Persistent Low-grade Dysplasia Research Articles

The role of multiple high-risk human papillomavirus infections for cervical biopsies and findings in colposcopic procedures

The clinical outcome of high-risk HPV (hr-HPV) infection varies according to genotype(s). Patients may harbor either one single hr-HPV (s-HPV) or multiple HPV (m-HPV) genotypes. Recently, the relationship between m-HPV infections and high-grade dysplasia has been investigated, and controversial results have been obtained. Therefore, the clinical significance of m-HPV is not clear. This study aimed to evaluate which group is associated with higher grade dysplasia by analyzing colposcopic punch biopsies. A total of 690 patients who were scheduled for a diagnostic excisional procedure between April 2016 and January 2019 due to the detection of high-grade cervical intraepithelial neoplasia (CIN 2/3) in colposcopy were included. Patients who were not scheduled for colposcopic examination or cervical punch biopsy, or who were scheduled for an excisional procedure due to smear-biopsy incompatibility or persistent low-grade dysplasia were excluded. Patients with a negative HPV test and an unknown HPV genotype were also excluded. Among the patients scheduled for excision (n=404), 74.5% had a s-HPV and 25.5% had a m-HPV infection. The proportion of CIN 1, 2 and 3 per patient in the m-HPV group was significantly higher than the s-HPV group (p=0.017). When this analysis was made for the number of CIN 2+3 per patient in the s-HPV and m-HPV groups, it was 1.29 (389/301) and 1.36 (140/103), respectively, and no difference was found (p=0.491). Patients in the m-HPV group, who underwent more colposcopic cervical biopsies, had higher numbers of CIN lesions, regardless of age and cytology results.

Endoscopic full-thickness resection of gastric ulceration with persistent low-grade dysplasia using full-thickness resection device.

Video 1Endoscopic full-thickness resection of gastric ulceration with persistent low-grade dysplasia using full-thickness resection device.

S359 Endoscopic Full-Thickness Resection of Gastric Ulceration with Persistent Low-Grade Dysplasia Using the Full-Thickness Resection Device

Introduction: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established treatment methods for resection of precancerous gastric lesions and early gastric cancers. Ulcerated or scarred gastric lesions are challenging to resect with EMR or ESD due to submucosal fibrosis and scarring, and hence, carry an increased risk for perforation. Endoscopic full-thickness resection (EFTR) using the full-thickness resection device (FTRD) is rapidly gaining popularity for the treatment of upper gastrointestinal tract lesions. While it has been shown to be a safe and effective treatment modality for colorectal lesions not amenable to conventional resection methods, data regarding its use in the upper GI tract is evolving. Here, we describe a patient with an ulcerated gastric lesion with persistent low-grade dysplasia who underwent successful resection of the lesion using the FTRD. Case Description/Methods: A 75-year-old man with a history of diffuse gastric intestinal metaplasia was found to have a 1 cm ulcer in the gastric antrum (Figure A). Biopsies of the ulcer demonstrated low-grade dysplasia, while surrounding biopsies showed incomplete gastric intestinal metaplasia. He was started on a proton pump inhibitor with plan for repeat endoscopy for surveillance. Subsequent upper endoscopy 12 and 24 months later showed partial healing of the gastric ulcer (Figure B), however, biopsies showed persistent low-grade dysplasia. After a multidisciplinary discussion, the decision was made to pursue EFTR of the ulcerated lesion. An upper endoscopy was performed and the borders of the lesion were marked circumferentially with a marking probe. The FTRD was mounted on a modified therapeutic upper endoscope and the lesion was resected. The resection site was examined and demonstrated appropriate positioning of the clip and no evidence of bleeding (Figure C). Given the proximity of the lesion to the pylorus, the endoscope was advanced to the duodenum documenting luminal patency. The patient tolerated the procedure well and was discharged the same day. No adverse events were experienced within four weeks of the procedure. The final pathology report of the lesion confirmed focal low-grade dysplasia (Figure D) with negative resection margins (R0). Discussion: EFTR using the FTRD device can offer a safe and effective approach to treat ulcerated or scarred gastric lesions that are not typically amenable to conventional endoscopic resection techniques. Watch the video at https://tinyurl.com/ACGAbstractS359Figure 1.: A) Initial upper endoscopy with antral gastric ulcer. B) Subsequent upper endoscopy showing partial healing of the gastric ulcer. C) Endoscopic view of the resection site with overlying clip after EFTR. D) Pathology of resected lesion demonstrating focal low-grade dysplasia.

