Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer. METHODS: Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression. RESULTS: Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE. CONCLUSIONS: RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.

Cryotherapy and Radiofrequency Ablation for Eradication of Barrett's Esophagus with Dysplasia or Intramucosal Cancer.

BACKGROUND AND AIMS: Endoscopic ablation therapy has become the mainstay of treatment of Barrett's associated dysplasia and intramucosal cancer (IMC). The widely available techniques for ablation are radiofrequency ablation (RFA) and cryotherapy. Our aim was to compare eradication rates of metaplasia and dysplasia with both these modalities. PATIENTS AND METHODS: Retrospective review of prospectively collected database of patients who underwent endoscopic therapy for Barrett's dysplasia or IMC from 2006 to 2011 was performed. Demographic features, comorbidities, and endoscopic data including length of Barrett's segment, hiatal hernia size, interventions during the endoscopy and histological results were reviewed. RESULTS: Among 154 patients included, 73 patients were in the RFA and 81 patients were in the cryotherapy group. There was complete eradication of intestinal metaplasia (CE-IM) in 81 (52.6%), complete eradication of dysplasia (CE-D) in 133 (86.4%), and persistent dysplasia or cancer in 19 patients (12.3%). Compared to RFA, cryotherapy patients were found to be older and less likely to have undergone endoscopic mucosal resection. On multivariate analysis, patients who underwent RFA had a threefold higher odds of having CE-IM than those who underwent cryotherapy (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.4-6.0, p = 0.004), but CE-D were similar between the two groups (OR 1.7, 95% CI 0.66-4.3, p = 0.28). CONCLUSIONS: Endoscopic therapy is highly effective in eradication of Barrett's associated neoplasia. Patients who underwent cryotherapy were equally likely to achieve CE-D but not CE-IM than patients who underwent RFA. Patient characteristics and preferences may effect choice of treatment selection and outcomes.

Correlation between endoscopic forceps biopsies and endoscopic mucosal resection with endoscopic ultrasound in patients with Barrett's esophagus with high-grade dysplasia and early cancer.

BACKGROUND: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or intramucosal cancer (IMC) on endoscopic forceps biopsies are referred to endoscopic therapy even though forceps biopsies do not reflect the disease extent accurately. Endoscopic mucosal resection (EMR) and endoscopic ultrasound (EUS) are frequently used for staging prior to endoscopic therapy. Our aims were to evaluate: (1) if endoscopic forceps biopsies correlated with EMR histology in these patients; (2) the utility of EUS compared to EMR; and (3) if accuracy of EUS varied based on grade of differentiation of tumor. METHODS: This is a retrospective review of patients referred to endoscopic therapy of BE with HGD or early esophageal adenocarcinoma (EAC) who underwent EMR from 2006 to 2011. Age, race, sex, length of Barrett's segment, hiatal hernia size, number of endoscopies and biopsy results and EUS findings were abstracted. RESULTS: A total of 151 patients underwent EMR. In 50 % (75/151) of patients, EMR histology was consistent with endoscopic forceps biopsy findings. EMR resulted in change in diagnosis with upstaging in 21 % (32/151) and downstaging in 29 % (44/151). In patients with HGD on EMR, EUS staging was T0 in 74.1 % (23/31) but upstaged in 25.8 % (8/31). In patients with IMC on EMR, EUS findings were T1a in 23.6 % (9/38), upstaged in 18.4 % (7/38) and downstaged in 57.8 % (22/38). EUS accurately identified EMR histology in all submucosal cancers. Grade of differentiation was reported in 24 cancers on EMR histology. There was no correlation between grade and EUS staging. CONCLUSIONS: EUS is of limited utility in accurate staging of BE patients with HGD or early EAC. Endoscopic forceps biopsy correlated with EMR findings in only 50 % of patients. Irrespective of the endoscopic forceps biopsy results, all BE patients with visible lesions should be referred to EMR.

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 Barrett's 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.

Adequacy of esophageal squamous mucosa specimens obtained during endoscopy: are standard biopsies sufficient for postablation surveillance in Barrett's esophagus?

