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NADPH oxidases (NOXs) are transmembrane proteins that generate reactive oxygen species. Recent studies have reported that NOXs are involved in tumor progression in various cancers. However, the expression and role of NOX2 in esophageal squamous cell carcinoma (ESCC) remain unclear. This study aimed to clarify the pathophysiologic role of NOX2 in patients with ESCC and cell lines.Two human ESCC cell lines (TE5 and KYSE170) were used for NOX2 transfection experiments, and the effects on cell proliferation, cell cycle, cell motility, and cell survival were analyzed. An mRNA microarray analysis was also performed to assess gene expression profiles. Additionally, NOX2 immunohistochemistry was performed on 130 primary ESCC tumor samples to assess the prognostic value of NOX2 in patients with ESCC.NOX2 depletion significantly inhibited cell proliferation with the GNOX2 expression in ESCC cells affects tumorigenesis, especially cell cycle progression via the BTG2-related signaling pathway, as well as the prognosis of patients with ESCC. NOX2 may be a novel biomarker and therapeutic target for ESCC.

The clinical significance ofmiR-4257 in patients with colorectal cancer (CRC) remains unclear. Here, we investigated the usefulness of measuring miR-4257 levels in the plasma and cancer tissues of patients with CRC, and the function of miR-4257 in CRC cell lines.miR-4257 levels were measured in the plasma and cancer tissues of patients with CRC using quantitative polymerase chain reaction. The relationships between miR-4257 level and clinicopathological features were examined. Proliferation, transwell, wound healing, and adhesion assays were performed using a miR-4257 mimic and inflammatory cytokines.Relapse-free survival was significantly lower in patients with high miR-4257 levels in the plasma and cancer tissue (p0.001 andp=0.016, respectively). High miR-4257 expression was an independent predictive factor for recurrence (p=0.017 and p=0.028). Addition of inflammatory cytokines to CRC and normal cell lines increased the expression of miR-4257 in the cell lines and cell culture medium. Over-expression of miR-4257 in CRC cells increased malignancy, while over-expression in normal cells increased adhesion to CRC cells. The addition of inflammatory cytokines to normal cell lines enhanced adhesion to CRC cell lines.miR-4257 level in plasma and cancer tissues is a biomarker of disease recurrence in patients with CRC. Moreover, miR-4257 promoted tumour growth and was associated with cancer-induced inflammation.

Postoperative nutritional management for esophago-gastric junction cancer (EGJC) has become increasingly important. This study compared the nutritional status of patients with EGJC who underwent gastric tube reconstruction versus esophago-gastric anastomosis.Mediastinoscopic esophagectomy with gastric tube reconstruction was performed in 17 cases (group GT) and laparoscopic proximal gastrectomy with esophago-gastric anastomosis in 33 cases (group EG). The perioperative characteristics and nutritional status of the two groups in the 2 years postoperatively were compared.Group GT had a significantly higher level of serum total protein at 24 months postoperatively than did group EG. No other significant differences in postoperative nutritional status were observed between the groups.Gastric tube reconstruction for EGJC was not inferior to esophago-gastric anastomosis in terms of nutritional status. It is a candidate surgical procedure to avoid higher mediastinal anastomosis.

Background Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. Methods We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I–IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. Results Forty-eight (13.3%) colorectal cancer patients (Stages I–IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P P = 0.001, Hazard ratio 2.75, 95% CI: 1.54–4.73). Conclusions Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction.

Voltage-gated calcium channels form as a complex of several subunits, among which the function of CACNA2D1, one of the genes encoding the α2δ subunit, remains unclear. The aim of our study was to investigate the role of CACNA2D1 and evaluate the efficacy of amlodipine, a blocker of CACNA2D1, in the treatment of gastric cancer (GC).Knockdown experiments were performed on the human GC cell lines MKN7 and HGC27 using CACNA2D1 small interfering RNA (siRNA), and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical (IHC) analysis was conducted on samples obtained from 196 GC patients who underwent curative gastrectomy. In addition, the antitumor effects of amlodipine were investigated using a xenograft model.Cell proliferation, migration, and invasion were suppressed in CACNA2D1-depleted cells, and apoptosis was induced. The results of the microarray analysis showed that the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 in CACNA2D1-depleted cells. A multivariate analysis identified high CACNA2D1 expression levels, confirmed by IHC, as an independent poor prognostic factor in GC patients. Moreover, subcutaneous tumor volumes were significantly smaller in a xenograft nude mouse model treated with a combination of amlodipine and cisplatin than in a model treated with cisplatin alone.The present study indicates that CACNA2D1 regulates the apoptosis signaling pathway and may have potential as a biomarker for cancer growth and as a therapeutic target for GC.