Indications, contraindications and limitations of endoscopic therapy for Barrett's esophagus and early esophageal adenocarcinoma.

Endoscopic eradication therapy (EET) has revolutionized management of Barrett’s esophagus (BE)-associated neoplasia, traditionally treated by esophagectomy, which carries very high mortality and morbidity. EET, usually performed in the outpatient setting, has a safe risk profile. It is indicated in patients with BE with high-grade dysplasia and intramucosal cancer, confirmed, and persistent low-grade dysplasia, and in highly selected cases of non-dysplastic BE and submucosal cancers. Multiple EET modalities are available and can be categorized into two groups: ablation therapies and resection techniques with resection techniques usually reserved for nodular/raised lesions or lesions with suspected neoplasia. Patients usually require multiple ablation sessions with a goal of achieving complete eradication of metaplasia. Despite very good results, EET has its limitations and is not 100% effective: it targets a small subset of patients along the spectrum of BE and esophageal adenocarcinoma, as most patients with esophageal adenocarcinoma remain asymptomatic until the disease has progressed to advanced stages. Post-ablation surveillance is mandatory, as recurrences are common. An area of concern is buried metaplasia reported to occur following ablation therapy and thought to be from de novo growth of metaplastic tissue underneath the neosquamous epithelium, following ablation. The focus of this review article is to present the indications, contraindications and limitations of EET.

AGA Clinical Practice Update on Endoscopic Treatment of Barrett’s Esophagus With Dysplasia and/or Early Cancer: Expert Review

The purpose of this best practice advice article is to describe the role of Barrett's endoscopic therapy (BET) in patients with Barrett's esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients. The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee. BEST PRACTICE ADVICE 1: In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3-6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection. BEST PRACTICE ADVICE 2: Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia. BEST PRACTICE ADVICE 3: BET is the preferred treatment for BE patients with high-grade dysplasia (HGD). BEST PRACTICE ADVICE 4: BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a). BEST PRACTICE ADVICE 5: BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-μm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates. BEST PRACTICE ADVICE 6: In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5-10 mm proximal to the squamocolumnar junction and 3) 5-10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion. BEST PRACTICE ADVICE 7: Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities. BEST PRACTICE ADVICE 8: BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually. BEST PRACTICE ADVICE 9: BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies. BEST PRACTICE ADVICE 10: If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation. BEST PRACTICE ADVICE 11: Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy. BEST PRACTICE ADVICE 12: When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%. BEST PRACTICE ADVICE 13: After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years. BEST PRACTICE ADVICE 14: Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia. BEST PRACTICE ADVICE 15: The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation. BEST PRACTICE ADVICE 16: Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.

935 Salvage Hybrid APC After Failed Radiofrequency Ablation and Cryotherapy for Barrett’s Esophagus

INTRODUCTION: The frequency of Barrett’s esophagus (BE) has increased by a factor of more than 7 during the past four decades in the United States. It has been estimated that 5.6 percent of adults in the United States have Barrett's esophagus, although the large majority of cases go unrecognized. Endoscopic resection of visible lesions, followed by ablation of the rest of the BE epithelium is the current standard of care for management of BE with confirmed dysplasia and IMC. Today, the most readily use treatment for Barret’s esophagus is RFA and APC. None of the current methods are able to guarantee a complete ablation success of 100 %. Cryotherapy has become a salvage technique for patient that have failed RFA. There is limited data available to determine the efficacy and safety of this technique. For patients who failed RFA and Cryotherapy, there are limited options available. The aim of this study is to assess the efficacy and safety of hybrid APC in patients with BE dysplasia who failed RFA and cryotherapy.Hybrid APC can be an effective alternative adjunctive salvage tool to RFA and cryotherapy for patients in whom both of these techniques have failed. METHODS: This is a single center, retrospective cohort study at a tertiary medical center between 2010 and 2019 in patients with BE low-grade dysplasia (LGD) and high grade dysplasia (HGD) who failed RFA and cryotherapy treatment. Six patients with an average age of 63, and five out of six are males (84%) and five have persistent LGD (84%). Response was determined by complete eradication (CE). Six patients with persistent dysplasia and with incomplete response to RFA and cryotherapy were offered hybrid APC. The primary endpoint was CE after hybrid APC. RESULTS: A total of 6 patients underwent RFA and Cryotherapy for BE dysplasia. After an average of 4.5 RFA sessions and 2.7 Cryotherapy session none of the patient were able to reach CE. 5 patients with BE with LGD and 1 with HGD were offered H-APC after failure of reaching CE (average of 2.3 H-APC treatment). CE was reached in 100% of the patients who underwent H-APC. 6 months endoscopic surveillance has not shown any recurrence of BE or dysplasia. CONCLUSION: Patient with refractory dysplasia or recurrent dysplasia after failed eradication of salvage cryotherapy and radiofrequency ablation were offered hybrid APC. The data demonstrate a complete eradication in those patients who failed treatment with RFA and cryotherapy. Furthermore, there were no alternative outcome reported as of to date.

