ABSTRACT
BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).
Subject(s)
Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Registries , Humans , Middle Aged , Male , Barrett Esophagus/surgery , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Female , Netherlands/epidemiology , Aged , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Incidence , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Esophagoscopy/adverse effects , Cause of Death , Risk Assessment , Risk Factors , Treatment Outcome , Time Factors , ComorbidityABSTRACT
OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett's oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0-1; 1-2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22-69) and 4 endoscopies (1-5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett's related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039.
Subject(s)
Barrett Esophagus/pathology , Barrett Esophagus/surgery , Esophagoscopy , Radiofrequency Ablation , Aged , Barrett Esophagus/mortality , Cohort Studies , Databases, Factual , Female , Humans , Male , Middle Aged , Netherlands , Recurrence , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Superficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce. OBJECTIVE: Our study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma. METHODS: We retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004-2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low-risk or a high-risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2-mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow-up from histological or PET CT reports when an invasive procedure was not possible. RESULTS: In total, 188 superficial oesophageal adenocarcinomas were included with a median follow-up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high-risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 µm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000-mm threshold for all low-risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%). CONCLUSION: Intramucosal and low-risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow-up. In case of high-risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series.
Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Esophageal Mucosa/pathology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagoscopy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/mortality , Aged , Barrett Esophagus/diagnostic imaging , Barrett Esophagus/mortality , Esophageal Mucosa/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/mortality , Esophagoscopy/adverse effects , Female , Follow-Up Studies , France , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Positron-Emission Tomography , Retrospective Studies , RiskABSTRACT
BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.
Subject(s)
Barrett Esophagus/pathology , Diagnosis, Computer-Assisted/economics , Early Detection of Cancer/economics , Epithelial Cells/pathology , Esophageal Mucosa/pathology , Esophageal Neoplasms/pathology , Gastroesophageal Reflux/pathology , Health Care Costs , Barrett Esophagus/economics , Barrett Esophagus/mortality , Barrett Esophagus/therapy , Biopsy/economics , Computer Simulation , Cost-Benefit Analysis , Decision Support Techniques , Esophageal Neoplasms/economics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Gastroesophageal Reflux/economics , Gastroesophageal Reflux/mortality , Gastroesophageal Reflux/therapy , Humans , Imaging, Three-Dimensional/economics , Male , Middle Aged , Models, Economic , Predictive Value of Tests , Quality-Adjusted Life Years , Risk Factors , Treatment OutcomeABSTRACT
Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status.
Subject(s)
Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Papillomavirus Infections , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Aged , Barrett Esophagus/complications , Barrett Esophagus/diagnosis , Barrett Esophagus/genetics , Barrett Esophagus/mortality , Biomarkers, Tumor/genetics , Case-Control Studies , Disease-Free Survival , Esophageal Neoplasms/complications , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Female , Humans , Ki-67 Antigen/genetics , Male , Middle Aged , Minichromosome Maintenance Complex Component 2/genetics , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Prognosis , Retrospective StudiesSubject(s)
Adenocarcinoma/pathology , Barrett Esophagus/pathology , Early Detection of Cancer/methods , Esophageal Neoplasms/pathology , Esophagoscopy , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Barrett Esophagus/mortality , Barrett Esophagus/therapy , Early Detection of Cancer/standards , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Esophagoscopy/standards , Humans , Neoplasm Staging , Practice Guidelines as Topic , Predictive Value of Tests , Reproducibility of Results , Risk FactorsABSTRACT
BACKGROUND/AIMS: Eradication of early Barrett's neoplasia by endoscopic resection and radiofrequency ablation is safe and effective. In T1b adenocarcinoma, standard of care remains controversial. We investigated the therapeutic outcome between high-grade dysplasia (HGD)/mucosal adenocarcinoma and submucosal adenocarcinoma in Barrett's patients. We hypothesised similar outcome in low-risk (LR) T1b compared to T1a/HGD. METHODS: Patients with endoscopically treated Barrett's esophagus were included in a Swiss tertiary center cohort study. Primary outcome parameter was complete eradication of early neoplasia. Secondary outcome parameters were recurrence-free survival and safety of endoscopic treatment. RESULTS: Forty-eight patients (1 female) with median Barrett's length C4M6 and mean age of 66 years were included. Complete endoscopic eradication of HGD/T1a was achieved in 33 out of 35 and in 11 out of 13 T1b adenocarcinoma. During a median follow-up of 41 (interquartile range 28-63) months no systemic recurrence was observed in endoscopically treated HGD/T1a and LR -T1b and one in a high-risk T1b adenocarcinoma after surgery. Local recurrences were amenable to surgical or endoscopic re-treatment. No lymphnode metastasis was detected in initial staging with esophageal endosonography/positron emission tomography-CT. CONCLUSION: Comparable endoscopic eradication and recurrence rate were observed in HGD/T1a and LR T1b adenocarcinoma. Carefully selected LR T1b cancer may receive endoscopic treatment in an expert center without any negative impact on recurrence.
