Ram Chuttani

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.

Effect of Institution-Wide Policy of Colonoscopy Withdrawal Time ≥7 Minutes on Polyp Detection

BACKGROUND & AIMS Practice guidelines recommend that endoscopists spend at least 7 minutes examining the colonic mucosa during colonoscopy withdrawal to optimize polyp yield. The aim of this study was to determine if the implementation of an institution-wide policy of colonoscopy withdrawal time > or = 7 minutes was associated with an increase in colon polyp detection. METHODS All 42 endoscopists at our institute were asked to attain a colonoscopy withdrawal time of at least 7 minutes. Compliance with 7-minute withdrawal time was recorded for all nontherapeutic colonoscopies. Polyp detection ratio (number of polyps detected divided by number of colonoscopies performed) was computed. Regression models were used to assess the association between compliance with 7-minute withdrawal time and polyp detection. RESULTS During the study period, 23,910 colonoscopies were performed. The average age of patients was 56.8 years, and 54% were female. Colon cancer screening or surveillance was the indication for 42.5% of colonoscopies. At the beginning of the study, the polyp detection ratio was 0.48. Compliance with 7-minute withdrawal time for nontherapeutic procedures increased from 65% at the beginning of the initiative to almost 100%. However, no increase in polyp detection ratio was noted over the same period for all polyps (slope, 0.0006; P = .45) or for polyps 1-5 mm (slope, 0.001; P = .26), 6-9 mm (slope, 0.002; P = .43), or > or = 10 mm (slope, 0.006; P = .13). No association was detected when only colonoscopies performed for screening or surveillance were analyzed. CONCLUSIONS An institution-wide policy of colonoscopy withdrawal time > or = 7 minutes had no effect on colon polyp detection.

Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience.

BACKGROUND Because of the low sensitivity of current ERCP-guided tissue sampling methods, management of patients with indeterminate pancreaticobiliary strictures is a challenge. Probe-based confocal laser endomicroscopy (pCLE) enables real-time microscopic visualization of strictures during an ongoing ERCP. OBJECTIVE To document the utility, performance, and accuracy of real-time pCLE diagnosis compared with histopathology. DESIGN Prospective observational study within the framework of a multicenter registry. SETTING Five academic centers. PATIENTS This study involved 102 patients with indeterminate pancreaticobiliary strictures. INTERVENTION Clinical information, ERCP findings, tissue sampling results, and pCLE videos were collected prospectively. Investigators were asked to provide a presumptive diagnosis based on pCLE during the procedure before pathology results were available. All patients received at least 30 days of follow-up until definitive diagnosis of malignancy was established or 1-year follow-up if index tissue sampling was benign. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy, sensitivity, specificity of ERCP-guided pCLE compared with ERCP with tissue acquisition. RESULTS There were no pCLE-related adverse events in the study. We were able to evaluate 89 patients, of whom 40 were proven to have cancer. The sensitivity, specificity, positive-predictive value, and negative-predictive value of pCLE for detecting cancerous strictures were 98%, 67%, 71%, and 97%, respectively, compared with 45%, 100%, 100%, and 69% for index pathology. This resulted in an overall accuracy of 81% for pCLE compared with 75% for index pathology. Accuracy for combination of ERCP and pCLE was significantly higher compared with ERCP with tissue acquisition (90% vs 73%; P = .001). LIMITATIONS Investigators had access to all relevant clinical information, which may have biased the predictive characteristics of pCLE. CONCLUSION Probe-based CLE provides reliable microscopic examination and has excellent sensitivity and negative predictive value. The significantly higher accuracy of ERCP and pCLE compared with ERCP with tissue acquisition may support supplementing ERCP with pCLE.

Large balloon dilation vs. mechanical lithotripsy for the management of large bile duct stones: a prospective randomized study.

