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Perspective on this Article from Chromoendoscopy Detects More Adenomas than Colonoscopy Using Intensive Inspection without Dye Spraying

Perspective on This Article from Microsatellite Instability and DNA Mismatch Repair Protein Deficiency in Lynch Syndrome Colorectal Polyps

Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett’s esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9 months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.

BACKGROUND AND AIMS: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM. METHODS: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression. RESULTS: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding. CONCLUSION: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding. ispartof: GASTROINTESTINAL ENDOSCOPY vol:92 issue:2 pages:259-+ ispartof: location:United States status: published

Background Endoscopic mucosal resection (EMR) allows for safe and effective removal of large non-pedunculated colon polyps. However, prior studies have shown significant recurrence rates between 10–30% after EMR, which have led to recommendations for close endoscopic follow-up and the use of techniques such as snare tip soft coagulation (STSC) to EMR margins to prevent recurrence. Models such as the Size/Morphology/Site/Access score (SMSA) have been developed to aid in identifying polyp complexity and patients at high risk of recurrence. Numerous individual risk factors for recurrence have previously been reported, however the significance of these factors have varied between studies, with limited data from Canadian centres. Aims To evaluate predictors of recurrence for large non-pedunculated polyps following EMR. Methods Consecutive patients between April 1, 2017 to March 1, 2019 who underwent EMR were retrospectively identified from endoscopy unit administrative records. Patients with non-pedunculated colorectal polyps ≥ 2 cm that were removed by EMR were included if follow-up endoscopy data were available. Polyps found to contain invasive adenocarcinoma on histology and/or were referred for surgical resection were excluded. Patient demographic, pre-procedural, intra-procedural, and post-procedural data to time of first follow-up colonoscopy were extracted. Recurrence was defined as a positive pathology specimen from the EMR scar at follow-up. Adjunctive techniques were defined as the use of any non-snare resection or ablation technique for removal of visible adenoma at the time of the EMR. Chi-square and multivariate regression analyses were conducted for variables of interest. Results 517 patients underwent large polyp EMR during the study time period with 265 patients satisfying inclusion criteria. Median age of patients was 67 years (IQR 14); 48% were female. STSC was performed to EMR margins in 94% of cases. 30.9% and 69.1% of polyps were SMSA grade 3 and grade 4 respectively. Adjunctive removal techniques were utilized in 31% of patients, 95% of which was hot avulsion. 15% of patients had recurrence on follow-up endoscopy. Higher SMSA grade was associated with the use of adjunctive techniques (20% vs. 37%, p=0.006). The use of adjunctive removal techniques (OR 2.92, p=0.007) and male gender (OR 3.45, p=0.002) were the only factors found to be significantly predictive of recurrence on multivariate analysis. Conclusions Male gender and the use of adjunctive removal techniques, particularly hot avulsion, are independently predictive of recurrence after EMR of large complex colorectal polyps. Male patients and those who require hot avulsion may be considered high risk for recurrence and warrant closer follow-up. Funding Agencies None

BACKGROUND Esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) may appear in young patients with Barrett’s esophagus (BE). However, characteristics of Barrett’s-related neoplasia in this younger population remain unknown. AIM To identify clinical characteristics that differ between young and old patients with early-stage Barrett’s-related neoplasia. METHODS We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early-stage EAC (pT1) and HGD at a tertiary-referral center between 2001 and 2017. Baseline characteristics, drug and risk factor exposures, clinicopathological staging of EAC/HGD and treatment outcomes [complete eradication of neoplasia (CE-N), complete eradication of intestinal metaplasia (CE-IM), recurrence of neoplasia and recurrence of intestinal metaplasia] were retrieved. Multivariate analyses were performed to identify factors that differed significantly between older and younger (≤ 50 years) patients. RESULTS We identified 450 patients with T1 EAC and HGD (74% and 26%, respectively); 45 (10%) were ≤ 50 years. Compared to the older group, young patients were more likely to present with ongoing gastroesophageal reflux disease (GERD) symptoms (55% vs 38%, P = 0.04) and to be obese (body mass index > 30, 48% vs 32%, P = 0.04). Multivariate logistic regression analysis showed that young patients were significantly more likely to have ongoing GERD symptoms [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.04-3.85, P = 0.04] and to be obese (OR 2.06, 95%CI 1.07-3.98, P = 0.03) whereas the young group was less likely to have a smoking history (OR 0.39, 95%CI 0.20-0.75, P < 0.01) compared to the old group. However, there were no significant differences regarding tumor histology, CE-N, CE-IM, recurrence of neoplasia and recurrence of intestinal metaplasia (mean follow-up, 44.3 mo). CONCLUSION While guidelines recommend BE screening in patients > 50 years of age, younger patients should be considered for screening endoscopy if they suffer from obesity and GERD symptoms.