To investigate the correlation between glycemic trends and cardiovascular risk after gastrectomy for gastric cancer.We enrolled 105 gastric cancer patients who underwent gastrectomy at our hospital between October 2017 and July 2020. Postoperative glucose concentrations, trends, and patterns were recorded using a continuous glucose monitoring (CGM) device. Cardiovascular risk was calculated using the Framingham stroke risk profile score (FSRPS), the Framingham risk score (FRS), and the Suita score. We examined the correlations between glycemic variability and cardiovascular risk scores.There were significant differences in the standard deviation (SD) of glucose levels between the high and low FSRPS groups (p = 0.049), the high and low FRS groups (p = 0.011), and the high and low Suita score groups (p = 0.044). The SD of glucose levels was significantly higher in patients with diabetes mellitus (DM) (p 0.001) and those who underwent total gastrectomy (TG) (p = 0.017). Additionally, the CGM data available for 38 patients 1 year post-gastrectomy were analyzed for glucose level dynamics, and the SD was found to be significantly higher than that at 1 month (p 0.001).Our findings suggest that long-term follow-up and therapeutic strategies tailored to glycemic trends may be necessary for gastric cancer patients after gastrectomy, especially those with DM and those who have undergone TG, to prevent cardiovascular events.

Background Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. Methods We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. Results A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P ≤ PLNR ≤ PLNR (P ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P P P P ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. Conclusion Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

Background Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, the transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, particularly around the aortic arch to the tracheal bifurcation, may increase the difficulty of this procedure. The present study aimed to clarify predictors of the difficulty of transcervical SCLN dissection. Methods Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of mediastinal narrowness by 3D-CT. The relationships between the difficulty of transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated. Results In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with difficulty. The median cervical angle and aorta distance were 15° and 33 mm in difficult cases and 19° and 43 mm in easy cases, respectively. In a multivariate analysis, the short aorta distance (odds ratio: 7.96, p = 0.002) and middle thoracic tumor (odds ratio: 3.35, p = 0.042) were independent predictive factors. Conclusions The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, a transhiatal approach should be combined for complete SCLN dissection.

BACKGROUND Transient receptor potential vanilloid 2 (TRPV2) is a highly Ca2+-permeable ion channel that is involved in a number of cellular processes. It is expressed in various human cancers; however, the role of TRPV2 in gastric cancer (GC) remains poorly understood. METHODS TRPV2 gene expression was knocked down in GC cell lines by small-interfering RNA (siRNA), and the biological roles of TRPV2 in the proliferation, migration, and invasion of GC cells were then investigated. The gene expression profile of GC was elucidated using a microarray analysis. TRPV2 expression in tumor tissue sections was analyzed by immunohistochemistry. RESULTS The migration and invasion abilities of GC cells were inhibited by the knockdown of TRPV2. Moreover, the microarray assay revealed that TRPV2 was associated with the transforming growth factor (TGF)-β signaling pathway. Immunohistochemical staining showed that the strong expression of TRPV2 correlated with lymphatic invasion, venous invasion, pathological T (pT), pathological N (pN), and a poor prognosis in GC patients. CONCLUSIONS TRPV2 appeared to promote tumor migration and invasion via the TGF-β signaling pathway, and the strong expression of TRPV2 was associated with a worse prognosis in GC patients.

Recent studies have highlighted the importance of understanding trends in blood glucose levels. We examined the differences in blood glucose fluctuations according to the reconstruction method used after distal gastrectomy (DG) in patients with non-diabetic gastric cancer (GC). Sixty-one patients who underwent DG followed by either Billroth 1 (B1) or Roux-en-Y (R-Y) reconstruction were enrolled in this study. We used flash continuous glucose monitoring (CGM), a new technique for assessing glycemic control, to document the post-gastrectomy glycemic profile. Immediately before discharge, a CGM sensor was placed subcutaneously to evaluate blood glucose trends for 2 weeks. The coefficient of variation of glucose levels was significantly higher in the Roux-en-Y (R-Y) group than in the Billroth I (B-I) group (p = 0.0260). The time below range (TBR, glucose levels of 30% (p = 0.006 and 0.042, respectively). Our findings provide new insights into the post-DG reconstruction method selected for patients with non-diabetic gastric cancer by assessing postoperative blood glucose fluctuations using flash CGM.