OBJECTIVES:The removal of large bile duct stones (>12 mm) after endoscopic sphincterotomy (EST) remains a challenging issue in therapeutic endoscopy. The aim of this prospective, randomized, controlled trial was to compare the effectiveness and complications of EST followed by large balloon dilation (LBD) with that of EST followed by mechanical lithotripsy (ML) for the management of large bile duct stones.METHODS:A total of 90 patients with large bile duct stones (12–20 mm) were randomized to EST followed by LBD (n=45) or EST followed by ML (n=45). Success rate was determined with a final cholangiogram, whereas type and rate of post-procedure complications were assessed prospectively.RESULTS:Complete bile duct stone removal was accomplished in 97.7% of patients subjected to EST–LBD as compared with 91.1% of those subjected to EST–ML (P=0.36). Post-procedure complications were observed in two (4.4%) patients subjected to EST–LBD and in nine (20%) patients subjected to EST–ML (P=0.049). Rates of pancreatitis were similar between the two groups (one case in each), as was post-endoscopic retrograde cholangio pancreatography (ERCP) hemorrhage (one case in each group). None of the patients subjected to EST–LBD developed cholangitis, while this was seen in six patients subjected to EST–ML (0.0 vs. 13.3%, P=0.026). One patient subjected to EST–ML developed perforation, which was successfully managed conservatively. None of our patients with complications died.CONCLUSIONS:EST followed by LBD is equally effective as EST followed by ML for the removal of large bile duct stones, although it is associated with fewer complications.

Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barretts esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as high-grade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.

Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid

BACKGROUND Pancreatic-cyst fluid carcinoembryonic antigen (CEA) levels and molecular analysis are useful diagnostic tests in differentiating mucinous from nonmucinous cysts. OBJECTIVE To assess agreement between CEA and molecular analysis for differentiating mucinous from nonmucinous cysts. DESIGN Retrospective analysis. SETTING Academic medical center. METHODS Patients who underwent EUS-guided FNA for evaluation of pancreatic cysts were identified. The following information was used to designate a cyst mucinous: the CEA criterion was CEA level >or=192 ng/mL and the molecular analysis criteria were DNA quantity >or=40 ng/microL and/or k-ras 2-point mutation and/or >or=2 allelic imbalance mutations. Pathologic analysis of cysts served as the criterion standard. RESULTS From 2006 to 2007, 100 patients met the study criteria. The average age of the patients was 63 years, 65% were women, and 30% were symptomatic. The mean diameter of pancreatic cysts was 2.5 cm. The median CEA value was 83 ng/mL (range 1-50,000 ng/mL), the mean DNA content was 16 ng/microL (range 1-212 ng/microL), 11% had K-ras mutations, and 43% had >or=2 allelic imbalance mutations. When using prespecified criteria, there was poor agreement between CEA and molecular analysis for the classification of mucinous cysts (kappa = 0.2). Poor agreement existed between CEA and DNA quantity (Spearman correlation = 0.2; P = .1), K-ras mutation (kappa = 0.3), and >or=2 allelic imbalance mutations (kappa = 0.1). Of the 19 patients for whom a final pathologic diagnosis was available, CEA had a sensitivity of 82% compared with 77% for molecular analysis. When CEA and molecular analysis were combined, 100% sensitivity was achieved. LIMITATIONS Retrospective analysis and small sample size. CONCLUSION There was poor agreement between CEA levels and molecular analysis for diagnosis of mucinous cysts. Diagnostic sensitivity was improved when results of CEA levels and molecular analysis were combined.

Analysis of Cystic Fibrosis Gener Product (CFTR) Function in Patients with Pancreas Divisum and Recurrent Acute Pancreatitis

BACKGROUND:The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP).METHODS:A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed.FINDINGS:Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (−1 mV, p < 0.0001) and pancreatic insufficient (−3 mV, p < 0.0001) patients.INTERPRETATIONS:These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis.