Persistent confirmed low-grade dysplasia in Barrett's esophagus is a risk factor for progression to high-grade dysplasia and adenocarcinoma in a US Veterans cohort.

Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24-5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61-13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83-6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03-17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

FA02.05: PROGRESSION RATE OF BARRETT’S ESOPHAGUS FROM NATIONAL REGISTRY OF EXPERT CENTERS IS MUCH GREATER THAN ANTICIPATED FROM POPULATION STUDIES

Abstract Background Barrett's Esophagus (BE) is well established as the main pathological precursor for esophageal adenocarcinoma (EAC). Progression to high grade dysplasia (HGD) or EAC varies widely between population based studies and specialized BE registries from high volume centers. No such data existed from the Republic of Ireland until 2011 when a multicenter registry was established involving three centers to more accurately determine the risk of progression to EAC in the Irish population. Methods A detailed clinical, endoscopic and pathological database includes 3397 patients from January 2008 to July 2017, with BE defined by the presence of specialized intestinal metaplasia (SIM). A prospective web based database was used to gather information from three designated esophageal centers with initial and follow up data abstracted by a data manager and overseen by a project manager. Results 325 were excluded following a diagnosis of HGD or EAC at index biopsy, or being a tertiary referral, leaving 3072 with a median age of 61 and a 2.1:1 male to female ratio and a median follow up of 3 years, and 5024 person years. 127 (4%) cases progressed to HGD/EAC, 65 after one year of follow up. 55 (2%) developed EAC were identified, 30 of those within one year. The overall incidence HGD/EAC was 2.53% per year, 1.3% if the first year is excluded. The risk of progression to EAC alone was 1.09% per year, 0.5% excluding the first year. Low grade dysplasia (LGD) on index biopsy was associated with a progression rate of 11.7% per year, 4.2% with the first year excluded. Conclusion With strict data entry and pathologic quality assurance, progression rates for non-dysplastic BE was several fold higher than population studies, highlighting caution in abstracting from population data. True LGD, as evidenced in a recent report by Kestens et al.1 represent high risk disease, with most of the risk evident within the first year. Reference: 1. Kestens C, Offerhaus G, van Baal J, Siersema PD. Patients wtih Barrett's esophagus and persistent low-grade dysplasia have an increased risk for high- grade dysplasia and cancer. Clin Gastroenterol Hepatol. 2016;14:956–962 Disclosure All authors have declared no conflicts of interest.

Patients With Barrett’s Esophagus and Confirmed Persistent Low-Grade Dysplasia Are at Increased Risk for Progression to Neoplasia

