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Mo1862 Targeted Biopsies Are Not Accurate Enough for Correct Diagnosis of Early Esophageal Neoplasia
in the progression to cancer when measured with multiple markers. P16 is a strong marker for clonal populations in BE and dysplasia and the finding that SC are able to induce proliferation in non-senescent cells suggests a mechanism to explain how interactions between clonal populations may promote expansion of tumorigenic clones.
Mo1861
Mo1860
Background and aims: The value of surveillance for Barrett's esophagus (BE) is under discussion given the overall low incidence of neoplastic progression, the large screening base, and the lack of discriminative tests for risk stratification. One of the key questions in this discussion is whether BE surveillance reduces mortality due to esophageal adenocarcinoma (EAC). The aim of this study was therefore to evaluate the survival of BE patients diagnosed with high-grade dysplasia (HGD) or EAC in a surveillance program. Methods: We conducted a large multicenter prospective cohort study in 3 academic and 12 regional hospitals throughout the Netherlands. Between November 2003 and December 2004 all patients were included presenting at the endoscopy unit with BE of at least 2 cm. The endoscopic diagnosis was confirmed by the presence of intestinal metaplasia. Surveillance was performed according to the ACG guidelines and biopsies were taken according to the Seattle protocol. Biopsies were graded by a local pathologist and at least one expert pathologist for second opinion. Pathologists were blinded to the diagnosis of each other and a final diagnosis was made only if at least 2 pathologists agreed on the grade of dysplasia. Incident cases of HGD and EAC were identified during follow-up. Results: 720 BE patients (73% male, median age 61 years (IQR 53-69)) were included in the study and surveyed for a median duration of 6.6 years (IQR 5.1-7.3). Fifty (7%) patients showed neoplastic progression after a median follow-up of 3.2 years (IQR 2.0-5.3). Thirty-nine (78%) patients were diagnosed with HGD or carcinoma in situ, 7 (14%) with a T1 tumor, 2 (4%) with a T2 tumor and 2 (4%) with a T3 tumor. The incidence rate of HGD and EAC was 1.3 per 100 patientyears (95% CI 0.9-1.7) and the incidence rate of invasive EAC was 0.1 per 100 patientyears (95% CI 0.0-0.3). The incidence rate of neoplastic progression and tumor stage did not significantly change over time. After the diagnosis, 9 (18%) patients received endoscopic surveillance, 30 (60%) received endoscopic treatment, 4 (8%) received surgical resection, and 2 (4%) received surgical resection with neoadjuvant chemoradiotherapy. Four (8%) patients were only recently diagnosed and did not yet receive treatment. One (2%) patient died before treatment of a cause not related to BE. The 5-year HGD/EAC specific survival was 91% (95% CI 0.81-1.00) and the 5-year overall survival was 78% (95% CI 0.61-0.94). Conclusion: BE surveillance enables the detection of HGD or EAC at an early and curable stage when endoscopic treatment is still feasible. The 5-year disease specific survival of all HGD/EAC patients was 91%, which is the most optimal survival rate that can be achieved in esophageal cancer patients according to AJCC TNM system definitions (stage 0 disease, TisN0M0, 5-year survival .90%).
