Optical Biopsy for Esophageal Squamous Cell Neoplasia by Using Endocytoscopy

Background Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. Methods This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We analyzed the diagnostic accuracy of ECS for esophageal tumorous lesions. Results ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity (95% confidence interval (CI)) was 97.6% (87.7%-99.7%), specificity was 100% (92.7%-100%), diagnostic accuracy was 98.9% (94.0%-99.8%), positive predictive value (PPV) was 100% (91.4%-100%) and negative predictive value (NPV) was 98.0% (89.5%-99.7%). Conclusions ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions is considered to be sufficient in clinical practice.

Clinical Case of Treatment of Stage IV Esophageal Cancer

In 2018 in Russian Federation more than 500 thousand new cases of cancer were found, including 8000 cases with malignant tumors of esophagus and more than 30 % of patients have the IV stage. Esophageal cancer takes the 6-th place in death causes connected to cancer in the world and it is still one of the main global problems in medical care. Oncologists face the problem of the most difficult choice in treatment tactics for spread stages of disease. In this situation it is recommended to provide combined treatment (surgery, neoadjuvant and adjuvant chemotherapy). Definitive radiotherapy or chemoradiotherapy (without surgery) is used for patients with unrespectable esophageal tumor. In this article we present clinical case of successful treatment of a patient with metastatic esophageal cancer. The patient got chemoradiotherapy in 2017 and after control checkup in November 2019 remission was registered. After provided treatment stopping of pain syndrome and dysphagia, food passage through esophagus was restored. The patient notes good life quality, he is physically active and socially adapted.

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

Background Plasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA). Methods Specific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98). Results In total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5–87.9%) and a specificity of 94.1% (85.7–98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0–83.6%) and a specificity of 95.9% (89.9–98.9%). Sensitivity for stage 0–II was 58.8% (44.2–72.4%). Conclusion We demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.

Semi-Prone Thoracoscopic Esophagectomy for Esophageal Carcinoma with Aberrant Right Subclavian Artery and Non-Recurrent Inferior Laryngeal Nerve: A Case Report

Background Aberrant right subclavian artery (ARSA) accompanied by non-recurrent inferior laryngeal nerve (NRILN) is a rare anomaly. In cases of thoracic esophageal carcinoma associated with ARSA and NRILN, surgeons must take extra care not to injury these vessels and nerves. We believe semi-prone thoracoscopic esophagectomy to be a surgical approach that can safely deal with such an anomaly. Case presentation: A 70-year-old man complained of feelings of chest constriction. Endoscopic examination revealed an esophageal tumor and computed tomography showed an ARSA. we performed semi-prone thoracoscopic esophagectomy for case with ARSA and NRILN. We identified these anomalies during esophagectomy, and we could complete surgery without injury these vessels and nerves. The patient had an uneventful recovery and discharged 22 days after surgery. Conclusions Semi-prone thoracoscopic esophagectomy for esophageal carcinoma can be performed safely with a wide operative field, and is an excellent procedure for dissecting esophageal carcinoma in patients with ARSA and NRILN.

EGFR-IL-6 Signaling Axis Mediated the Inhibitory Effect of Methylseleninic Acid on Esophageal Squamous Cell Carcinoma

Epidemiological and experimental evidence indicate that selenium is associated with a reduced risk of some cancers, including esophageal cancer. However, the exact mechanism is still unclear. In the present study, we used esophageal squamous cell carcinoma (ESCC) cell lines and animal models to explore the anti-cancer mechanism of methylseleninic acid (MSA). Firstly, MSA treatment dramatically attenuated Epidermal Growth Factor Receptor (EGFR) protein expression but did not alter mRNA levels in ESCC cells. On the contrary, EGFR overexpression partly abolished the inhibitory effect of MSA. With a microRNA-array, we found MSA up-regulated miR-146a which directly targeted EGFR, whereas miR-146a inhibitor antagonized MSA-induced decrease of EGFR protein. We further used 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumor mice model to evaluate the inhibitory effect of MSA in vivo. MSA treatment significantly decreased the tumor burden and EGFR protein expression in tumor specimens. Furthermore, MSA treatment inhibited EGFR pathway and subsequntly reduced Interleukin-6 (IL-6) secretion in the supernatant of cancer cell lines. MSA-induced IL-6 suppression was EGFR-dependent. To further evaluate the association of IL-6 and the anti-tumor effect of MSA on esophageal cancer, we established the 4NQO-induced esophageal tumor model in IL-6 knock-out (IL-6 KO) mice. The results showed that IL-6 deficiency did not affect esophageal tumorigenesis in mice, but the inhibitory effect of MSA was abolished in IL-6 KO mice. In conclusion, our study demonstrated that MSA upregulated miR-146a which directly targeted EGFR, and inhibited EGFR protein expression and pathway activity, subsequently decreased IL-6 secretion. The inhibitory effect of MSA on esophageal cancer was IL-6 dependent. These results suggested that MSA may serve as a potential drug treating esophageal cancer.

Leiomyoma an uncommon benign esophageal tumor

Leiomyoma are rare esophageal masses. Majority remain asymptomatic but may present with dysphagia when more than five centimeters in size. Barium swallow is the initial diagnostic investigation. Small lesion can be observed. Symptomatic and large lesion should undergo prompt surgical enucleation. Here we presented a case of a 35 year old female presenting with progressive dysphagia and gradual weight loss for 5 years along with regurgitation for one year. Clinical examination was unremarkable. Barium study was suggestive of smooth intramural defect with normal mucosa. Computed tomography showed well defined homogenous opacity located intramuraly at the level of junction of middle and distal third of esophagus with normal surrounding structures. Surgical enucleation was done through a right posterolateral thoracotomy. Muscle defect was repaired and checked for possible leaks. Liquid diet was commenced on 5th postoperative day. Patient was discharged on semisolid diet for two weeks with progression to solid meal.

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: A case-control study.

e16027 Background: The pivotal goal of esophageal cancer (ESCA) screening is to identify early-stage cancer or precancerous lesions when curable treatments are available. Methylation of circulating-free DNA (cfDNA) has shown promising results in the early detection of multiple tumors recently. Here we conducted a prospective study to investigate the performance of cfDNA methylation in the early detection of ESCA. Methods: Specific methylation markers for ESCA were identified and optimized based on 24 esophageal tumor and its corresponding adjacent tissues. Age-matched participants with ESCA (n = 136), benign esophageal disease (n = 21) and healthy controls (n = 126) were randomized into the training and testing sets to develop an early-detection classifier. Results: In total, 921 differentiated methylation blocks (DMBs) between tumor and adjacent tissues were identified, of which 679 (73.7%) showed higher methylation level and 242 (26.3%) had lower methylation level in tumor tissues. In the training set, the specificity of the model built with these DMBs was 94.1% (95% CI, 85.5%−98.4%) and the sensitivity was 86.0% (95% CI, 72.2%−94.8%). The sensitives increased with stages, which were 77.8% (95% CI, 39.8%−97.2%), 90.9% (95% CI, 58.7%−99.8%), 83.3% (95% CI, 51.7%−97.9%) and 100.0% (95%CI, 63.1%−100.0%) for stage I-IV, respectively. Similar results were observed in the testing set with area under curve (AUC) of 0.932 (95% CI, 0.887−0.977). Conclusions: The cfDNA methylation profiles distinguished ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Consideration of the potential value of early detection in ESCAs, further evaluation in larger prospective studies is warranted.