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA level in plasma has potential as a predictor of response to NAC. In the present study, we focused on miR-192-5p, which is highly expressed in EC tissue. The purpose was to investigate correlations between levels of plasma miR-192-5p and response to NAC. Furthermore, molecular functions of miR-192-5p associated with chemo-sensitivity were examined using EC cell lines. Level of miR-192-5p in plasma before surgery was evaluated in 113 EC patients. Sixty-nine patients received NAC. miR-192-5p levels in the CR group were significantly higher than the other groups (p = 0.002). Downregulation of miR-192-5p in EC cell line inhibited sensitivity to cisplatin, and overexpression of miR-192-5p in EC cell line promoted sensitivity to cisplatin. miR-192-5p regulated the sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR-192-5p may be used as a predictor of response to chemotherapy and prognosis in EC patients.

In transmediastinal esophagectomy (TME) with equivalent lymphadenectomy to transthoracic procedure, an understanding of surgical anatomy in the deep mediastinum near the aortic arch or tracheal bifurcation is essential for the safe procedure. The present study aimed to evaluate the bronchial arteries (BAs) with preoperative 3D-CT in TME. Seventy-nine patients with thoracic esophageal cancer undergoing TME were examined by preoperative 3D-CT to evaluate BA variations in the number, branching pattern, and mediastinal course. For the right BAs (RBAs) crossing the esophagus, the mediastinal courses in transcervical view were classified in relation to the esophagus and tracheobronchi and compared with surgical findings. A total of 107 RBAs (1.35/person) were confirmed on preoperative 3D-CT. Of these, 61 (57.0%) crossed the esophagus dorsally (type Ed), and the remaining 46 (43.0%) crossed the esophagus ventrally (type Ev). During the left transcervical procedure, all type Ed RBAs were identified and mostly preserved (57/61, 93.4%) whereas most type Ev RBAs were identified (39/46, 84.8%), but more than half were sacrificed (26/46, 56.5%) for lymphadenectomy. The blood loss during the transcervical procedure was 17.0 ± 55.8 ml. The total number of dissected mediastinal lymph nodes was 23.7 ± 9.3. There were no significant complications related to extensive lymphadenectomy. Preoperative 3D-CT evaluation is useful to understand the mediastinal courses of BAs specific to the transcervical approach, which may allow BAs to be handled more carefully according to the type during surgery, contributing to a safer procedure in the deep mediastinum.

The Na+/K+-ATPase alpha1 subunit (ATP1A1) is a critical component of Na+/K+-ATPase (NKA), a membrane pump that maintains a low intracellular Na+/K+ ratio and retains cellular volume and osmolarity. ATP1A1 was recently implicated in tumor behavior. Therefore, the present study investigated the role of ATP1A1 in patients with gastric cancer (GC). Knockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis. High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival. ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

Transmediastinal radical esophagectomy (TME) is the esophagectomy without thoracotomy that can achieve the mediastinal lymphadenectomy equivalent to transthoracic procedure. Understanding of surgical anatomy in the deep mediastinum near the aortic arch or tracheal bifurcation is essential for the safe procedure. The present study aims to evaluate the bronchial arteries (BAs) with preoperative 3D-CT for TME. Seventy-nine patients with thoracic esophageal cancer undergoing TME were examined by preoperative 3D-CT to evaluate BA variations in the number, branching pattern, and mediastinal course. For the right BAs (RBAs) crossing the esophagus, the mediastinal courses in transcervical view were classified in relation to the esophagus and tracheobronchi, and compared with surgical findings. A total of 107 RBAs (1.35/person) were confirmed on preoperative 3D-CT. Of these, 61 (57.0%) crossed the esophagus dorsally (type Ed), and the remaining 46 (43.0%) crossed the esophagus ventrally (type Ev). During the left transcervical procedure, all type Ed RBAs were identified and mostly preserved (57/61, 93.4%) whereas most type Ev RBAs were identified (39/46, 84.8%), but more than half were sacrificed (26/46, 56.5%) for lymphadenectomy. The blood loss during the transcervical procedure was 17.0 ± 55.8 mL. The total number of dissected mediastinal lymph nodes was 23.7 ± 9.3. There were no significant complications related to extensive lymphadenectomy. Preoperative 3D-CT evaluation is useful to understand the mediastinal courses of BAs specific to the transcervical approach, which may allow BAs to be handled more carefully according to the type during surgery, contributing to a safer procedure in the deep mediastinum.