Influence of Histological Variables on Long-Term Outcomes in Barrett's Esophagus Related T1 Esophageal Adenocarcinoma Prasad G. Iyer, Jason T. Lewis, Tsung-Teh Wu, Cathy D. Schleck, Alan R. Zinsmeister, Kelly T. Dunagan, Lori S. Lutzke, Kenneth K. Wang Background: The endoscopic management of mucosal (T1a) esophageal adenocarcinoma (EAC) has gained acceptance given supportive data on outcomes, in comparison to esophagectomy from multiple centers. There is limited data on predictors of outcomes, particularly baseline histological variables such as grade of differentiation, presence of lympho-vascular invasion (LVI) and depth of invasion (lamina propria [LP], muscularis mucosa [MM], superficial submucosa [SM]). We aimed to assess the influence of these histological variables on overall and cancer free survival in a large a large tertiary care center. Methods: All cases of T1 EAC treated endoscopically using endoscopic mucosal resection (EMR) between 1995 to 2011 were identified using a prospectively maintained endoscopic database. Patients underwent staging with endoscopic ultrasound (EUS), CT Scan and PET scans. EMR histology was sytematically reviewed by two gastrointestinal pathologists to assess: grade of differentiation, precise depth of invasion (LP, MM, SM), lymphovascular invasion (LVI) and status of deep and lateral margins (positive or negative for carcinoma). Clinical, demographic and endoscopic data was abstracted from the prospective database. Vital status data was obtained using an institutionally approved internet based service (www.accurint.com). Overall and cancer free survival were estimated using the Kaplan-Meier method, and predictors of survival were assessed using Cox proportional hazards models. Results: A total of 205 cases with T1 EAC were identified among which 148 (72.2%) had T1a (mucosal) EAC while 57 (27.8%) had T1b (SM) EAC. Baseline clinical and histological characteristics are summarized in table 1. A majority of T1a cancers were well or moderately differentiated (83%) with invasion of the muscularis mucosa in 80%. LVI was present in a small (11%, 16/148) proportion of T1a patients, with deep margins being positive in 21% (31/148) patients. T1b EAC had lower (65%) proportion of well/moderately differentiation, and higher proportions of LVI (40%) and deep margin positivity (72%). The cumulative probability of remission by 5 years in this subset was 89.7%. Among the T1a EAC subjects, 33 (22.3%) underwent esophagectomy. Overall, 9 (6 in T1a group and 3 in T1b group) had recurrence of carcinoma and 14 (9 in T1a group and 5 in T1b group) had recurrence of dysplasia. Overall survival and cancer free survival in the T1a EAC subset was 73.4 % and 94.5% at 5 years. Predictors of overall survival are shown in table 2. Conclusions: T1a cancers have lower rates of poor differentiation, LVI and deep margin positivity than T1b cancers. These histological variables do not appear to predict long term outcomes (overall and cancer free survival). Increasing age predicts mortality in patients with T1a cancers treated endoscopically.
Mo1862 Targeted Biopsies Are Not Accurate Enough for Correct Diagnosis of Early Esophageal Neoplasia Magdalena Stefanova, Inna Tuckova, Alice Strosova, Julius Spicak, Jan Martinek INTRODUCTION: Endoscopic resection (ER) is a method of treatment of early esophageal neoplasia if a visible lesion is present. Radiofrequency ablation (RFA) is indicated for patients with high grade intraepithelial neoplasia (HGIN) without visible lesions. However, it is not clear, whether the targeted biopsies are sufficient for definitive diagnosis of early esophageal neoplasia, especially in the patients without a visible lesion. AIM: To compare diagnostic yield of targeted biopsies compared with ER in patients with early esophageal neoplasia. The main outcome measurement was a revision/review of histopathological stage. METHODS: A total of 59 patients (7 women, 52 men, mean age 63 years, range 34-85) undergoing both targeted esophageal biopsies and ER (n=53) or ESD (n=1) were analyzed. Index diagnosis according to the biopsy specimen was as follows: 14x early carcinoma (EC) (13x adenocarcinoma, 1x squamous carcinoma), 26x HGIN (25x adenomatous, 1x sqamous), 15x low grade intraepithelial neoplasia (LGIN, all adenomatous), 3x hyperplastic lesion and 1x papilloma. The lesions were classified according to the Paris classification: 0-Is 4x, 0-IIa 28x, 0-IIb 24x, 0-IIa+IIc 3x. In most of the cases, ER with multiband ligation device was used. All histopathological specimens were analyzed by an experienced pathologist. RESULTS: Compared to prior forceps biopsy, histopathology from ER specimen changed in 24 patients (40%). All carcinomas diagnosed from biopsies were confirmed in ER specimens. Among 26 patients with HGIN, the diagnosis was