BACKGROUND: After endoscopic eradication therapy (EET) for Barrett's esophagus (BE), surveillance of residual/recurrent intestinal metaplasia/dysplasia including subsquamous tissue is performed by using biopsy forceps. OBJECTIVE: The goal of this study was to compare the adequacy of biopsy specimens obtained from neo-squamous (post-EET patients) and native (non-BE patients) squamous mucosa. DESIGN: A case-control study using squamous biopsy specimens obtained at 2 tertiary referral centers was conducted. INTERVENTIONS: Two experienced GI pathologists reviewed specimens from patients with neo- (post-EET patients) and native (non-BE patients) squamous mucosa in a blinded fashion after developing standardized criteria to assess tissue depth. MAIN OUTCOME MEASUREMENTS: The primary outcome was the proportion of biopsy specimens that contained any amount of lamina propria. RESULTS: A total of 193 biopsy specimens (1692 tissue pieces) from 104 patients were reviewed: 163 neo- and 30 native squamous. Of all biopsy specimens, only 37% contained any amount of lamina propria, and, furthermore, fewer than 4% of specimens had sufficient lamina propria (ie, more than two thirds of the entire squamous tissue present). When examining individual squamous tissue pieces, fewer than 11% contained lamina propria. No statistically significant differences in the presence of lamina propria were detected between neo- and native squamous mucosa. CONCLUSION: The majority of esophageal squamous biopsy specimens obtained during endoscopy do not demonstrate lamina propria and subepithelial structures. This is true for both neo- and native squamous mucosa. Biopsy specimens of neo-squamous mucosa obtained after EET appear to be inadequate to exclude subsquamous intestinal metaplasia/dysplasia because lamina propria is not present in more than 60% of specimens. This has larger implications in the clinical management of BE patients after EET.

Diagnosis and management of gallbladder calculus disease.

BACKGROUND: The number and rate of cholecystectomy are increasing worldwide, although indications for operative treatment remain empirical, and several issues in the understanding of the condition are not concisely outlined. Our intention is to summarize and interpret current opinion regarding the indications and timing of cholecystectomy in calculous gallbladder disease. METHODS: Publications concerned with gallstone disease and related topics were searched for in MEDLINE using PubMed and summarized according to clinical scenarios with an emphasis on recent research. RESULTS: Only one randomized controlled trial has investigated the management (conservative vs. surgery) of patients with acute cholecystitis and several have compared early with deferred surgery. Two RCTs have examined treatment of uncomplicated, symptomatic gallstone disease. Apart from these, the overwhelming majority of publications are retrospective case series. CONCLUSIONS: Recent literature confirms that cholecystectomy for an asymptomatic or incidental gallstone is not justified. Symptomatic, uncomplicated gallstone disease may be classified into four severity groups based on severity and frequency of pain attacks, which may guide indication for cholecystectomy. Most patients below the age of 70 seem to prefer operative treatment. Acute cholecystitis may be treated with early operation if reduction of hospital days is an issue. Patients older than 70 years with significant comorbidities may forego surgical treatment without undue hazard. Symptoms following cholecystectomy remain in 25% or more and recent evidence suggest these are caused by a functional gastrointestinal disorder.

Cryotherapy for Barrett's esophagus and esophageal cancer.

PURPOSE OF REVIEW: To summarize the recent literature on endoscopic spray cryotherapy for the treatment of Barrett's esophagus and esophageal cancer. RECENT FINDINGS: Endoscopic spray cryotherapy is a relatively new ablative modality for the treatment of gastrointestinal diseases. Spray cryotherapy rapidly cools tissues by spraying them with either liquid nitrogen or rapidly expanding carbon dioxide gas. Initial, nonrandomized and uncontrolled studies show success rates comparable to other ablative modalities for the treatment of Barrett's esophagus with high-grade dysplasia, with complete eradication of dysplasia seen in 87-96% and complete eradication of intestinal metaplasia in 57-96% of treated patients. In early-stage esophageal cancer, spray cryotherapy appears to have a unique role, eliminating mucosal cancer in 75% of patients, including those who have failed other modalities. Patient tolerance of the procedure is very good. Limitations of current studies include small sample sizes and short durations of follow-up, and further studies are needed to validate the promising early results. SUMMARY: Endoscopic spray cryotherapy is a promising ablative modality for treatment of Barrett's esophagus and esophageal cancer.

Effect of the time of day on the success and adverse events of ERCP.

