Background: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods: Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results: Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC. Conclusions: These results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.

Endoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD. Seven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia. En bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions. Use of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Background: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. Methods: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. Results: Fourteen patients were Child–Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI ≥67.0% group, OS was significantly better than in the 8-week RDI <67.0% group (p = 0.003). Conclusions: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

Background: Atezolizumab plus bevacizumab therapy has high response rates in patients with unresectable hepatocellular carcinoma (HCC). The hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) has been reported to be useful as an imaging biomarker for detecting β-catenin mutations. We evaluated whether the pretreatment of the hepatobiliary phase of EOB-MRI could predict the therapeutic effect of lenvatinib and atezolizumab plus bevacizumab. Methods: This study included 68 patients (lenvatinib group (n = 33) and atezolizumab plus bevacizumab group (n = 35)). The visual assessment and relative enhancement ratio (RER) of the largest HCC lesions were evaluated using the hepatobiliary phase of EOB-MRI. Results: The hyperintensity type (RER ≥ 0.9) was 18.2% in the lenvatinib group and 20.0% in the atezolizumab plus bevacizumab group. In the lenvatinib group, progression-free survival (PFS) was not different between the heterogeneous and homogenous types (p = 0.688) or between the hyperintensity and hypointensity types (p = 0.757). In the atezolizumab plus bevacizumab group, the heterogeneous type had significantly shorter PFS than the homogenous type (p = 0.007), and the hyperintensity type had significantly shorter PFS than the hypointensity type (p = 0.012). Conclusions: The hepatobiliary phase of EOB-MRI was useful for predicting the therapeutic effect of atezolizumab plus bevacizumab therapy on unresectable HCC.