Subject(s)
Adenocarcinoma/surgery , Barrett Esophagus/surgery , Esophageal Neoplasms/surgery , Esophagoscopy/methods , Neoplasm Recurrence, Local/epidemiology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Catheter Ablation/methods , Disease-Free Survival , Esophageal Mucosa/pathology , Esophageal Mucosa/surgery , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagectomy/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Patient Selection , Retrospective StudiesABSTRACT
BACKGROUND: In recent years, effective outcomes of endoscopic submucosal dissection (ESD) for esophagogastric junction cancer including short-segment Barrett's esophagus (SSBE) cancer have been reported. However, the efficacy of ESD for long-segment Barrett's esophagus (LSBE) cancer is unknown. AIM: To clarify the treatment outcomes of ESD for LSBE cancer versus SSBE cancer. METHODS: A total of 86 patients with 91 superficial Barrett's esophageal adenocarcinomas who underwent ESD were enrolled; of these, 68 had underlying SSBE and 18 had LSBE. Procedure outcomes and prognosis were compared. RESULTS: There was no significant difference in age and tumor diameter among patients. The only complication observed was stricture, but it was not significant (2 vs. 9%). No significant difference was observed in the negative horizontal margin rates (94.1 vs. 95.7%), R0 resection rates (83.8 vs. 82.6%), curative resection rates (72.1 vs. 73.9%), and noncurative factors. Both LSBE and SSBE cancer showed favorable 3-year overall survival rates (95.0 vs. 94.4%) in the median observation period of 28.5 months. CONCLUSIONS: ESD for LSBE cancer achieved procedure outcomes and short-term prognosis comparable to SSBE. ESD has the potential to be an effective therapeutic option for esophageal neoplasms in patients with LSBE.
Subject(s)
Adenocarcinoma/surgery , Barrett Esophagus/pathology , Endoscopic Mucosal Resection/adverse effects , Esophageal Neoplasms/surgery , Esophagoscopy/adverse effects , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Barrett Esophagus/mortality , Barrett Esophagus/surgery , Endoscopic Mucosal Resection/methods , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Stenosis/epidemiology , Esophageal Stenosis/etiology , Esophagoscopy/methods , Esophagus/physiology , Esophagus/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Importance: High-risk human papillomavirus (HPV) has been associated with Barrett dysplasia and esophageal adenocarcinoma. Nevertheless, the prognostic significance of esophageal tumor HPV status is unknown. Objective: To determine the association between HPV infection and related biomarkers in high-grade dysplasia or esophageal adenocarcinoma and survival. Design, Setting, and Participants: Retrospective case-control study. The hypothesis was that HPV-associated esophageal tumors would show a favorable prognosis (as in viral-positive head and neck cancers). Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction, in situ hybridization for E6 and E7 messenger RNA (mRNA), and immunohistochemistry for the proteins p16INK4A and p53. Sequencing of TP53 was also undertaken. The study took place at secondary and tertiary referral centers, with 151 patients assessed for eligibility and 9 excluded. The study period was from December 1, 2002, to November 28, 2017. Main Outcomes and Measures: Disease-free survival (DFS) and overall survival (OS). Results: Among 142 patients with high-grade dysplasia or esophageal adenocarcinoma (126 [88.7%] male; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. Patients who were HPV positive mostly had high p16INK4A expression, low p53 expression, and wild-type TP53. There were more Tis, T1, and T2 tumors in HPV-positive patients compared with HPV-negative patients (75.7% vs 54.3%; difference, 21.4%; 95% CI, 4.6%-38.2%; P = .02). Mean DFS was superior in the HPV-positive group (40.3 vs 24.1 months; difference, 16.2 months; 95% CI, 5.7-26.8; P = .003) as was OS (43.7 vs 29.8 months; difference, 13.9 months; 95% CI, 3.6-24.3; P = .009). Recurrence or progression was reduced in the HPV-positive cohort (24.3% vs 58.1%; difference, -33.8%; 95% CI, -50.5% to -17.0%; P < .001) as was distant metastasis (8.1% vs 27.6%; difference, -19.5%; 95% CI, -31.8% to -7.2%; P = .02) and death from esophageal adenocarcinoma (13.5% vs 36.2%; difference, -22.7%; 95% CI, -37.0% to -8.3%; P = .01). Positive results for HPV and transcriptionally active virus were both associated with a superior DFS (hazard ratio [HR], 0.33; 95% CI, 0.16-0.67; P = .002 and HR, 0.44; 95% CI, 0.22-0.88; P = .02, respectively [log-rank test]). Positivity for E6 and E7 mRNA, high p16INK4A expression, and low p53 expression were not associated with improved DFS. On multivariate analysis, superior DFS was demonstrated for HPV (HR, 0.39; 95% CI, 0.18-0.85; P = .02), biologically active virus (HR, 0.36; 95% CI, 0.15-0.86; P = .02), E6 and E7 mRNA (HR, 0.36; 95% CI, 0.14-0.96; P = .04), and high p16 expression (HR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: Barrett high-grade dysplasia and esophageal adenocarcinoma in patients who are positive for HPV are distinct biological entities with a favorable prognosis compared with viral-negative esophageal tumors. Confirmation of these findings in larger cohorts with more advanced disease could present an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival.