Transthoracic esophagectomy (TTE) has been the standard procedure for esophageal squamous cell carcinoma (ESCC). In our institution, we performed transmediastinal esophagectomy (TME) as a radical operation for ESCC from 2013. In this study, we compared the short-term and long-term outcome of TME and conventional TTE using propensity score matching analysis. We performed a retrospective cohort study including 223 patients who underwent esophagectomy with gastric tube reconstruction for ESCC between January 2009 and December 2017. Of these, 115 patents underwent TME and 108 patients underwent TTE. Propensity score was calculated using logistic regression analysis and one-to-one patient pairs were matched using propensity score matching. 72 patients in the TME group and TTE group were extracted by propensity score matching. The incidence of postoperative pneumonia was significantly lower in the TME group (9.7% vs 33.3%, P = 0.0004). Three-year overall survival rate was relatively better in the TME group than in the TTE group (75.0% vs 62.6%, P = 0.165). And Three-year recurrence-free survival rate also tended to be better in the TME group than in the TTE group (55.2% vs 48.5%, P = 0.373). TME reduce postoperative pneumonia and may improve long-term prognosis in ESCC patients.

The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer and to identify predictive factors for subcarinal lymph node metastasis. Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail. The median number of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in patients (n = 49) with the primary lesion located in the upper thoracic esophagus. Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.

Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, especially around the aortic arch to tracheal bifurcation, may affect the difficulty. The present study aimed to clarify predictors for the difficulty of transcervical SCLN dissection. Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of the mediastinal narrowness by 3D-CT. The relationship between the difficulty of the transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated. In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with the difficulty. The median cervical angle (degree) and aorta distance (mm) were 15 and 33 in difficult cases, and 19 and 43 in easy cases, respectively. In a multivariate analysis, middle thoracic tumor (odds ratio: 3.28, p = 0.050) and a short aorta distance (odds ratio: 5, p = 0.036) were independent predictive factors. The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, transhiatal approach is essential for safe lymphadenectomy.

The left cervical approach with single-port mediastinoscopy is essential for radical esophagectomy without thoracotomy for esophageal cancer, which provides excellent visibility and handling along the esophagus to achieve radical lymph nodes (LNs) dissection in the upper and middle mediastinum. However, the transcervical procedure dissecting along the recurrent laryngeal nerve (RLN) requires careful use of both energy device for dissection and forceps for surgical field expansion to minimize the risk of RLN palsy. Using the left cervical approach, the LNs along the left RLN and tracheal bifurcation (subcarinal and bilateral main bronchial LNs) were dissected en bloc with the esophagus. The LNs along the right RLN were basically dissected through a right cervical incision under direct vision or dissected with the left cervical approach if visible. Intraoperative nerve monitoring (IONM) with NIM Response 3.0 was introduced to minimize the risk of RLN palsy. Continuous and intermittent IONMswere used for the left and right cervical procedures, respectively. Until March 2019, 175 patients underwent transmediastinal esophagectomy. Squamous cell carcinoma was predominant (93.7%). The upper and middle thoracic tumors were the most frequent (65.7%). Since IONM introduction, RLN palsy (grade I or more, CD classification) was significantly reduced. Without IONM (n = 106), the left RLN palsy was observed in 35.9%, while was in 13.6% with IONM (n = 66). In addition, the bilateral RLNs palsy was 14.2% without IONM, while was reduced to 3.0% with IONM. IONM is useful to reduce RLN palsy in transmediastinal esophagectomy. Especially, continuous IONM, which provides a real-time information on the risk procedure of RLN injury, is effective in preventing RLN palsy. The left cervical procedure with continuous IONM will be shown in movie.

Anterior gradient 2 (AGR2) promotes tumor growth and make a worse prognosis in several cancers, especially in adenocarcinoma. However, comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has not been reported. In the present study, the functional analysis and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples. AGR2 was upregulated in ESCC cell lines and ESCC tissue sample. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M-phase cells. Furthermore, phosphorylation of p53 in TP53-wild-type ESCC and osteosarcoma cells was also promoted. However, these changes were not observed in TP53-mutant ESCC cells. Immunohistochemistry results showed that high AGR2 and low p53 expression in ESCC tissue was correlated with a worse prognosis. These results suggest that although AGR2 enhances cell proliferation by inhibiting p53 phosphorylation in TP53-wild-type ESCC, the same mechanism does not regulate cell functions in TP53-mutant ESCC due to suppression of TP-53 function. In conclusion, AGR2 plays an important role in ESCC progression and might be a useful prognostic marker in patients with TP53-wild-type ESCC.

Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis.This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors.Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04).Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Background Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD. Methods This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC. Results Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups. Conclusions CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.

BACKGROUND Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score. METHODS A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS. RESULTS Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p

Background Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC). Method CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed. Results CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels. Conclusion The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.

BACKGROUND/AIM The regulation of gene expression by miRNAs plays an important role in cancer progression. Here, we investigated the role of miR-3663-3p in gastric cancer. PATIENTS AND METHODS The relationship between miR-3663-3p expression, clinicopathological features and prognosis were retrospectively analyzed in 80 gastric cancer patients. RESULTS miR-3663-3p expression was significantly lower in gastric cancer tissue than adjacent non-cancerous tissue (p=0.002). Recurrence free survival was significantly lower in patients with low miR-3663-3p expression (p=0.016). Low miR-3663-3p expression was also an independent predictive factor for recurrence (p=0.029). Overexpression of miR-3663-3p in gastric cancer cell lines significantly suppressed cell proliferation, migration/invasion, and induced G0/G1 arrest (p

Background/aim This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC). Patients and methods A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included. Results IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]. Conclusion The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM).

Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC.

The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for gastric cancer. The present study investigated ion channel expression profiles in gastric CSCs (GCSCs). Cells strongly expressing CD44 were separated from MKN74 cells, a human gastric cancer cell line, by fluorescence-activated cell sorting (FACS), and GCSCs were identified based on tumorsphere formation. Gene expression profiles in GCSCs were examined by a microarray analysis. Among MKN74 cells, CD44 messenger RNA levels were higher in CSCs than in non-CSCs. These CSCs also exhibited resistance to cisplatin. The microarray analysis revealed that the expression of several genes related to voltage-gated Ca2+ channels (VGCCs), including CACNA2D1 and CACNB4, was upregulated. The cytotoxicities of the CACNA2D1 inhibitor amlodipine and the CACNB4 inhibitor verapamil were greater at lower concentrations in CSCs than in non-CSCs, and markedly reduced tumorsphere numbers. Tumor volumes were significantly smaller in a xenograft nude mouse model treated with amlodipine or verapamil in combination with cisplatin than in that treated with cisplatin alone. The present results indicate that VGCCs play a role in maintaining CSCs, and demonstrated the potential of their specific inhibitors, amlodipine and verapamil, as targeted therapeutic agents against gastric cancer.

Chloride channel 2 (CLCN2) was recently shown to affect tumor behavior. The present study examined the functions of CLCN2 in the regulation of genes that play a role in tumor progression, as well as its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). Knockdown experiments were conducted using CLCN2-small-interfering RNA, and changes in proliferation, survival, and cellular movement in human ESCC cell lines were investigated. A microarray analysis of gene expression profiles in CLCN2-depleted ESCC cells was conducted. Fifty-four primary ESCC samples were examined by immunohistochemistry (IHC). The strong expression of CLCN2 was detected in TE5 and KYSE70 cells. Downregulated expression of CLCN2 enhanced proliferation and decreased apoptosis, whereas its upregulation inhibited proliferation and increased apoptosis. The effects of lubiprostone, a CLCN2 activator, were also investigated. In lubiprostone-treated cells, proliferation was inhibited and apoptosis was increased. The microarray analysis demonstrated that interferon (IFN) signaling-related genes were downregulated in CLCN2-depleted cells. IHC showed the presence of CLCN2 in the cytoplasm and cell membranes of ESCC cells. The prognostic analysis revealed a relationship between weak CLCN2 expression and shorter overall survival. The present results indicate that tumor progression is regulated by CLCN2 through its effects on IFN signaling. Furthermore, weak CLCN2 expression was associated with poorer outcomes in ESCC patients. The present study will contribute to a clearer understanding of the role of CLCN2 as a mediator of ESCC, as well as its use as a biomarker for this cancer.

A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.

Background The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer. Methods Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail. Results The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus. Conclusions Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.

The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty‐four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD‐L2 via interferon (IFN)‐related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD‐L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD‐L2 and binding ability to PD‐1 via IFN‐related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC., The depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in GC cells. This is the first report to clarify the mechanism of ANO9 regulating the immune escape of cancer cells via PD‐L2.

