recurred in 20% of patients followed up for an average of 2.4 years after CEIM. Most recurrences were short segments and were nondysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.

Pancreatic adenocarcinoma, version 2.2017: Clinical practice guidelines in Oncology

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

Radiofrequency ablation for refractory gastric antral vascular ectasia (with video)

BACKGROUND Gastric antral vascular ectasia (GAVE) is a cause of upper GI bleeding and chronic anemia. Although upper endoscopy with argon plasma coagulation (APC) is an accepted therapy for GAVE, many patients continue to bleed and remain transfusion dependent after therapy. Radiofrequency ablation (RFA) may provide an alternative therapeutic option for GAVE. OBJECTIVE To determine the efficacy and safety of RFA for patients with GAVE who remain transfusion dependent after APC treatment. DESIGN Open-label prospective cohort study of patients with GAVE refractory to APC. SETTING Academic tertiary referral center. PATIENTS GAVE patients with previous failed APC therapy, chronic anemia, and transfusion dependence. INTERVENTIONS Endoscopic RFA to the gastric antrum using the HALO(90) ULTRA ablation catheter until transfusion independence is achieved or a maximum of 4 sessions are performed. MAIN OUTCOME MEASUREMENTS Transfusion requirements before and after RFA. Secondary outcomes are hemoglobin before and 6 months after RFA completion, number of RFA sessions, and complications. RESULTS Twenty-one patients underwent at least 1 RFA session with ablation of GAVE lesions. At 6 months after completion of the course of RFA therapy, 18 of 21 patients (86%) were transfusion independent. Mean hemoglobin increased from 7.8 to 10.2 in responders (n = 18). Two adverse events occurred (minor acute bleeding and superficial ulceration); both resolved without intervention. LIMITATIONS Single-center, single-operator, and nonrandomized design. CONCLUSIONS RFA is safe and effective for treating patients with refractory GAVE after attempted APC.

Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

Original ResearchFull Report: Clinical—Alimentary TractIncidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

A randomized controlled cross-over trial and cost analysis comparing endoscopic ultrasound fine needle aspiration and fine needle biopsy *

Background and study aims: Techniques to optimize endoscopic ultrasound-guided tissue acquisition (EUS-TA) in a variety of lesion types have not yet been established. The primary aim of this study was to compare the diagnostic yield (DY) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for pancreatic and non-pancreatic masses. Patients and methods: Consecutive patients referred for EUS-TA underwent randomization to EUS-FNA or EUS-FNB at four tertiary-care medical centers. A maximum of three passes were allowed for the initial method of EUS-TA and patients were crossed over to the other arm based on on-site specimen adequacy. Results: A total of 140 patients were enrolled. The overall DY was significantly higher with specimens obtained by EUS-FNB compared to EUS-FNA (90.0 % vs. 67.1 %, P = 0.002). While there was no difference in the DY between the two groups for pancreatic masses (FNB: 91.7 % vs. FNA: 78.4 %, P = 0.19), the DY of EUS-FNB was higher than the EUS-FNA for non-pancreatic lesions (88.2 % vs. 54.5 %, P = 0.006). Specimen adequacy was higher for EUS-FNB compared to EUS-FNA for all lesions (P = 0.006). There was a significant rescue effect of crossover from failed FNA to FNB in 27 out of 28 cases (96.5 %, P = 0.0003). Decision analysis showed that the strategy of EUS-FNB was cost saving compared to EUS-FNA over a wide range of cost and outcome probabilities. Conclusions: Results of this RCT and decision analysis demonstrate superior DY and specimen adequacy for solid mass lesions sampled by EUS-FNB.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipples procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett’s Esophagus

BACKGROUND & AIMS Complete eradication of Barretts esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.