Subject(s)
Adenocarcinoma/complications , Adenocarcinoma/mortality , Barrett Esophagus/complications , Barrett Esophagus/mortality , Esophageal Neoplasms/complications , Esophageal Neoplasms/mortality , Papillomavirus Infections/complications , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival RateABSTRACT
BACKGROUND & AIMS: A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. METHODS: We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow-up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median, 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios and 95% confidence intervals to determine associations between risk of progression and scores. RESULTS: Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4 ± 20.1 years; mean body mass index, 27.9 ± 5.5 kg/m2; mean length of BE, 3.7 ± 3.2 cm). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% confidence interval, 0.72-0.80; P < .001). The calibration slope was 0.9966 (P = .99), determined from the validation cohort. CONCLUSIONS: We developed a scoring system (Progression in Barrett's Esophagus score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia that identified patients with BE at low, intermediate, and high risk for HGD or EAC. This scoring system might be used in management of patients.
Subject(s)
Adenocarcinoma/epidemiology , Barrett Esophagus/epidemiology , Decision Support Techniques , Esophageal Neoplasms/epidemiology , Esophagus/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adult , Aged , Barrett Esophagus/diagnosis , Barrett Esophagus/mortality , Biopsy , Cigarette Smoking/adverse effects , Databases, Factual , Disease Progression , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophagoscopy , Female , Humans , Incidence , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Neoplasm Grading , Netherlands/epidemiology , Predictive Value of Tests , Proportional Hazards Models , Reproducibility of Results , Risk Assessment , Risk Factors , Sex Factors , Time Factors , United States/epidemiologySubject(s)
Adenocarcinoma/epidemiology , Barrett Esophagus/epidemiology , Esophageal Neoplasms/epidemiology , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Barrett Esophagus/diagnosis , Barrett Esophagus/mortality , Barrett Esophagus/therapy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Humans , Prognosis , Risk Factors , SEER Program , United States/epidemiologyABSTRACT
AIM: To elucidate longitudinal changes of an endoscopic Barrett esophagus (BE), especially of short segment endoscopic BE (SSBE). METHODS: This study comprised 779 patients who underwent two or more endoscopies between January 2009 and December 2015. The intervals between the first and the last endoscopy were at least 6 mo. The diagnosis of endoscopic BE was based on the criteria proposed by the Japan Esophageal Society and was classified as long segment (LSBE) and SSBE, the latter being further divided into partial and circumferential types. The potential background factors that were deemed to affect BE change included age, gender, antacid therapy use, gastroesophageal reflux disease-suggested symptoms, esophagitis, and hiatus hernia. Time trends of a new appearance and complete regression were investigated by Kaplan-Meier curves. The factors that may affect appearance and complete regression were investigated by χ(2) and Student-t tests, and multivariable Cox regression analysis. RESULTS: Incidences of SSBE and LSBE were respectively 21.7% and 0%, with a mean age of 68 years. Complete regression of SSBE was observed in 61.5% of initial SSBE patients, while 12.1% of initially disease free patients experienced an appearance of SSBE. Complete regressions and appearances of BE occurred constantly over time, accounting for 80% and 17% of 5-year cumulative rates. No LSBE development from SSBE was observed. A hiatus hernia was the only significant factor that facilitated BE development (P = 0.03) or hampered (P = 0.007) BE regression. CONCLUSION: Both appearances and complete regressions of SSBE occurred over time. A hiatus hernia was the only significant factor affecting the BE story.