confirmed in 8 patients. In 10 patients, the final diagnosis has been up-staged from HGIN to cancer (4 patients had a flat lesion IIb). In 8 patients, the final diagnosis has been down-staged from HGIN to LGIN or to no intraepithelial neoplasia. Among 15 patients with LGIN, the diagnosis was confirmed in 10 patients, upstaged from LGIN to HGIN in 1 patient and to cancer in 2 patients, down-staged from LGIN to no intraepithelial neoplasia in 2 patients. The sensitivity of biopsies for cancer diagnosing was 0.54 (95%CI 0.3-0.72) and the specificity was 1.0 (95%CI 0.9-1). CONCLUSION: Targeted biopsies are not accurate enough for precise diagnosis of early esophageal neoplasia. There is a clinically significant change in histopathological diagnosis after ER. RFA treatment should be indicated cautiosly in patients without a visible lesion and with HGIN diagnosed using standard biopsies. Mo1863 Correlation of qRT-PCR With State of the Art Next Generation Sequencing for High-Throughput MicroRNA Analysis in Barrett's Esophagus: Implications for Interpretation of Sequencing Results In-hee Lee, Xiaoman Hong, Amit Rastogi, Sharad C. Mathur, Prateek Sharma, Lane K. Christenson, Ajay Bansal Background Next generation sequencing (NGS) is a novel, unbiased, state of the art technology for the study of known as well as the unknown microRNA (miRNA). However, the correlation of reads by NGS with qRT-PCR remains incompletely understood and has an impact on interpretation of the NGS results. Aim To understand the relation between reads identified by NGS and their measurement by qRT-PCR in patients with Barrett's esophagus
S-677
AGA Abstracts
AGA Abstracts
Survival of Patients With Barrett-Related Adenocarcinoma Detected in a Surveillance Program: Results of a Large Multicenter Prospective Cohort Study Florine Kastelein, Manon C. Spaander, Sophie van Olphen, Katharina Biermann, Leendert Looijenga, Ewout W. Steyerberg, Ernst J. Kuipers, Marco J. Bruno
Mo1861
Mo1860
Background and aims: The value of surveillance for Barrett's esophagus (BE) is under discussion given the overall low incidence of neoplastic progression, the large screening base, and the lack of discriminative tests for risk stratification. One of the key questions in this discussion is whether BE surveillance reduces mortality due to esophageal adenocarcinoma (EAC). The aim of this study was therefore to evaluate the survival of BE patients diagnosed with high-grade dysplasia (HGD) or EAC in a surveillance program. Methods: We conducted a large multicenter prospective cohort study in 3 academic and 12 regional hospitals throughout the Netherlands. Between November 2003 and December 2004 all patients were included presenting at the endoscopy unit with BE of at least 2 cm. The endoscopic diagnosis was confirmed by the presence of intestinal metaplasia. Surveillance was performed according to the ACG guidelines and biopsies were taken according to the Seattle protocol. Biopsies were graded by a local pathologist and at least one expert pathologist for second opinion. Pathologists were blinded to the diagnosis of each other and a final diagnosis was made only if at least 2 pathologists agreed on the grade of dysplasia. Incident cases of HGD and EAC were identified during follow-up. Results: 720 BE patients (73% male, median age 61 years (IQR 53-69)) were included in the study and surveyed for a median duration of 6.6 years (IQR 5.1-7.3). Fifty (7%) patients showed neoplastic progression after a median follow-up of 3.2 years (IQR 2.0-5.3). Thirty-nine (78%) patients were diagnosed with HGD or carcinoma in situ, 7 (14%) with a T1 tumor, 2 (4%) with a T2 tumor and 2 (4%) with a T3 tumor. The incidence rate of HGD and EAC was 1.3 per 100 patientyears (95% CI 0.9-1.7) and the incidence rate of invasive EAC was 0.1 per 100 patientyears (95% CI 0.0-0.3). The incidence rate of neoplastic progression and tumor stage did not significantly change over time. After the diagnosis, 9 (18%) patients received endoscopic surveillance, 30 (60%) received endoscopic treatment, 4 (8%) received surgical resection, and 2 (4%) received surgical resection with neoadjuvant chemoradiotherapy. Four (8%) patients were only recently diagnosed and did not yet receive treatment. One (2%) patient died before treatment of a cause not related to BE. The 5-year HGD/EAC specific survival was 91% (95% CI 0.81-1.00) and the 5-year overall survival was 78% (95% CI 0.61-0.94). Conclusion: BE surveillance enables the detection of HGD or EAC at an early and curable stage when endoscopic treatment is still feasible. The 5-year disease specific survival of all HGD/EAC patients was 91%, which is the most optimal survival rate that can be achieved in esophageal cancer patients according to AJCC TNM system definitions (stage 0 disease, TisN0M0, 5-year survival .90%).