For patients with Barrett's esophagus, the diagnosis of low-grade dysplasia (LGD) is subjective, and reported outcomes vary. We analyzed data from a multicenter study of endoscopic therapy to identify factors associated with progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with LGD of the esophagus. We performed a retrospective analysis of data from 255 patients with a primary diagnosis of LGD (78% men; mean age, 63 years) who participated in a randomized controlled trial of surveillance vs radiofrequency ablation in Europe. Three expert pathologists independently reviewed baseline and subsequent LGD specimens. The presence and degree of dysplasia was separately recorded for each biopsy and classified according to the Vienna Classification system. The primary end point was development of HGD or EAC. We performed univariate logistic regression analyses to assess the association between outcomes and factors such as number of pathologists confirming LGD, multifocality of LGD, and persistence of LGD over time. Of the 255 patients, 45 (18%) developed HGD or EAC during a median 42-month follow-up period (interquartile range, 25-61 months); patients were examined by a median 4 endoscopies (interquartile range, 3-6 endoscopies). The number of pathologists confirming LGD was strongly associated with progression to neoplasia; risk for progression increased greatly when all 3 pathologists agreed onLGD (odds ratio, 47.14; 95% confidence interval, 13.10-169.70). When LGD was detected at baseline and confirmed by a subsequent endoscopy, the odds for progression to neoplasia also increased greatly (odds ratio, 9.28; 95% confidence interval, 4.39-19.64). Multifocal LGD was not significantly associated with progression to neoplasia. The number of pathologists confirming LGD and persistence of LGD over time increase risk for development of HGD or EAC in patients with Barrett's esophagus and LGD. These simple, readily available variables can help stratify risk and select patients for prophylactic ablation therapy.

Patients With Barrett's Esophagus and Persistent Low-grade Dysplasia Have an Increased Risk for High-grade Dysplasia andCancer.

In some patients with Barrett's esophagus (BE) and a confirmed diagnosis of low-grade dysplasia (LGD), the LGD is not detected during follow-up examinations. We would like to avoid the unnecessary risks and costs of ablative treatment for these patients. Therefore, we investigated whether persistent LGD increases risk for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and what proportion of patients are no longer found to have dysplasia after an initial diagnosis of LGD. In a retrospective study, we collected information on 1579 patients with BE and LGD from 2005 through 2010 by using a nationwide registry of histopathology diagnoses in the Netherlands (PALGA). Confirmed LGD was defined as a diagnosis of LGD that was confirmed by any other pathologist. Persistent LGD was defined as LGD detected at the first and follow-up endoscopy. Datawere collected on patients until treatment for HGD, detection of EAC, or the last endoscopy at which a biopsy was collected (through July 2014). We evaluated whether persistent LGD was a risk factor for malignant progression by using univariable and multivariable Cox regression analyses. Of individuals with BE and LGD in the database, the diagnosis of LGD was confirmed for 161 patients (10% of total). In these patients, the incidence of HGD and/or EAC was 5.18/100 person-years (95% confidence interval [CI], 4.32-8.10/100 person-years) compared with 1.85/100 person-years (95% CI, 1.52-2.22/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. The incidence of EAC alone in patients with confirmed LGD was 2.51/100 person-years (95% CI, 1.46-3.99/100 person-years), compared with 1.01/per 100 person-years (95% CI, 0.41-2.10/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. Of patients in whom LGD was confirmed at the first endoscopic examination, 51% were not found to have dysplasia at the first follow-up endoscopy, and 30% had persistent LGD. In patients with persistent LGD, the incidence of HGD and/or EAC was 7.65/100 person-years (95% CI, 4.45-12.34) and of only EAC was 2.04/100 person-years (95% CI, 0.65-4.92); in patients without persistent LGD, the incidence of HGD and/or EAC was 2.32/100 person-years (95% CI, 1.08-4.40/100 person-years) and of only EAC was 1.45 (95% CI, 0.53-3.21/100 person-years). Persistent LGD was found to be an independent risk factor for the development of HGD and/or EAC, with hazard ratio of 3.5 (95% CI, 1.48-8.28). In a large population-based cohort study of patients with BE and LGD, the risk of progression to HGD and/or EAC was higher in patients with confirmed LGD and highest in those with confirmed and persistent LGD.

Enfermedades esofágicas: enfermedad por reflujo gastroesofágico, Barrett, acalasia y esofagitis eosinofílica

The most important novel findings presented on oesophageal disease in DDW 2015 were the following: 1) GERD: a) hypervigilance seems to be a key pathogenic factor in reflux symptoms refractory to PPI; b) post-reflux swallowing-induced peristaltic waves could be an excellent diagnostic criterion for GERD; c) laryngeal pH-metry is not useful in the diagnosis of extra-oesophageal symptoms; d) the recommendation of weight loss adequately recorded in the clinical reports of patients with GERD and obesity or overweight is an excellent quality indicator and is associated with better outcomes. 2) Barrett's oesophagus: a) persistent low-grade dysplasia in more than one endoscopy and a diagnosis of “indefinite for dysplasia” are associated with a high risk of neoplastic progression; b) narrow-band imaging allows areas of dysplasia on Barrett's oesophagus to be identified with high sensitivity and specificity; c) initial endoscopy fails to identify a high percentage of advanced neoplasms in Barrett's oesophagus. Early re-endoscopy should be considered; d) endoscopists specialized in Barret's oesophagus obtain a much higher yield in the diagnosis of advanced lesions. Patients at high risk–men, older patients, smokers and those with long-segment Barrett's oesophagus–could benefit from follow-up in a referral center. 3) Achalasia: POEM seems safe and effective, independently from patient characteristics (age, comorbidity) and the technical variations used. 4) Eosinophilic esophagitis: topical budesonide and exclusion diets are reasonably effective in PPI non-responders.