Subject(s)
Barrett Esophagus/complications , Barrett Esophagus/epidemiology , Endoscopy/methods , Esophagitis/complications , Adult , Barrett Esophagus/mortality , Cohort Studies , Esophagus/pathology , Female , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/mortality , Hernia, Hiatal/complications , Humans , Incidence , Japan , Longitudinal Studies , Male , Metaplasia , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Regression AnalysisABSTRACT
Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barrett's esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.
Subject(s)
Adenocarcinoma/chemistry , Barrett Esophagus/metabolism , Carcinoma, Squamous Cell/chemistry , Cell Proliferation , Cyclin E/analysis , Esophageal Neoplasms/chemistry , Ki-67 Antigen/analysis , Minichromosome Maintenance Complex Component 4/analysis , Minichromosome Maintenance Complex Component 7/analysis , Polycomb Repressive Complex 1/analysis , Precancerous Conditions/chemistry , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chi-Square Distribution , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Multivariate Analysis , Neoplasm Grading , Precancerous Conditions/mortality , Precancerous Conditions/pathology , Predictive Value of Tests , Reproducibility of Results , Risk Factors , Tissue Array AnalysisABSTRACT
INTRODUCTION: Barrett's esophagus is a metaplastic change in the lower esophagus that results from long-standing gastro-esophageal reflux disease, associated with a risk of development of esophageal adenocarcinoma. This review examines the role of antireflux surgery in the management of Barrett's esophagus. EVIDENCE ACQUISITION: A systematic review of the EMBASE and MEDLINE databases (1974-2016) was undertaken to identify studies with long-term follow-up examining the role of antireflux surgery in Barrett's esophagus. Outcomes examined were: number of subjects, follow-up, rates of progression, regression and adenocarcinoma. Symptomatic outcomes, surgical morbidity and rates of surgical failure were included when available. EVIDENCE SYNTHESIS: A total of 2403 articles were identified of which 9 met the inclusion criteria for this study using the PRISMA methodology. Citation tracking identified 3 further studies for inclusion. There were 962 patients included in this study, 731 who were found to have completed endoscopic follow up with a total of 3736 years of follow up. Annual incidence of esophageal adenocarcinoma was found to be 0.18%. Thirty-five percent of patients (260 patients) had regression. Progression was seen in 8% (57 patients) postoperatively. There was no mortality. CONCLUSIONS: There is insufficient evidence to recommend surgery over medical therapy to reduce cancer risk in Barrett's esophagus. Regression of features associated with cancer risk was more common after surgery than medical therapy. Surgery has been shown to improve patients' gastroesophageal reflux disease-specific quality of life. Long-term, antireflux surgery represents a cost effective method to manage Barrett's Esophagus with continued endoscopic surveillance.