Intraductal US is a useful adjunct to ERCP for distinguishing malignant from benign biliary strictures

BACKGROUND Distinguishing malignant from benign biliary strictures remains a challenge. This prospective study assessed intraductal US as an adjunct to endoscopic retrograde cholangiography and tissue sampling for diagnosis of malignant and benign biliary strictures. METHODS Sixty-two patients were enrolled who had biliary strictures suspected to be malignant but with negative tissue sampling by endoscopic retrograde cholangiography, or suspected biliary strictures based on clinical manifestations and/or cross-sectional imaging. Intraductal US was performed with an over-the-wire 2.4-mm diameter 20 MHz catheter US probe. The diagnostic accuracy of endoscopic retrograde cholangiography plus tissue sampling with and without intraductal US was compared with surgical findings or clinical outcome at a 12-month follow-up (benign/malignant) in nonsurgical cases. Tissue sampling results were reported as malignant, suspicious for malignancy, atypical, or normal. Analysis was by intention-to-treat. RESULTS Two patients (3%) were excluded from analysis because the stricture could not be traversed with the intraductal US probe. Of the 60 remaining patients (37 men, mean age 64 years, range 27-89 years), 31 had malignant strictures (12 cholangiocarcinoma, 8 pancreatic, 5 metastatic, 3 gallbladder, 3 papilla), and 29 had benign strictures. Sphincterotomy was not required in any case to facilitate intraductal US. Fourteen patients (23%) underwent subsequent surgery including 11 with a preoperative diagnosis of resectable tumor. Endoscopic retrograde cholangiography/tissue sampling (atypia considered equivalent to benign) correctly identified 15 of 31 malignant strictures (p = 0.001) and all 29 benign strictures (p = 0.16) (accuracy 73%, sensitivity 48%, specificity 100%). The addition of intraductal US correctly identified 28 of 31 malignant strictures and 27 of 29 benign strictures (accuracy 92%, sensitivity 90%, specificity 93%). Of 11 patients with tumors who came to surgery, intraductal US correctly staged 4 (36%), understaged 5 (45%), missing metastatic lymph nodes in all cases and vascular invasion in 1 patient, and overstaged 2 (18%), with a false-positive diagnosis of metastatic lymph nodes in 1 and tumor mass in 1 patient who had no cancer at surgery. CONCLUSION Technically easy, intraductal US is a valuable adjunct to endoscopic retrograde cholangiography/tissue sampling that increases the ability to distinguish malignant from benign strictures. Intraductal US is unsuitable for assessing lymph nodes associated with malignant strictures.

Improved oral intake after palliative duodenal stenting for malignant obstruction: a prospective multicenter clinical trial.

OBJECTIVES:We sought to test the hypothesis that placement of a new nitinol duodenal self-expandable metallic stent (SEMS) for palliation of malignant gastroduodenal obstruction is effective and safe in allowing patients to tolerate an oral diet.METHODS:In a prospective multicenter study, SEMSs (Duodenal WallFlex, Boston Scientific) were placed to alleviate gastroduodenal obstruction in inoperable patients without the ability to tolerate solid food. The primary study end point was improvement in oral intake monitored according to the 4-point Gastric Outlet Obstruction Scoring System (GOOSS) up to 24 weeks after stent placement.RESULTS:Forty-three patients received SEMSs, which were successfully deployed on the first attempt in 41 cases (95%) and the second attempt in two (5%). Within 1 day and 7 days after SEMS placement, 52% and 75% of patients, respectively, benefited from a GOOSS increase ≥1. Resumption of solid food intake (GOOSS 2–3) was attained by 56% of patients within 7 days and 80% by 28 days. Of the patients attaining GOOSS 2–3, 48% remained on solid food until death or last follow-up. Device-related adverse events included stent occlusion/malfunction in 9% of patients and perforation in 5% of patients.CONCLUSIONS:Duodenal WallFlex stent placement promptly improves oral intake in a majority of inoperable patients with malignant gastroduodenal obstruction. In approximately half the patients achieving GOOSS 2–3, the capacity for solid food intake endures until death or last follow-up.