Purpose: The incidence of esophageal adenocarcinoma (EAC) has increased by 700% in Western countries over the last 30 years. Although clinical guidelines call for endoscopic surveillance for EAC among high-risk populations, fewer than 5% of new EAC patients are under surveillance at the time of diagnosis. We studied the accuracy of combined cytopathology and MUC2 immunohistochemistry (IHC) for screening of Intestinal Metaplasia (IM), dysplasia and EAC, using specimens collected from the EsophaCap swallowable encapsulated cytology sponge from Canada and United States. Patients and methods: By comparing the EsophaCap cytological diagnosis with concurrent endoscopic biopsies performed on the same patients in 28 cases, we first built up the cytology diagnostic categories and criteria. Based on these criteria, 136 cases were evaluated by both cytology and MUC2 IHC with blinded to patient biopsy diagnosis. Results: We first set up categories and criteria for cytological diagnosis of EscophaCap samples. Based on these, we divided our evaluated cytological samples into two groups: non-IM group and IM or dysplasia or adenocarcinoma group. Using the biopsy as our gold standard to screen IM, dysplasia and EAC by combined cytology and MUC2 IHC, the sensitivity and specificity were 68% and 91%, respectively, which is in the range of clinically useful cytological screening tests such as the cervical Pap smear. Conclusions: Combined EsophaCap cytology and MUC2 IHC could be a good screening test for IM and Beyond.

BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.). ispartof: GASTROINTESTINAL ENDOSCOPY vol:88 issue:4 pages:647-654 ispartof: location:United States status: published

Background and study aims Accurate endoscopic detection of dysplasia in patients with Barrett’s esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. Materials and methods EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. Results Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). Conclusion We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.

Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett’s esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens. Tissue specimens were collected from four different hospitals and read by both the local pathology department (“Site diagnosis”) and a single central pathologist (“Review diagnosis”) at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed. We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%. This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.

IntroductionA 52-year-old woman presented with iron deficiency anaemia and postprandial right lower quadrant pain. Abdominal examination was unremarkable and laboratory results showed mild anaemia (haemoglobin 11.3 g/dL). Upper and lower endoscopies did not reveal any source of bleeding. Video capsule endoscopy was performed which showed a large polypoid lesion in the mid-ileum (figure 1). Abdominal contrast enhanced CT demonstrated a heterogeneously enhancing pedunculated polyp measuring approximately 6 cm (figure 2). Retrograde double-balloon enteroscopy was performed which revealed a large pedunculated polyp with hyperplastic-like mucosa protruding from a large diverticulum located approximately 70 cm proximal to the ileocaecal valve (figure 3A). The stalk appeared to arise from the base of the diverticulum (figure 3B). A technetium-99m pertechnetate scintigraphy revealed no ectopic gastric mucosa.Figure 1Video capsule endoscopy shows a large polypoid lesion.Figure 2CT shows a heterogeneously enhancing pedunculated polyp (arrow).Figure 3Retrograde double-balloon enteroscopy images. (A) Large pedunculated polyp protruding from a large diverticulum. (B) The stalk appears to arise from the base of the diverticulum.QuestionWhat is the diagnosis?