Subject(s)
Barrett Esophagus/surgery , Esophagoscopy , Fundoplication , Adenocarcinoma/etiology , Barrett Esophagus/complications , Barrett Esophagus/diagnosis , Barrett Esophagus/mortality , Disease Progression , Esophageal Neoplasms/etiology , Esophagoscopy/methods , Evidence-Based Medicine , Fundoplication/methods , Humans , Prognosis , Quality of Life , Randomized Controlled Trials as Topic , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Several studies have evaluated the prognostic value of HER2 in oesophageal cancer, but the prognostic influence of HER2 overexpression in oesophageal cancer remains uncertain. The aim of this study was to assess the incidence of HER2 positivity and relationship with clinicopathological features in patients with oesophageal cancer. DESIGN: The study cohort consisted of 269 patients diagnosed with oesophageal carcinoma in a single institution. HER2 expression was analysed by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival analysis was assessed using Hazard models. RESULTS: HER2 expression was IHC3+ in 14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases. SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among 27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of 125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95% CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71-20.00). There was no significant difference in survival between the (HER2 +ve, 14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence rate of 9.9% was found among patients with oesophageal cancer and no correlation with survival was detected overall.
Subject(s)
Barrett Esophagus/genetics , Barrett Esophagus/mortality , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Receptor, ErbB-2/genetics , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Australia , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Cohort Studies , Disease-Free Survival , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagectomy/mortality , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS: We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS: Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS: Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.
Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/prevention & control , Barrett Esophagus/mortality , Barrett Esophagus/surgery , Catheter Ablation/mortality , Esophageal Neoplasms/mortality , Esophageal Neoplasms/prevention & control , Adenocarcinoma/diagnosis , Aged , Aged, 80 and over , Barrett Esophagus/diagnosis , Catheter Ablation/adverse effects , Cause of Death , Chi-Square Distribution , Esophageal Neoplasms/diagnosis , Female , Humans , Incidence , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Protective Factors , Registries , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States/epidemiologyABSTRACT
In the last 5-10 years, endoscopic ablative therapies have been gaining ground as treatment for Barrett's esophagus associated with high-grade dysplasia and early cancer, and they are becoming the most preferred technique over surgery as the standard of care. These therapies are associated with a lower rate of complications and mortality than surgery; studies have found them to be safe, effective and tolerable. Endoscopic ablative therapies are not, however, without their drawbacks. There is a paucity of data on long-term efficacy, and direct comparisons of the different modalities are lacking. Unlike surgery, current data suggest that endoscopic ablation treatments may not be curative in all patients, so patients require ongoing surveillance and acid suppression. Questions remain regarding durability as well as factors promoting recurrence after endoscopic therapy. The authors conducted a systematic review of the literature on ablative therapies in Barrett's esophagus to describe the modalities currently available and to provide an understanding of their limitations.
Subject(s)
Ablation Techniques/adverse effects , Barrett Esophagus/surgery , Esophagoscopy/adverse effects , Postoperative Complications/etiology , Ablation Techniques/mortality , Barrett Esophagus/diagnosis , Barrett Esophagus/mortality , Esophagoscopy/mortality , Humans , Postoperative Complications/mortality , Postoperative Complications/therapy , Recurrence , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal cancer. Though surgery can completely resect the cancer and the affected lymph nodes, it carries significant morbidity and mortality (often exceeds 2%). New developments in endoscopy have provided less-invasive therapies that can also be used to stage tissue invasion of cancer; they include esophageal mucosal resection (EMR) and endoscopic submucosal dissection. Additional endoscopic therapies include photodynamic therapy, radiofrequency ablation (RFA) and argon plasma coagulation. Combining EMR that targets the cancer and RFA that targets the surrounding Barrett's esophagus offers an alternative to the operative approach when there is no lymph node metastasis. Arguments for surgical esophagectomy include concern for missed lymph node metastasis and incomplete endoscopic resection. Based on EMR's high neoplasia eradication rate and its fewer and more manageable complications, EMR, especially when combined with RFA, appears to be a viable alternative to surgery in early submucosal cancers, that is, sm1.
Subject(s)
Ablation Techniques , Adenocarcinoma/surgery , Barrett Esophagus/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagoscopy/methods , Ablation Techniques/adverse effects , Ablation Techniques/mortality , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Barrett Esophagus/diagnosis , Barrett Esophagus/mortality , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophagectomy/adverse effects , Esophagectomy/mortality , Esophagoscopy/adverse effects , Esophagoscopy/mortality , Humans , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.