52 Persistent Low-Grade Dysplasia in Barrett's Esophagus Identifies Patients at Higher Risk for Esophageal Adenocarcinoma: A Dutch Nationwide Cohort Study

52 Persistent Low-Grade Dysplasia in Barrett's Esophagus Identifies Patients at Higher Risk for Esophageal Adenocarcinoma: A Dutch Nationwide Cohort Study

Morphology and natural history of familial adenomatous polyposis-associated dysplastic fundic gland polyps

Most patients with familial adenomatous polyposis (FAP) develop gastric fundic gland polyps, with many displaying low-grade dysplasia. This study evaluates the natural history and morphological phenotype of dysplasia in FAP-associated fundic gland polyps. Patients with FAP and dysplastic fundic gland polyps (n = 24) were identified. Twenty-two of 24 FAP-associated dysplastic fundic gland polyps showed a gastric phenotype and two had mixed phenotype. During a mean 6.1-year follow-up (range 0.8-12.6 years) and 5.7 endoscopies (range 2-22), one patient (4%) was diagnosed with a fundic gland polyp with high-grade dysplasia, while 23 patients (96%) in this cohort had either no dysplasia or persistent low-grade dysplasia. Contemporary patients with sporadic fundic gland polyps with low-grade dyplasia had similar morphology and outcomes to the FAP-associated fundic gland polyp cohort. Dysplasia in fundic gland polyps (FAP-associated and sporadic) was associated less frequently with intestinal phenotype, high-grade dysplasia and the finding of concurrent or subsequent carcinoma compared to contemporary patients with sporadic gastric dysplasia not occurring in fundic gland polyps. This cohort of patients with FAP-associated dysplastic fundic gland polyps rarely developed high-grade dysplasia and gastric adenocarcinoma was absent.

The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary sclerosing cholangitis colitis before and after liver transplantation

Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) alters neoplasia progression. To examine the natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that develop in patients with PSC-UC with and without LT. We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7], while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3; 95% CI, 0.1-0.9). In PSC-UC patients with IND, 5-ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.

Predictors of Colorectal Neoplasia Outcomes in Indefinite and Low-Grade Dysplasia in Patients with Primary Sclerosing Cholangitis and Ulcerative Colitis: ACG IBD Research Award

Purpose: Patients (pts) with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk for colorectal neoplasia. We sought to examine the natural history of low-grade dysplasia (LGD) and indefinite dysplasia (IND) in order to identify factors associated with neoplasia progression or persistence in pts with PSC-UC. Methods: We performed a retrospective review of pts with PSC and UC who were diagnosed with LGD or IND (index lesion confirmed after review by a pathologist). LGD was classified as unifocal or multifocal and flat or raised. Raised lesions in an area of colitis were considered adenoma-like dysplasia (ALD). Sporadic adenomas were excluded. Pts were excluded if they had a prior colectomy, colorectal neoplasia, or liver transplant (LT) or did not follow up beyond 60 days of their index lesion. Pts were censored at the time of colectomy, last colonoscopy or LT, whichever was earliest. The primary end-point was neoplasia progression, or persistent LGD. Covariates were included into the multivariate model if they had a p-value of ≤0.05 in the univariate analysis. Results: Sixty-three pts (IND n=47, LGD n=16) were followed for 176 pt-years. The primary endpoint was reached in 56% of pts with LGD [cancer n=1; persistent LGD (multifocal n=2; ALD n=6)] and in 28% with IND (cancer n=3; HGD n=3; multifocal LGD n=2; ALD LGD n=1; flat LGD n=4). Compared to those with IND, pts with LGD were older (57 years versus 42 years, p<0.01), and had a longer duration of UC (28 years versus 10 years, p=0.03) and PSC (9 years versus 6 years, p=0.05). Compared to LGD, IND lesions were more likely to be flat (98% versus 50%, p<0.01) and found in an area of colitis (100% versus 81% p<0.01). Univariate analysis revealed that LGD (compared to IND) was associated with the primary endpoint, HR 4.02 (1.61-9.71) p<0.01. Of those with multifocal LGD at baseline, univariate analysis showed an association with the primary endpoint, HR 5.08 (0.97-23.79) p=0.05. PSC duration was associated with the endpoint, HR 0.87 (0.74-0.99) p=0.05, in pts with LGD. However, neither was associated with the primary outcome in the multivariate analysis. Among pts with IND, 5-ASA use was associated with a reduced risk of neoplasia progression, HR 0.18 (0.04-0.70) p=0.01 on univariate analysis. A multivariate analysis for the IND group was not performed since 5-ASA use was the only significant association detected. Conclusion: Pts with PSC and UC who developed LGD were more likely to have progressive or persistent neoplasia than those who had IND. However, more than one-quarter of IND pts also developed more advanced lesions. 5-ASA use appeared to protect against neoplasia progression in pts with IND.