BACKGROUND: Physician fatigue and decreased concentration have been proposed as causes of lower completion and adenoma detection rates in afternoon colonoscopies compared with morning colonoscopies. ERCP is a technically demanding and highly operator-dependent procedure, and its success may similarly be affected in the afternoon compared with the morning. OBJECTIVE: To compare cannulation success and adverse events between ERCP procedures performed in the morning and afternoon. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Patients with no previous papillary intervention who underwent ERCP at our institution between November 2006 and November 2008. MAIN OUTCOME MEASUREMENTS: Cannulation success, procedure completion rates, length of procedures, and adverse events. RESULTS: A total of 296 patients were studied; 114 patients (38.5%) underwent a procedure in the morning and 182 patients (61.5%) underwent a procedure in the afternoon. There were 139 male patients (47.0%). The mean patient age was 59.1 years. The deep cannulation success rate was 95.3% overall, with similar rates when performed in the morning (98.3%) and afternoon (94.0%) (P = .08). When the start time was evaluated as a continuous hour-by-hour variable, there was also no significant difference in deep cannulation success rates (P = .30). Procedure completion rates were similar in both groups (morning, 93.9%; 94.0%, afternoon; P = .97). Adverse events (8.8% for morning procedures vs 7.1% for afternoon procedures, P = .61) and length of procedures (40 minutes for morning procedures vs 40 minutes for afternoon procedures, P = .87) were also similar between the 2 groups. LIMITATIONS: Small sample size and retrospective study. CONCLUSIONS: The timing of ERCP, morning versus afternoon, does not seem to affect cannulation success, procedure completion rates, length of procedures, or adverse events.

Hypoxemia during moderate sedation for gastrointestinal endoscopy: causes and associations.

BACKGROUND/AIMS: Although prolonged hypoxemia (henceforth referred to as hypoxemia) is not uncommon during moderate sedation for endoscopy, there are only sparse data regarding its relationship with medications, endoscopic intubations and ventilation patterns. We aimed to study these relationships. METHODS: 123 patients enrolled in the control arm of a randomized trial of ventilation monitoring during endoscopy were analyzed. Hypoxemia was defined as oxygen saturation of <90% for ≥15 s, and apnea as lack of respiratory activity for ≥15 s. RESULTS: There were 132 hypoxemic events; 46 (35%) and 112 (85%) events occurred within 1 and 5 min of medication administration/endoscopic intubations, and conversely, 46/638 (7%) and 112/638 (18%) of all medication administration/endoscopic intubations led to hypoxemia in 1 and 5 min, respectively. Apnea, abnormal ventilation and normal ventilation were associated with 36, 30 and 34% of all hypoxemia events, respectively. However, only 101/268 (38%) apnea/abnormal ventilation events led to hypoxemia. Significant predictors of apnea were total dose of meperidine/fentanyl 1.3 (1.02-1.6) and total dose of midazolam 0.84 (0.71-0.99). CONCLUSIONS: Hypoxemia occurs typically within 5 min of medication administration or endoscope intubation and only one third of all apnea/abnormal ventilation events eventually lead to hypoxemia.

Does anesthesiologist-directed sedation for ERCP improve deep cannulation and complication rates?

OBJECTIVES: While some gastroenterologists provide their own sedation for endoscopic retrograde cholangiopancreatography (ERCP), others utilize anesthesiologists. There is limited information comparing cannulation success and complication rates between these two approaches. Theoretically, anesthesiologist-directed sedation (ADS) may lead to an improved deep cannulation rate by virtue of using deeper and more constant levels of sedation and by removing the minute-by-minute medication management and physiologic monitoring responsibilities from the endoscopy team. AIMS: To compare ERCP deep cannulation success and complications between gastroenterologist-directed sedation (GDS) and ADS. METHODS: All ERCPs completed by senior advanced endoscopists at a tertiary referral center over a 2-year period were reviewed. During the first year, all ERCP sedation was performed with GDS utilizing a narcotic and a benzodiazepine. Due to a change in division policy and practice, during the second year, all ERCP sedation was provided by ADS. Patients with prior papillary interventions were excluded. Demographics, procedure indications, deep cannulation success, sedation provider, and procedural complications were recorded. RESULTS: A total of 367 patients were studied: 178 (48.5%) GDS and 189 (51.5%) ADS. There was no difference in the groups with respect to race, age, and gender. Four patients (2.3%) in the GDS group could not be sedated. There were two deaths, one in each group; one death was due to cholangitis/sepsis and the other was due to post-ERCP pancreatitis. The overall cannulation success rates were similar between the two groups (94.4% vs. 95.2%, P = 0.36). CONCLUSIONS: Deep ductal cannulation rates between GDS and ADS are similar.

Capnographic monitoring of respiratory activity improves safety of sedation for endoscopic cholangiopancreatography and ultrasonography.

