Esophageal squamous cell carcinoma (ESCC) is one of the most fatal types of malignant tumors worldwide. Epitranscriptome, such as N6‐methyladenosine (m6A) of mRNA, is an abundant post‐transcriptional mRNA modification and has been recently implicated to play roles in several cancers, whereas the significance of m6A modifications is virtually unknown in ESCC. Analysis of tissue microarray of the tumors in 177 ESCC patients showed that higher expression of m6A demethylase ALKBH5 correlated with poor prognosis and that ALKBH5 was an independent prognostic factor of the survival of patients. There was no correlation between the other demethylase FTO and prognosis. siRNA knockdown of ALKBH5 but not FTO significantly suppressed proliferation and migration of human ESCC cells. ALKBH5 knockdown delayed progression of cell cycle and accumulated the cells to G0/G1 phase. Mechanistically, expression of CDKN1A (p21) was significantly up‐regulated in ALKBH5‐depleted cells, and m6A modification and stability of CDKN1A mRNA were increased by ALKBH5 knockdown. Furthermore, depletion of ALKBH5 substantially suppressed tumor growth of ESCC cells subcutaneously transplanted in BALB/c nude mice. Collectively, we identify ALKBH5 as the first m6A demethylase that accelerates cell cycle progression and promotes cell proliferation of ESCC cells, which is associated with poor prognosis of ESCC patients.

Background/Aim: The potential advantages of robot-assisted thoracoscopic esophagectomy (RATE) have yet to be verified. This study focused on the degree of lymph node dissection around the left recurrent laryngeal nerve (RLN). Patients and Methods: A total of 21 consecutive patients who received RATE (RATE group) and 38 who received conventional thoracoscopic esophagectomy (TE) (TE group), both with extended lymphadenectomy, for thoracic squamous cell esophageal carcinoma, were enrolled in this study. We compared the numbers of lymph nodes dissected from the mediastinum, especially around the left RLN. Results: The median number of lymph nodes dissected from around the left RLN was 6 in the RATE group and 4 in the TE group, and the ratio of the dissected lymph nodes around the left RLN to all lymph nodes was significantly higher in the RATE group (p=0.048). Conclusion: Our findings indicate that a robotassisted surgical system enables for more extensive dissection of lymph nodes around the left RLN.

High CXCL10 expression is an independent prognostic factor and has the potential to serve as a clinically useful marker of the need for adjuvant chemotherapy after surgery in patients with advanced thoracic ESCC.

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Background Despite wide acknowledgement of the importance of sarcopenia and prognostic markers such as the neutrophil-to-lymphocyte ratio, the impact on cancer patient survival of the timing of sarcopenia's emergence and its severity is not well understood, nor is the association between sarcopenia and prognostic markers. The aim of this study, therefore, was to investigate the effect of the severity and timing of changes in the psoas muscle index (PMI) on survival of advanced esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (NACRT) plus esophagectomy and the association between PMI and known prognostic markers. Methods Included in this study were 113 ESCC patients who underwent NACRT followed by esophagectomy. PMI and prognostic markers were measured at their initial visit, just before surgery (after NACRT), and 3 months postoperatively. Results All patients were classified into four groups according to the percent decrease in PMI after NACRT and after NACRT plus esophagectomy. Patients exhibiting a larger PMI decrease (C20%) after NACRT plus esophagectomy had significantly poorer overall survival than those showing a smaller PMI decrease. Furthermore, multivariable analysis showed that a larger decrease in PMI after NACRT plus esophagectomy was a significant risk factor for overall (P \ 0.0001) and recurrence-free (P = 0.0097) survival. Neither pretherapeutic PMI nor a decrease in PMI after NACRT significantly affected survival. PMI also showed weak, but significant, correlations with several prognostic markers postoperatively. Conclusions Decreased PMI after NACRT plus esophagectomy is a strong prognostic indicator in ESCC patients.

Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis has not yet been determined. Methods: Between 2008 and 2018, 94 ESCC patients diagnosed as clinical Stage III and 18 patients diagnosed as clinical Stage IVB with supraclavicular LN metastasis as the only distant metastatic factor were treated with NACRT followed by esophagectomy with extended lymph node dissection at Akita University Hospital. Long-term survival and the patterns of recurrence in these 112 patients were analyzed. Results: The median follow-up period of censored cases was 60 months. The five-year OS and DSS rates among the clinical Stage III patients were 57.6% and 66.6%, respectively. The five-year OS and DSS rates among the clinical Stage IVB patients were 41.3% and 51.6%, respectively. The most frequent recurrence pattern was distant metastasis (69.2%) in the Stage III patients and LN metastasis (75.0%) in the Stage IVB patients. Conclusion: NACRT followed by esophagectomy with three-field LN dissection is feasible and offers the potential for long-term survival of clinical Stage III ESCC patients and even clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. At least in patients with upper and middle thoracic ESCC, treating supraclavicular LNs as regional LNs seems to be appropriate.

Background Preoperative clinical diagnosis of lymph node (LN) metastasis and subsequent pathological diagnosis are often not in agreement. Detection of false-negative LNs is essential in selecting an optimal treatment strategy, and most importantly, the presence of false-negative LN is itself a significant prognostic indicator. Therefore, at present, there is an urgent need to establish more accurate and individualized evaluation methods for LN metastasis. Methods Of 213 cN0 patients who underwent curative esophagectomy without preoperative neoadjuvant treatment, 60 (28%) had LN metastasis diagnosed pathologically. There were 129 false-negative LNs, of which 85 were detectable by preoperative computed tomography (CT). We retrospectively investigated the distribution, frequency, and characteristics of pathologically positive nodes in patients with clinically N0 esophageal cancer. Results The paracardial region was the most frequent region of false-negative LNs, accounting for 26% (22 LNs) of the total incidence. False-negative LNs distributed widely from the neck to the abdomen in patients with a primary tumor in the middle thoracic esophagus. In patients with a primary tumor in the lower thoracic esophagus, four false-negative LNs were detected in the superior mediastinum. When the short-axis diameter, shape, and attenuation patterns of the LNs were used as criteria for metastasis diagnosis, they were insufficient for an accurate diagnosis. However, false-negative LNs in the most frequently occurring sites are characterized by smaller short-axis, suggesting that accurate diagnosis cannot be made unless the diagnostic criteria for the short-axis are reduced in addition to shape and attenuation. Conclusions Although restrictive to the most frequent regions of false-negative LNs occur, reducing size criterion and consideration of their shape and attenuation may contribute to improved diagnosis.

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