Prospective study of the progression of low-grade dysplasia in ulcerative colitis using current cancer surveillance guidelines

The goal of this study was to assess the natural history of low-grade dysplasia (LGD) and its risk of progression in ulcerative colitis (UC) patients by prospective endoscopic surveillance. Forty-two UC patients with LGD were followed prospectively using a uniform approach to surveillance colonoscopy with an average of 43 biopsies per exam. The interval between colonoscopies ranged from 3-12 months. Progression was defined as development of high-grade dysplasia (HGD) or cancer at subsequent colonoscopy or at colectomy. Univariate and multivariate analysis were performed to identify risk factors associated with progression. Patients were followed for an average of 3.9 years (range 1-13). Over that period 19% (8/42) of patients progressed to advanced neoplasia (two cancer, six HGD) while 17% (7/42) had persistent LGD and 64% (27/42) had indefinite dysplasia or no dysplasia at the end of follow-up. Multivariate analysis demonstrated that the number of biopsies with LGD at baseline was associated with an increased risk of progression to advanced neoplasia (relative risk [RR] 5.8, 95% confidence interval [CI]: (1.29-26.04). Among the 15 patients who underwent colectomy, four were found to have higher-grade neoplasia on their colectomy specimen than their preoperative colonoscopy, and these patients were more likely to be nonadherent with recommendations for colectomy. The majority (81%) of UC patients with LGD did not progress to higher grades of dysplasia during a 4-year follow-up. Patients with three or more biopsies demonstrating LGD at a single colonoscopy were at increased risk for progression to advanced neoplasia.

Risk Factors for Progression of Low-Grade Dysplasia in Patients With Barrett's Esophagus

Data vary on the progression of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE); in patients with LGD, we investigated the incidence of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) and compared progression in patients with different forms of LGD (prevalent vs incident and multifocal vs unifocal). We assessed the effects of consensus diagnosis of LGD on progression rates to HGD and EAC among expert pathologists. In a multicenter outcomes project, 210 patients with BE and LGD (classified as incident, prevalent, or persistent) were included. Patients were followed up for an average of 6.2 years (959.6 patient-years). Persistent LGD was defined as detection of LGD on ≥2 consecutive occasions during the follow-up period and extent as either unifocal (LGD at one level of BE segment) or multifocal (>1 level). Histology specimens were reviewed by 2 blinded pathologists. Six patients developed EAC (incidence of 0.44%/year), and 21 developed HGD (incidence of 1.6%/year). The incidence of the combination of HGD and EAC was 1.83%/year. There were no associations between presence of prevalent, incident, or persistent LGD and the extent of LGD with progression rates. Based on consensus diagnosis of 88 reviewed specimens, there was no difference in the progression of LGD to either EAC (the incidence based on analyses by the local pathologist was 0.18%/year, the incidence when there was agreement between the local and one central pathologist was 0.21%/year, and the incidence when all 3 pathologists were in agreement was 0.39%/year) or combined HGD and EAC (0.94%/year, 0.87%/year, and 0.84%/year, respectively). Overall, patients with BE and LGD have a low annual incidence of EAC, similar to nondysplastic BE. There are no risk factors for progression and there is significant interobserver variation in diagnosis, even among expert pathologists.

