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Background: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. Methods: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. Results: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). Conclusions: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required. [ABSTRACT FROM AUTHOR]

Since linked color imaging (LCI) has been reported to increase the color differences in Barrett's esophageal adenocarcinoma (BA) compared to white light imaging (WLI), a comparison of the visibility scores of various imaging techniques for BA is warranted to determine best practice standards. This study is to clarify the role of LCI, blue light imaging (BLI), and WLI in the evaluation of BA. A group of 19 endoscopists, comprised of 6 experts and 13 trainees, evaluated the visibility of WLI, BLI, and LCI images in 21 superficial BA cases. Visibility scores were compared between WLI, BLI, and LCI. Visibility scores were also evaluated for lesion morphology, background Barrett's mucosa, and circumferential location. The visibility scores of experts and trainees were analyzed for comparison. The visibility scores of LCI and BLI were 3.83 and 3.31, respectively, compared to three points for WLI. The visibility of LCI was better than that of WLI regardless of lesion morphology, color, background Barrett's mucosa, and circumferential location. The LCI improved visibility in BA more than the WLI for both experts and trainees. LCI improved the visibility of BA independent of lesion morphology, color, background Barrett's mucosa, circumferential location, and the endoscopist's experience. [ABSTRACT FROM AUTHOR]

Since linked color imaging (LCI) has been reported to increase the color differences in Barrett’s esophageal adenocarcinoma (BA) compared to white light imaging (WLI), a comparison of the visibility scores of various imaging techniques for BA is warranted to determine best practice standards. This study is to clarify the role of LCI, blue light imaging (BLI), and WLI in the evaluation of BA. A group of 19 endoscopists, comprised of 6 experts and 13 trainees, evaluated the visibility of WLI, BLI, and LCI images in 21 superficial BA cases. Visibility scores were compared between WLI, BLI, and LCI. Visibility scores were also evaluated for lesion morphology, background Barrett’s mucosa, and circumferential location. The visibility scores of experts and trainees were analyzed for comparison. The visibility scores of LCI and BLI were 3.83 and 3.31, respectively, compared to three points for WLI. The visibility of LCI was better than that of WLI regardless of lesion morphology, color, background Barrett’s mucosa, and circumferential location. The LCI improved visibility in BA more than the WLI for both experts and trainees. LCI improved the visibility of BA independent of lesion morphology, color, background Barrett’s mucosa, circumferential location, and the endoscopist’s experience.

The diagnosis of Barrett’s esophageal adenocarcinoma (BEA) in patients with Barrett’s esophagus (BE) using endoscopy can be difficult and there are few specific endoscopic findings for BEA. However, white globe appearance (WGA) has been reported to be a specific endoscopic finding for early gastric cancer. We encountered a 51-year-old male patient with BEA exhibiting WGA. Esophagogastroduodenoscopy identified a red, depressed lesion of 10 mm within the long-segment BE (LSBE), while magnifying endoscopy with narrow-band imaging identified WGA. Endoscopic submucosal dissection (ESD) was performed based on our suspicion of BEA. Based on the ESD findings, we diagnosed adenocarcinoma accompanying LSBE histopathologically. WGA was identified, and intraglandular necrotic debris was discovered histologically at the same site. Therefore, WGA may be helpful in the diagnosis of BEA.

Abstract Background The prevalence of Barrett’s esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA. Methods We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2–40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment. Results H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2–40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively. Conclusions Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.

Abstract Background The incidence of metastatic spread of gastrointestinal malignancies to the thyroid gland is relatively low and most of these malignancies originate from the colorectum. Thyroid metastasis originating from the esophagus is poorly documented. Case presentation A 79-year-old man presented with hoarseness of voice and swallowing difficulty. Eighteen months earlier, he had undergone preoperative chemotherapy (S-1 and oxaliplatin [SOX] therapy) and subtotal esophagectomy with regional lymph nodes dissection and retrosternal narrow gastric tube reconstruction for advanced Barrett’s esophageal adenocarcinoma. In the ultrasonographic examination, there was a hypoechoic, indistinct border and heterogeneous nodule in the left lobe of the thyroid gland. Pathological examination of an ultrasound-guided fine-needle aspiration showed adenocarcinoma, supporting a diagnosis of esophageal adenocarcinoma metastases in the thyroid. Conclusion This is a first case of a patient with thyroid metastasis from Barrett’s esophageal adenocarcinoma after subtotal esophagectomy.