Background and study aim Both endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are used to treat Barrett’s esophagus (BE) complicated by dysplasia and intramucosal cancer. However, focal areas of BE can remain after otherwise successful application of these techniques. We report the results of hot avulsion using a hot biopsy forceps to resect these residual focal areas. Patients and methods This was a retrospective study from a prospective database in a tertiary reference center from August 2013 to May 2015. All included patients had undergone hot avulsion for eradication of residual focal areas of BE that were ≤ 1 cm and not suspicious for dysplasia, following at least one previous endoscopic treatment for dysplasia or intramucosal cancer. Results 35 patients harboring 124 residual areas of 1 – 7 mm were treated with hot avulsion. After a mean follow-up of 17.4 months, all patients achieved complete eradication of residual focal BE. One of the patients required a second hot avulsion treatment. Hot avulsion provided samples in all cases but limited the assessment of dysplasia (cautery artifact) in 20.2 % of them. The only complication was bleeding in two patients, which was easily stopped by soft coagulation. Conclusions Hot avulsion appears to be effective and safe in removing focal BE ≤ 1 cm at its greatest length remaining after endoscopic treatment for dysplasia or early cancer. Further studies are required before this technique can be considered the standard of care.

Objective: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. Methods: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. Results: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. Conclusions: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.

BACKGROUND & AIMS: Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral methylene blue formulation (MB-MMX) can be delivered directly to the colorectal mucosa. METHODS: We performed a phase 3 study of 1205 patients scheduled for colorectal cancer screening or surveillance colonoscopies (50-75 years old) at 20 sites in Europe and the United States, from December 2013 through October 2016. Patients were randomly assigned to groups given 200 mg MB-MMX, placebo, or 100 mg MB-MMX (ratio of 2:2:1). The 100-mg MB-MMX group was included for masking purposes. MB-MMX and placebo tablets were administered with a 4-L polyethylene glycol-based bowel preparation. The patients then underwent colonoscopy by an experienced endoscopist with centralized double-reading. The primary endpoint was the proportion of patients with 1 adenoma or carcinoma (adenoma detection rate [ADR]). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for differences in detection between the 200-mg MB-MMX and placebo groups. False-positive (resection rate for non-neoplastic polyps) and adverse events were assessed as secondary endpoints. RESULTS: The ADR was higher for the MB-MMX group (273 of 485 patients, 56.29%) than the placebo group (229 of 479 patients, 47.81%) (OR 1.46; 95% CI 1.09-1.96). The proportion of patients with nonpolypoid lesions was higher in the MB-MMX group (213 of 485 patients, 43.92%) than the placebo group (168 of 479 patients, 35.07%) (OR 1.66; 95% CI 1.21-2.26). The proportion of patients with adenomas ≤5 mm was higher in the MB-MMX group (180 of 485 patients, 37.11%) than the placebo group (148 of 479 patients, 30.90%) (OR 1.36; 95% CI 1.01-1.83), but there was no difference between groups in detection of polypoid or larger lesions. The false-positive rate did not differ significantly between groups (83 [23.31%] of 356 patients with non-neoplastic lesions in the MB-MMX vs 97 [29.75%] of 326 patients with non-neoplastic lesions in the placebo group). Overall, 0.7% of patients had severe adverse events but there was no significant difference between groups. CONCLUSIONS: In a phase 3 trial of patients undergoing screening or surveillance colonoscopies, we found MB-MMX led to an absolute 8.5% increase in ADR, compared with placebo, without increasing the removal of non-neoplastic lesions. Clinicaltrials.gov no: NCT01694966. ispartof: GASTROENTEROLOGY vol:156 issue:8 pages:2198-+ ispartof: location:United States status: published

Clinicians can be forgiven for thinking of anisakiasis as a rare condition low in the differential diagnosis of abdominal pain. Gastrointestinal anisakiasis is a zoonotic parasitic disease caused by consumption of raw or undercooked seafood infected with nematodes of the genusAnisakis. Even though the reported cases indicate that this is a rare disease, the true incidence of the disease could be potentially higher than what is reported in the literature as cases can go undiagnosed. Diagnosis and treatment of gastric anisakiasis are made by a compatible dietary history, direct visualization, and removal of the larvae via gastroscopy. Serologic testing and imaging studies are useful in the diagnosis of intestinal anisakiasis and conservative management should be considered. This disease may mimic other diseases and lead to unnecessary surgery. This emphasizes the importance of suspecting gastrointestinal anisakiasis by history taking and by other diagnostic modalities.