Sa1547 The Efficacy of Cryospray Ablation Therapy in Eradicating Dysplastic Barrett's Esophagus

The Efficacy of Cryospray Ablation Therapy in Eradicating Dysplastic Barrett’s Esophagus Jayaprakash Sreenarasimhaiah, Deepak Agrawal, Luis F. Lara Medicine/Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX Background: Dysplastic Barrett’s esophagus has historically been treated by surgery. However, endoscopic therapy has recently become well-established as a minimally-invasive alternative. One of the newest modalities available is cryospray ablation therapy. Aims: To determine if cryospray ablation therapy is a safe and effective means for ablation of dysplastic Barrett’s esophagus. Methods: All consecutive patients who underwent cryospray ablation therapy for dysplastic Barrett’s esophagus over a 24-month period were included. Patients were treated with liquid nitrogen (CSA Medical) for high-grade dysplasia (HGD) or persistent low-grade dysplasia (LGD, noted on two endoscopies at 6-month intervals). Nodules were treated with a combination of endoscopic mucosal resection (EMR) and cryospray ablation therapy. Endoscopic ultrasound was used to confirm that disease was confined to the esophageal mucosa in high-grade dysplastic or nodular carcinoma cases. Results: The study group included 26 patients (mean age 67.1 years; 19 male and 7 female) who underwent a total of 57 sessions of cryospray ablation therapy. The mean number of sessions was 2.2 per patient with a mean length of 5.7cm. HGD was seen in 14 patients; intramucosal cancer was noted in 3 patients; persistent LGD was present in 9 patients. Three patients were lost to follow-up due to insurance or co-morbid illness. Of 23 patients who completed therapy, 20 (87%) had no visible Barrett’s mucosa. In 3 /23 (13%), histologic features of Barrett’s mucosa was noted without dysplasia. In all 3 patients with intramucosal nodular carcinoma, endoscopic therapy was successful with no findings at 6 months cryospray alone (1), EMR prior to cryotherapy (1), and EMR following cryotherapy (1). No patients required narcotics or hospitalization following the procedure. In 57 sessions of cryotherapy, 3 (5%) strictures developed which were treated successfully with endoscopic balloon dilation. Conclusions: Cryospray ablation therapy is effective in the complete eradication of Barrett’s with high-grade dysplasia, low-grade dysplasia, and intramucosal (T1) carcinoma. This therapy can be successfully combined with EMR therapy. The low stricture rate and lack of significant post-procedure pain demonstrate the safety and attractiveness of this modality.

Clearance of Human Papillomavirus in Women Treated for Cervical Dysplasia

To estimate human papillomavirus (HPV) clearance of women with cervical abnormalities after treatment. Women attending dysplasia clinics between 2001 and 2007 with a new diagnosis of high-grade dysplasia or persistent low-grade dysplasia requiring treatment by excision or laser ablation were invited to participate. Cervical cytology, histology of biopsies collected at colposcopy, and HPV DNA detection and genotyping of 37 HPV genotypes on specimens collected at treatment and subsequent routine visits were examined. A log-rank test was used to compare the survival distribution between groups. Of the 1,649 women eligible at treatment (baseline), 1,207 (73%) were included in the analysis; 96% (n=1,159) had three or more posttreatment visits. At baseline and the subsequent three follow-up visits, the prevalence of women with HPV DNA detected was 84%, 53% (on average, 6.3 months after baseline), 44% (on average, 15.7 months after baseline), and 45% (on average, 24.3 months after baseline). The median time to HPV clearance was approximately 6 months for either HPV 16 (n=387) or HPV 18 (n=96), irrespective of concurrent detection of other types. On average, HPV 16 or HPV 18 types cleared faster than other types (P<.001). This association remained significant after adjustment for age, preoperative histology, number of preoperative histology results, and treatment type. Clearance times of HPV 16 and HPV 18 infections were similar to each another but shorter than other HPV types. III.

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

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. To assess the safety and efficacy of CRYO in BE with HGD. Multicenter, retrospective cohort study. Nine academic and community centers; treatment period, 2007 to 2009. Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. CRYO with follow-up biopsies. 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. 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%). 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. CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.