BACKGROUND & AIMS: The Joint Commission on the Accreditation of Healthcare Organizations recommends ventilation monitoring during procedural sedation for gastrointestinal endoscopy. We sought to determine whether intervention, based on a microstream capnography-based ventilation monitoring system that has been shown to function as an early warning system for hypoxemia, would decrease hypoxemia during endoscopy. METHODS: Subjects undergoing elective endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) under procedural sedation with a combination of opioid and benzodiazepine were randomly assigned to either a study arm in which the endoscopy team was blinded to capnography or an open arm in which the endoscopy team was prompted of capnographic changes. The primary end point was the occurrence of hypoxemia; secondary end points were the occurrences of severe hypoxemia, apnea, and oxygen supplementation. RESULTS: A total of 263 subjects were enrolled; 247 were analyzed for efficacy. The numbers of hypoxemic events in the blinded and open arms were 132 and 69, respectively (P < .001). Thirty-five percent of all hypoxemic events occurred with completely normal ventilation. Hypoxemia developed in 69% of patients in the blinded arm compared with 46% in the open arm (P < .001). Severe hypoxemia percentages in the blinded and open arms were 31% and 15% (P = .004), for apnea were 63% and 41% (P < .001), for oxygen supplementation were 67% and 52% (P = .02), and for recurrent hypoxemia after oxygen supplementation were 38% and 18% (P = .01), respectively. CONCLUSIONS: Capnographic monitoring of respiratory activity improves patient safety during procedural sedation for elective ERCP/EUS by reducing the frequency of hypoxemia, severe hypoxemia, and apnea.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE: To assess the safety and efficacy of CRYO in BE with HGD. DESIGN: Multicenter, retrospective cohort study. SETTING: Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS: CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS: CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

BACKGROUND: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN: Multicenter, retrospective cohort study. SETTING: Ten academic and community medical centers between 2006 and 2009. PATIENTS: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS: Complete eradication of luminal cancer and adverse events. RESULTS: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS: Retrospective study design, short follow-up. CONCLUSIONS: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

Combined endoscopic ultrasound and secretin endoscopic pancreatic function test in patients evaluated for chronic pancreatitis.

BACKGROUND: Endoscopic ultrasound and endoscopic secretin pancreatic function test may be combined in a single endoscopic session (EUS/ePFT) to diagnose chronic pancreatitis (CP). AIMS: Our primary aim was to assess the correlation and concordance of combined EUS and secretin ePFT bicarbonate results in suspected minimal change CP. METHODS: Radial EUS included scoring for nine criteria (normal<4 criteria) with endoscopic collection of duodenal samples at 15, 30, and 45 min after secretin stimulation (normal peak bicarbonate>or=80 mmol/l). RESULTS: Three hundred and two patients completed the EUS/ePFT (252 for suspected minimal change CP, 38 for established CP, 12 for painless steatorrhea). In patients evaluated for suspected minimal change CP, a moderate negative correlation was observed between endoscopic ultrasound score and peak bicarbonate (r=-0.38, P<0.001). The EUS and ePFT results were 76% concordant and 24% discordant. The ePFT was 85% sensitive and EUS was 100% sensitive for detecting patients with established calcific CP. The EUS/ePFT diagnosed CP in two of 12 of patients evaluated for painless steatorrhea or diarrhea with weight loss. CONCLUSIONS: The combined EUS/ePFT is feasible and safe. There is only moderate correlation and concordance of endoscopic ultrasound and endoscopic pancreatic function test results in patients with suspected minimal change CP. The EUS and ePFT results produce complimentary functional and structural information for the evaluation of CP.

Safety, tolerability, and efficacy of endoscopic low-pressure liquid nitrogen spray cryotherapy in the esophagus.

Endoscopic cryotherapy is a new technique for ablation of esophageal dysplasia and neoplasia. Preliminary studies have shown it to be safe and effective for this indication. The objective of this study is to characterize safety, tolerability, and efficacy of low-pressure liquid nitrogen endoscopic spray cryotherapy ablation in a large cohort across multiple study sites. Parallel prospective treatment studies at four tertiary care academic medical centers in the U.S. assessed spray cryotherapy in patients with Barrett's esophagus with or without dysplasia, early stage esophageal cancer, and severe squamous dysplasia who underwent cryotherapy ablation of the esophagus. All patients were contacted between 1 and 10 days after treatment to assess for side effects and complications of treatment. The main outcome measurement was the incidence of serious adverse events and side effects from treatment. Complete response for high-grade dysplasia (HGD) (CR-HGD), all dysplasia (CR-D), intestinal metaplasia (CR-IM) and cancer (CR-C) were assessed in patients completing therapy during the study period. A total of 77 patients were treated for Barrett's high-grade dysplasia (58.4%), intramucosal carcinoma (16.9%), invasive carcinoma (13%), Barrett's esophagus without dysplasia (9.1%), and severe squamous dysplasia (2.6%). Twenty-two patients (28.6%) reported no side effects throughout treatment. In 323 procedures, the most common complaint was chest pain (17.6%) followed by dysphagia (13.3%), odynophagia (12.1%), and sore throat (9.6%). The mean duration of any symptoms was 3.6 days. No side effects were reported in 48% of the procedures (155/323). Symptoms did not correlate with age, gender, diagnosis, or to treatment early versus late in the patient's or site's experience. Logit analysis showed that symptoms were greater in those with a Barrett's segment of 6 cm or longer. Gastric perforation occurred in one patient with Marfan's syndrome. Esophageal stricture developed in three, all successfully treated with dilation. In 17 HGD patients, cryotherapy produced CR-HGD, CR-D, and CR-IM of 94%, 88%, and 53%, respectively. Complete regression of cancer and HGD was seen in all seven patients with intramucosal carcinoma or stage I esophageal cancer. Endoscopic spray cryotherapy ablation using low-pressure liquid nitrogen in the esophagus is safe, well-tolerated, and efficacious.