We evaluated diffuse reflectance spectroscopy implemented as a small field-of-view technique for discrimination of dysplasia from metaplasia in Barrett’s esophagus as an adjuvant to autofluorescence endoscopy. Using linear discriminant analysis on 2579 spectra measured in 54 patients identified an optimum a 4-wavelength classifier (at 485, 513, 598 and 629 nm). Sensitivity and specificity for a test data set were 0.67 and 0.85, respectively. Spectroscopic results show that this technique could be implemented in wide-field imaging mode to improve the accuracy of existing endoscopy techniques for finding early pre-malignant lesions in Barrett’s esophagus. Results show that the discrimination occurs likely due to redistribution of blood content in the tissue sensed by the optical probing with the wavelength-dependent sampling depth. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The galactose oxidase-Schiff (GOS) reaction detects D-galactose-β-[1,3]-N-acetyl-D-galactosamine. This is a T-antigen expressed in mucus from malignant cells and colonic mucosa adjacent to cancer but not in normal mucosa. Previous studies using a qualitative GOS assay proved to be of limited value for the detection of colorectal neoplasia. We used a newly developed quantitative GOS assay to determine its potential as an early detection biomarker for colorectal cancer. We completed a multi-center, prospective, cross-sectional cohort validation study consisting of 70 normal controls, 23 high-risk normal patients (polyp history or family history of colorectal cancer (CRC) with currently normal colonoscopy), 137 patients with adenomatous polyps, and 69 with colorectal cancers. Prior to colonoscopy, two samples of stool were collected via a rectal exam: one for FOBT, and one for GOS. The area under the ROC curve (AUC) for detecting colonic adenomas and cancer for normal colons, computed with logistic regression was 0.69 for GOS, 0.62 for FOBT, and 0.73 for GOS combined with FOBT. Adding GOS to FOBT did not significantly change the ROC of FOBT alone. GOS does not appear to be a suitable marker of colorectal neoplasia.

Although the efficacy and safety of extensive endomucosal resection (EMR) in eradicating Barrett’s esophagus (BE) harbouring early neoplasia have been established, factors predicting efficacy remains unclear. To determine the complete eradication rate of Barrett’s esophagus with high-grade intraepithelial neoplasia (HGIN) or intramucosal carcinoma (IMC), safety, and factors predicting complete eradication by EMR. Patients with histological confirmation of Barrett’s HGIN/IMC were prospectively identified. EMR was performed using Duette multiband ligator or cap technique by a single operator (NEM). 99 patients (81 males) with median age 67 years [interquartile range (IQR) 60–77 years] and median Barrett’s length 4 cm (IQR 2–6 cm) were included. Of 628 index EMRs [mean 6.3, median 5 (IQR 3–8)], 23% showed IMC, 58.5% showed HGIN, and 16% showed low-grade dysplasia only. A median of 8 EMR resections per patient (IQR 6–16, 1,064 resections in 89 patients) resulted in complete eradication of BE harboring neoplasia in 49.4% and eradication of HGIN/IMC in 81% (BE