Influence of Histological Variables on Long-Term Outcomes in Barrett's Esophagus Related T1 Esophageal Adenocarcinoma Prasad G. Iyer, Jason T. Lewis, Tsung-Teh Wu, Cathy D. Schleck, Alan R. Zinsmeister, Kelly T. Dunagan, Lori S. Lutzke, Kenneth K. Wang Background: The endoscopic management of mucosal (T1a) esophageal adenocarcinoma (EAC) has gained acceptance given supportive data on outcomes, in comparison to esophagectomy from multiple centers. There is limited data on predictors of outcomes, particularly baseline histological variables such as grade of differentiation, presence of lympho-vascular invasion (LVI) and depth of invasion (lamina propria [LP], muscularis mucosa [MM], superficial submucosa [SM]). We aimed to assess the influence of these histological variables on overall and cancer free survival in a large a large tertiary care center. Methods: All cases of T1 EAC treated endoscopically using endoscopic mucosal resection (EMR) between 1995 to 2011 were identified using a prospectively maintained endoscopic database. Patients underwent staging with endoscopic ultrasound (EUS), CT Scan and PET scans. EMR histology was sytematically reviewed by two gastrointestinal pathologists to assess: grade of differentiation, precise depth of invasion (LP, MM, SM), lymphovascular invasion (LVI) and status of deep and lateral margins (positive or negative for carcinoma). Clinical, demographic and endoscopic data was abstracted from the prospective database. Vital status data was obtained using an institutionally approved internet based service (www.accurint.com). Overall and cancer free survival were estimated using the Kaplan-Meier method, and predictors of survival were assessed using Cox proportional hazards models. Results: A total of 205 cases with T1 EAC were identified among which 148 (72.2%) had T1a (mucosal) EAC while 57 (27.8%) had T1b (SM) EAC. Baseline clinical and histological characteristics are summarized in table 1. A majority of T1a cancers were well or moderately differentiated (83%) with invasion of the muscularis mucosa in 80%. LVI was present in a small (11%, 16/148) proportion of T1a patients, with deep margins being positive in 21% (31/148) patients. T1b EAC had lower (65%) proportion of well/moderately differentiation, and higher proportions of LVI (40%) and deep margin positivity (72%). The cumulative probability of remission by 5 years in this subset was 89.7%. Among the T1a EAC subjects, 33 (22.3%) underwent esophagectomy. Overall, 9 (6 in T1a group and 3 in T1b group) had recurrence of carcinoma and 14 (9 in T1a group and 5 in T1b group) had recurrence of dysplasia. Overall survival and cancer free survival in the T1a EAC subset was 73.4 % and 94.5% at 5 years. Predictors of overall survival are shown in table 2. Conclusions: T1a cancers have lower rates of poor differentiation, LVI and deep margin positivity than T1b cancers. These histological variables do not appear to predict long term outcomes (overall and cancer free survival). Increasing age predicts mortality in patients with T1a cancers treated endoscopically.