The diagnosis of Barrett's esophageal adenocarcinoma (BEA) in patients with Barrett's esophagus (BE) using endoscopy can be difficult and there are few specific endoscopic findings for BEA. However, white globe appearance (WGA) has been reported to be a specific endoscopic finding for early gastric cancer. We encountered a 51-year-old male patient with BEA exhibiting WGA. Esophagogastroduodenoscopy identified a red, depressed lesion of 10 mm within the long-segment BE (LSBE), while magnifying endoscopy with narrow-band imaging identified WGA. Endoscopic submucosal dissection (ESD) was performed based on our suspicion of BEA. Based on the ESD findings, we diagnosed adenocarcinoma accompanying LSBE histopathologically. WGA was identified, and intraglandular necrotic debris was discovered histologically at the same site. Therefore, WGA may be helpful in the diagnosis of BEA. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Barrett's esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA.Methods: We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2-40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment.Results: H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2-40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively.Conclusions: Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens. [ABSTRACT FROM AUTHOR]

Anti-reflux surgery (ARS) for reflux esophagitis is believed to inhibit the progression of Barrett's epithelium (BE), although there is still a chance that Barrett's adenocarcinoma will develop following ARS. Here, we relate our experience of a patient who developed a Barrett's adenocarcinoma despite undergoing ARS. The patient was a 60-year-old male who underwent a Nissen fundoplication 30 years ago due to reflux esophagitis. Endoscopic examination revealed that there was a protruding tumor in the lower thoracic esophagus. The pathological diagnosis of the biopsied specimen was adenocarcinoma. We performed a subtotal esophagectomy with a lymph node dissection and reconstructed the esophagus with an ileocolic interposition. Postoperative pathological diagnosis showed moderately differentiated adenocarcinoma with a BE section. Six lymph nodes were positive for metastasis. The postoperative course was uneventful. Our case suggests that careful surveillance of patients who underwent ARS a long time ago is needed. [ABSTRACT FROM AUTHOR]

It is often difficult to accurately delineate the borders and extent of early-stage esophageal adenocarcinoma in patients with Barrett's esophagus using conventional white light endoscopy. Chromoendoscopy enhances the characteristics of the mucosa and improves detection and delineation of small or flat lesions difficult to identify by conventional endoscopy. Magnifying endoscopy with narrow-band imaging ( NBI) is a novel endoscopic imaging technology that contrasts the vascular architecture and surface structure of the superficial mucosa. As magnifying NBI can view only a narrow area of the mucosa, this method cannot determinethe circumference of the lesion and evaluate its complete extent. Indigocarmine chromoendoscopy is useful for delineating the extent of Barrett's adenocarcinoma. Chromoendoscopy and magnifying NBI are complementary methods, with both being required for the accurate diagnosis of tumor extent in patients with superficial Barrett's esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations ( AVF) by magnifying endoscopy with narrow-band imaging ( ME-NBI), and have verified it by 3- D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontalcross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected. [ABSTRACT FROM AUTHOR]

Abstract Background In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. Results We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed. Conclusion These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma.

The purpose of this review is to highlight the importance of telomeres, the mechanisms implicated in their maintenance, and their role in the etiology as well as the treatment of human esophageal cancer. We will also discuss the role of telomeres in the maintenance and preservation of genomic integrity, the consequences of telomere dysfunction, and the various factors that may affect telomere health in esophageal tissue predisposing it to oncogenesis. There has been growing evidence that telomeres, which can be affected by various intrinsic and extrinsic factors, contribute to genomic instability, oncogenesis, as well as proliferation of cancer cells. Telomeres are the protective DNA-protein complexes at chromosome ends. Telomeric DNA undergoes progressive shortening with age leading to cellular senescence and/or apoptosis. If senescence/apoptosis is prevented as a consequence of specific genomic changes, continued proliferation leads to very short (ie, dysfunctional) telomeres that can potentially cause genomic instability, thus, increasing the risk for activation of telomere maintenance mechanisms and oncogenesis. Like many other cancers, esophageal cancer cells have short telomeres and elevated telomerase, the enzyme that maintains telomeres in most cancer cells. Homologous recombination, which is implicated in the alternate pathway of telomere elongation, is also elevated in Barrett's-associated esophageal adenocarcinoma. Evidence from our laboratory indicates that both telomerase and homologous recombination contribute to telomere maintenance, DNA repair, and the ongoing survival of esophageal cancer cells. This indicates that telomere maintenance mechanisms may potentially be targeted to make esophageal cancer cells static. The rate at which telomeres in healthy cells shorten is determined by a number of intrinsic and extrinsic factors, including those associated with lifestyle. Avoidance of factors that may directly or indirectly injure esophageal tissue including its telomeric and other genomic DNA can not only reduce the risk of development of esophageal cancer but may also have positive impact on overall health and lifespan., (Copyright © 2013 Mosby, Inc. All rights reserved.)