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) remains a challenge for endoscopists in patients with surgically altered anatomy of the upper gastrointestinal tract. Double-balloon enteroscopes (DBEs) have revolutionized the ability to access the small bowel. The indication for its therapeutic use is expanding to include ERCP for patients who have undergone small bowel reconstruction. Most of the published experiences in DBE-assisted ERCP have used conventional double-balloon enteroscopes that are 200 cm in length, which do not permit use of the standard ERCP accessories. The authors report their experience with DBE-assisted ERCP using a ‘short’ DBE in patients with surgically altered anatomy.METHODS: A retrospective review of patients with previous small bowel reconstruction who underwent ERCP with a ‘short’ DBE at the Centre for Therapeutic Endoscopy and Endoscopic Oncology (Toronto, Ontario) between February 2007 and November 2008 was performed.RESULTS: A total of 20 patients (10 men) with a mean age of 57.9 years (range 26 to 85 years) underwent 29 sessions of ERCP with a DBE. Six patients underwent Billroth II gastroenterostomy, seven patients Roux-en-Y hepaticojejunostomy, five patients Roux-en-Y gastrojejunostomy, one patient Roux-en-Y esophagojejunostomy and one patient a Whipple’s operation with choledochojejunostomy. Some patients (n=12 [60%]) underwent previous attempts at ERCP in which the papilla of Vater or bilioenteric anastomosis could not be reached with either a duodenoscope or pediatric colonoscope. All procedures were performed with a commercially available DBE (working length 152 cm, distal end diameter 9.4 mm, channel diameter 2.8 mm). The procedures were performed under conscious sedation with intravenous midazolam, fentanyl and diazepam, except in one patient in whom general anesthesia was administered. Either the papilla of Vater or bilioenteric anastomosis was reached in 25 of 29 cases (86.2%) in a mean duration of 20.8 min (range 5 min to 82 min). Bile duct cannulation was successful in 24 of 25 cases in which the papilla or bilioenteric anastomosis was reached. Therapeutic interventions were successful in 15 patients (24 procedures) including sphincterotomy (n=7), stone extraction (n=9), biliary dilation (n=8), stent placement (n=9) and stent removal (n=8). The mean total duration of the procedures was 70.7 min (range 30 min to 117 min). There were no procedure-related complications.CONCLUSION: DBEs enable successful diagnostic and therapeutic ERCP in patients with a surgically altered anatomy of the upper gastrointestinal tract. It is a safe, feasible and less invasive therapeutic option in this group of patients. Standard ‘long’ DBEs have limitations of long working length and the need for modified ERCP accessories. ‘Short’ DBEs are equally as effective in reaching the target limb as standard ‘long’ DBEs, and overcomes some limitations of long DBEs to result in high success rates for endoscopic therapy.

Esophageal lichen planus is a rare condition, and although the majority of cases occur in conjunction with lichen planus at other sites, the endoscopic features are often misinterpreted resulting in a delay in diagnosis. We report a series of five patients presenting to our unit between 2005 and 2009. All five patients were female and presented with dysphagia. Endoscopy demonstrated proximal esophageal stricturing in four patients. Characteristic histological findings were found in four patients. Lichen planus was diagnosed at other sites, and preceded gastrointestinal symptoms, in all patients; five had oral involvement, two had genital involvement, and one had dermal involvement. All patients received proton pump inhibitor therapy without demonstrable benefit. Administration of oral fluticasone proprionate resulted in symptomatic improvement in three patients.

Cryotherapy is a novel endoscopic method of ablating abnormal gastrointestinal (GI) mucosa with cryogens originating from either liquid nitrogen or carbon dioxide gas. The ablation is performed by passing a catheter through the accessory channel of an endoscope and the cryogen is sprayed onto the target tissue in a noncontact manner. Cell death is induced by producing extracellular ice. Recently, several reports have been published on the efficacy of cryotherapy for clinical use in the GI tract. In Barrett's esophagus, reports describe that cryotherapy was effective to eradicate or downgrade Barrett's associated dysplasia. Cryotherapy has also been reported to be useful for palliation of squamous cell carcinoma. Chronic recurrent bleeding from watermelon stomach (gastric antral vascular ectasia [GAVE]) and radiation-induced proctitis have also been found responsive to cryotherapy. Although based on results with relatively small numbers of patients and short follow-up periods, cryotherapy has been demonstrated to be safe and effective. This is a promising technology that will require multicenter controlled trials to better define its role as an effective and alternative form of tissue ablation.