Mo1862 Targeted Biopsies Are Not Accurate Enough for Correct Diagnosis of Early Esophageal Neoplasia Magdalena Stefanova, Inna Tuckova, Alice Strosova, Julius Spicak, Jan Martinek INTRODUCTION: Endoscopic resection (ER) is a method of treatment of early esophageal neoplasia if a visible lesion is present. Radiofrequency ablation (RFA) is indicated for patients with high grade intraepithelial neoplasia (HGIN) without visible lesions. However, it is not clear, whether the targeted biopsies are sufficient for definitive diagnosis of early esophageal neoplasia, especially in the patients without a visible lesion. AIM: To compare diagnostic yield of targeted biopsies compared with ER in patients with early esophageal neoplasia. The main outcome measurement was a revision/review of histopathological stage. METHODS: A total of 59 patients (7 women, 52 men, mean age 63 years, range 34-85) undergoing both targeted esophageal biopsies and ER (n=53) or ESD (n=1) were analyzed. Index diagnosis according to the biopsy specimen was as follows: 14x early carcinoma (EC) (13x adenocarcinoma, 1x squamous carcinoma), 26x HGIN (25x adenomatous, 1x sqamous), 15x low grade intraepithelial neoplasia (LGIN, all adenomatous), 3x hyperplastic lesion and 1x papilloma. The lesions were classified according to the Paris classification: 0-Is 4x, 0-IIa 28x, 0-IIb 24x, 0-IIa+IIc 3x. In most of the cases, ER with multiband ligation device was used. All histopathological specimens were analyzed by an experienced pathologist. RESULTS: Compared to prior forceps biopsy, histopathology from ER specimen changed in 24 patients (40%). All carcinomas diagnosed from biopsies were confirmed in ER specimens. Among 26 patients with HGIN, the diagnosis was confirmed in 8 patients. In 10 patients, the final diagnosis has been up-staged from HGIN to cancer (4 patients had a flat lesion IIb). In 8 patients, the final diagnosis has been down-staged from HGIN to LGIN or to no intraepithelial neoplasia. Among 15 patients with LGIN, the diagnosis was confirmed in 10 patients, upstaged from LGIN to HGIN in 1 patient and to cancer in 2 patients, down-staged from LGIN to no intraepithelial neoplasia in 2 patients. The sensitivity of biopsies for cancer diagnosing was 0.54 (95%CI 0.3-0.72) and the specificity was 1.0 (95%CI 0.9-1). CONCLUSION: Targeted biopsies are not accurate enough for precise diagnosis of early esophageal neoplasia. There is a clinically significant change in histopathological diagnosis after ER. RFA treatment should be indicated cautiosly in patients without a visible lesion and with HGIN diagnosed using standard biopsies. Mo1863 Correlation of qRT-PCR With State of the Art Next Generation Sequencing for High-Throughput MicroRNA Analysis in Barrett's Esophagus: Implications for Interpretation of Sequencing Results In-hee Lee, Xiaoman Hong, Amit Rastogi, Sharad C. Mathur, Prateek Sharma, Lane K. Christenson, Ajay Bansal Background Next generation sequencing (NGS) is a novel, unbiased, state of the art technology for the study of known as well as the unknown microRNA (miRNA). However, the correlation of reads by NGS with qRT-PCR remains incompletely understood and has an impact on interpretation of the NGS results. Aim To understand the relation between reads identified by NGS and their measurement by qRT-PCR in patients with Barrett's esophagus
S-677
AGA Abstracts
AGA Abstracts
Survival of Patients With Barrett-Related Adenocarcinoma Detected in a Surveillance Program: Results of a Large Multicenter Prospective Cohort Study Florine Kastelein, Manon C. Spaander, Sophie van Olphen, Katharina Biermann, Leendert Looijenga, Ewout W. Steyerberg, Ernst J. Kuipers, Marco J. Bruno