Evaluation of duct-cell and acinar-cell function and endosonographic abnormalities in patients with suspected chronic pancreatitis.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) detects mild and severe structural abnormalities of the pancreas that correlate with fibrosis. Direct pancreatic function tests (PFTs) detect mild exocrine insufficiency associated with early fibrosis. The primary aim of this study was to compare EUS structural criteria with duct-cell and acinar-cell function. METHODS: Fifty patients evaluated for chronic pancreatitis underwent combined EUS and secretin endoscopic PFTs (ePFT) on day 1 and CCK ePFT on day 2. EUS images were videotaped and interpreted by consensus of 3 blinded expert reviewers. RESULTS: There were inverse correlations of EUS consensus score with both duct-cell bicarbonate secretion (R = -0.71, P < .001) and acinar-cell lipase secretion (R = -0.52, P < .001). With secretin ePFT as reference standard, EUS (>or=4 criteria) showed a sensitivity of 71% (95% confidence interval [CI], 53%-89%) and specificity of 92% (95% CI, 75%-99%). With CCK ePFT as reference standard, EUS had a sensitivity of 63% (95% CI, 43%-82%) and specificity of 85% (95% CI, 71%-98%). Main duct dilation, irregularity, calcifications, and visible side-branches were most predictive of exocrine insufficiency (positive predictive value >80% for both acinar- and duct-cell insufficiency). CONCLUSIONS: Acinar- and duct-cell function decreases as EUS structural abnormalities increase. EUS has fair sensitivity and very good specificity compared with secretin and CCK functional reference standards.

An open-label, prospective trial of cryospray ablation for Barrett's esophagus high-grade dysplasia and early esophageal cancer in high-risk patients.

BACKGROUND: Endoscopic ablation of Barrett's esophagus (BE) is a treatment option for patients with high-grade dysplasia (HGD) and intramucosal carcinoma (IMCA). OBJECTIVE: To assess the safety and efficacy of a unique noncontact method of liquid nitrogen cryoablation as measured by histologic response rate and cancer-free survival. DESIGN: Single-center, nonrandomized cohort study. SETTING: Referral center, conducted between September 2005 and September 2008. PATIENTS: Patients with BE and HGD or IMCA who were deemed inoperable or who refused esophagectomy. Age, length of BE, and previous ablation were not exclusion criteria. INTERVENTION: Cryoablation every 6 weeks until endoscopic resolution. EMR was used for pathologic staging of nodular areas before cryoablation and focal residual areas during the follow-up period. MAIN OUTCOME MEASUREMENTS: Histologic response was defined by the worst pathology obtained at any level of the esophagus or gastric cardia in 1 of 3 categories: (1) incremental = absence of HGD and IMCA in all biopsy specimens, (2) partial = residual IMCA with absence of any dysplasia, and (3) complete = absence of any intestinal metaplasia or dysplasia. RESULTS: Thirty patients underwent ablation; 9 had undergone previous ablation or mucosectomy. Twenty-seven of 30 patients (90%) had downgrading of pathology stage after treatment. Elimination of cancer or downgrading of HGD at last follow-up was 68% for HGD and 80.0% for IMCA, with a median follow-up period of 12 months (25th percentile, 6; 75th percentile, 24). Minor adverse events included mild pain (n = 7), a low incidence of mild strictures (n = 3), and lip ulcer (n = 1). One major adverse event (perforation) in a patient with Marfan syndrome occurred with the prototype system. During follow-up, 3 of 6 patients with complete response had recurrence of dysplasia or cancer in the gastric cardia. LIMITATIONS: A nonrandomized, single-center study with a heterogeneous cohort of patients. CONCLUSIONS: Patients with BE and HGD or IMCA have a positive response to endoscopic cryotherapy at 1-year follow-up.