Background and Aims: Accurate endoscopic detection of premalignant lesions and early cancers in the colon is essential for cure, since prognosis is closely related to lesion size and stage. Although it has great clinical potential, autofluorescence endoscopy has limited tumor-to-normal tissue image contrast for detecting small preneoplastic lesions. We have developed a molecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate which targets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescence-based endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T) subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivo whole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology. Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours post injection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstrated that modification of CC49 antibodies did not alter their specific tumor-localizing properties, and was antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probe targeting a tumor-associated mucin detects colonic tumors at the molecular level in real time, and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

Background: Folate deficiency increases the risk of several human diseases. Likewise, high intakes of folate, particularly synthetic folic acid intake, may be associated with adverse health outcomes in humans. A more comprehensive understanding of the ‘‘input side’’ of folate nutrition may help to set dietary recommendations that strike the right balance between health benefits and risks. It is well known that the microflora in the colon produce large quantities of folate that approach or exceed recommended dietary intakes; however, there is no direct evidence of the bioavailability of this pool in humans. Objective: The objective was to determine whether, and to what extent, the natural folate vitamer 5-formyltetrahydrofolic acid is absorbed across the intact colon of humans. Design: During screening colonoscopy, 684 nmol (320 lg) [ 13 C]glutamyl-5-formyltetrahydrofolic acid was infused directly into the cecum of 6 healthy adults. Three or more weeks later, each subject received an intravenous injection of the same compound (172 nmol). Blood samples were collected before and after each treatment. The ratio of labeled to unlabeled folates was determined in plasma by tandem mass spectrometry. Results: The apparent rate of folate absorption across the colon of a bolus dose of [ 13 C]5-formyltetrahydrofolic acid infused into the cecum was 0.6 6 0.2 nmol/h, as determined by the appearance of [ 13 C5]5-methyltetrahydrofolic acid in plasma. In comparison, the rate of appearance of [ 13 C5]5-methyltetrahydrofolic acid after an intravenous injection of [ 13 C5]5-formyltetrahydrofolate was 7 6 1.2 nmol/h. Conclusion: Physiologic doses of natural folate are absorbed across the intact colon in humans. Am J Clin Nutr 2009;90:116‐23.

BACKGROUND: There is no consensus on the relative accuracy of capsule endoscopy (CE) versus double-balloon enteroscopy (DBE) to investigate obscure gastrointestinal bleeding (GIB). CE is less invasive, but DBE more directly examines the small bowel, and allows tissue sampling plus therapeutic intervention.OBJECTIVES: To evaluate the yield and outcome of DBE following CE in patients with obscure GIB.METHODS: After DBE became readily available at the Centre for Therapeutic Endoscopy and Endoscopic Oncology (St Michael’s Hospital, Toronto, Ontario), all patients with obscure GIB seen from December 2002 to June 2007 were evaluated identically, first with CE, then with DBE (some with further interventions). Findings, adverse outcomes and interventions are reported.RESULTS: Fifty-one patients (25 women) with a mean (range) age of 64.1 years (34 to 83 years) are reported. Eight patients underwent DBE twice, for a total of 59 DBEs. Fourteen patients had overt GIB and the median (range) number of red blood cell unit transfusions was 10 (0 to 100). The positive findings for each type of lesion were compared in these 51 patients: angiodysplasia (CE 64.7% and DBE 61%, P=0.3), ulcers (CE 19.6% and DBE 18.6%, P=0.5), bleeding lesions (CE 43.1% and DBE 15.3%, P=0.0004) and mass (CE 10.2% and DBE 8.5%, P=0.5). DBE provided the advantage of therapeutic intervention: argon plasma coagulation (33 of 59 DBEs), clipping (two of 59), both argon plasma coagulation and clipping (three of 59), polypectomy (two of 59), tattooing (52 of 59) and biopsies (11 of 59). DBE detected lesions not seen by CE in 21 patients; lesions were treated in 18 patients. However, CE detected 31 lesions not seen by DBE. No major complications occurred with either examination.CONCLUSION: Overall detection rates for both techniques are similar. Each technique detected lesions not seen by the other. These data suggest that CE and DBE are complementary and that both evaluate obscure GIB more fully than either modality alone.

Endoscopic band ligation (EBL) is the most effective and accepted treatment for acute esophageal variceal bleeding (1). EBL is an easy and safe method to achieve hemostasis for gastrointestinal (GI) bleeding, in contrast to other endoscopic therapies (thermal, mechanical, injection). The use of EBL for other types of bleeding in the GI tract has been published mostly as case report series (Table 1). In the present review, we describe the results of published studies that have evaluated different options for EBL in the setting of nonvariceal bleeding. TABLE 1 Different options for endoscopic band ligation in nonvariceal bleeding

Early identification of dysplasia remains a critical goal for diagnostic endoscopy since early discovery directly improves patient survival because it allows endoscopic or surgical intervention with disease localized without lymph node involvement. Clinical studies have successfully used tissue autofluorescence with conventional white light endoscopy and biopsy for detecting adenomatous colonic polyps, differentiating benign hyperplastic from adenomas with acceptable sensitivity and specificity. In Barrett's esophagus, the detection of dysplasia remains problematic because of background inflammation, whereas in the squamous esophagus, autofluorescence imaging appears to be more dependable. Point fluorescence spectroscopy, although playing a crucial role in the pioneering mechanistic development of fluorescence endoscopic imaging, does not seem to have a current function in endoscopy because of its nontargeted sampling and suboptimal sensitivity and specificity. Other point spectroscopic modalities, such as Raman spectroscopy and elastic light scattering, continue to be evaluated in clinical studies, but still suffer the significant disadvantages of being random and nonimaging. A recent addition to the fluorescence endoscopic imaging arsenal is the use of confocal fluorescence endomicroscopy, which provides real-time optical biopsy for the first time. To improve detection of dysplasia in the gastrointestinal tract, a new and exciting development has been the use of exogenous fluorescence contrast probes that specifically target a variety of disease-related cellular biomarkers using conventional fluorescent dyes and novel potent fluorescent nanocrystals (i.e., quantum dots). This is an area of great promise, but still in its infancy, and preclinical studies are currently under way.

Accurate endoscopic detection and dysplasia in patients with Barrett’s esophagus (BE) remains a major unmet clinical need. Current diagnosis use multiple biopsies under endoscopic image guidance, where up to 99% of the tissue remains unsampled, leading to significant risk of missing dysplasia. We conducted an ex vivo clinical trial using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) with known high-grade dysplasia for the purpose of characterizing the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia det ection and therapeutic guidance. EMR tissues were mounted immediately on an agar layer and covered with ultras ound gel. Digital photography guided the placement of the PAI transducer (40 MHz center frequency). The luminal side of the specimen was scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, 824, 850 and 970 nm. Acoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with H&E staining. Analysis consisted of co-registration and correlation between the intrinsic PAI features and the histological images. The initial PAI + ultrasound images from 8 BE patients have demonstrated the technical feasibility of this approach and point to the potential of PAI to reveal the microvascular pattern within EMR specimens. There are several technical factors to be considered in rigorous interpretation of th e PAI characteristics, includin g the loss of blood from the ex vivo specimens and the limited depth penetration of the photoacoustic signal. Keywords: Photoacoustic imaging, cancer, diagnostics, endoscopic mucosal resection, Barrett’s esophagus, gastrointestinal imaging, dysplasia

Background Appendiceal mucoceles are uncommon cystic neoplasms characterized by distension of the appendiceal lumen with mucus. There have been no reported series of colonoscopically diagnosed mucoceles with clinicopathologic correlation. Methods A retrospective review of colonoscopies performed at our institution over the past 14 years was undertaken with patient demographics, clinical data, surgical outcomes, and histopathology obtained from hospital records. Observations Seven patients (6 women) with mucocele of the appendix were identified at colonoscopy. Three had complained of right lower quadrant pain. All 7 patients underwent surgical resection. Histopathology demonstrated mucinous cystadenoma in all. No cases revealed carcinoma, and there have been no deaths related to the mucocele. Conclusions Appendiceal mucoceles may be recognized at colonoscopy as a smooth bulbous submucosal lesion of the cecum with an impression formed by the appendiceal orifice. Recognition at colonoscopy is important because it enables accurate diagnosis and directs management. Surgery is recommended in all cases given the risk of malignancy or perforation with resultant pseudomyxoma peritonei.