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.

Background Calcifying fibrous tumors (CFTs) are rare benign tumors. Because CFTs sometimes relapse, radical resection with adequate margins is necessary. We report a case of ileal CFT resected using single-port laparoscopic surgery. Case presentation A 33-year-old man presented with chief complaints of abdominal pain and vomiting. Computed tomography demonstrated a 45-mm-sized pelvic mass with partial calcification in the ileum. The patient was diagnosed with an ileal tumor, and partial resection of the ileum was performed using the single-port laparoscopic technique. Pathologic findings revealed hypocellular spindle cells with dense hyalinized collagen, interspersed calcification, and infiltration of lymphoplasmacytic cells. Immunohistochemical analysis showed that the factor XIIIa was positive and other tumor-specific markers were negative. Based on these findings, the tumor was finally diagnosed as a CFT. Conclusions Although CFT is benign, multifocal and recurrent CFTs have been reported. Therefore, careful intraperitoneal observation and curative resection are necessary. Single-port laparoscopic surgery is acceptable, both in terms of curability and minimal invasiveness.

Background/aim Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. Materials and methods We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. Results The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. Conclusion Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.

Few studies have reported the function and activation mechanism of ANO9 in esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the role of ANO9 in the regulation of tumor progression. Knockdown experiments with human ESCC cell lines were performed using ANO9 siRNA, and the effects on cell proliferation, the cell cycle, apoptosis, and cellular movement were analyzed. Immunohistochemistry (IHC) analysis was performed on 57 primary tumor samples obtained from ESCC patients. In an in vitro study, depletion of ANO9 reduced cell proliferation, invasion, and migration in KYSE150 and KYSE 790 cells. In the cell cycle analysis, depletion of ANO9 increased the number of cells in G0/G1 arrest. In addition, the knockdown of ANO9 increased apoptosis. The results of the microarray analysis indicated that various centrosome-related genes such as CEP120, CNTRL, and SPAST were up- or downregulated in ANO9-depleted KYSE150 cells. The IHC results showed that high expression of ANO9 was associated with poor prognosis. The results of the current study suggest that ANO9 regulates the cell cycle via centrosome-related genes in ESCC.

High-mobility group box-1 (HMGB1) is involved in a broad range of inflammatory responses and the progression of various types of malignancy. However, the roles of HMGB1 in the progression of esophageal squamous cell carcinoma (ESCC) are unclear. The aim of this study was to investigate the significance of intracellular and extracellular HMGB1 in ESCC. HMGB1 levels were measured in the tissue and plasma of patients with ESCC, or in ESCC cell lines and their conditioned medium. The effects of downregulation of intracellular HMGB1 or upregulation of extracellular HMGB1 on proliferation, cell migration, and invasion were evaluated using proliferation, transwell, and wound healing assays. Downregulation of HMGB1 expression inhibited cell proliferation, migration, and invasion. On the other hand, upregulation of extracellular HMGB1 level by addition of recombinant HMGB1 promoted the migratory and invasive abilities of ESCC cells through increases of phosphorylation of the signal-regulated kinase 1/2 and NF-κBp65 proteins. These effects of extracellular HMGB1 were attenuated by treatment with recombinant soluble thrombomodulin, which adsorbs HMGB1. The expression of HMGB1 was significantly higher in tumor tissue (p = 0.008), and the concentration of HMGB1 in the plasma was significantly higher in patients with ESCC than in healthy volunteers (p = 0.04). Cancer-specific survival was worse in patients with high concentration of plasma HMGB1 (p = 0.01). Increase of HMGB1 levels in tumor cells or plasma plays a crucial role in the malignant potential of ESCC. Intracellular and extracellular HMGB1 may be a therapeutic target in ESCC.

Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

Background/Aim: The prognostic nutritional index (PNI) is reported to affect postoperative complications and survival of patients with esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the clinical significance of PNI in treatment of ESCC. Patients and Methods: Two hundred and sixty-three patients who underwent radical esophagectomy were retrospectively analyzed. PNI was calculated in the pretreatment (pre-Tx), post-neoadjuvant chemotherapy (post-NAC), and postoperative periods. Results: Pre-Tx PNI positively correlated with prognosis irrespective of undergoing NAC (p

Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer-promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition of GC cells through the PI3K-Akt pathway and increased cell apoptosis in a TP53 mutation-independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor-malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC.

Anoctamin 5 (ANO5)/transmembrane protein 16E belongs to the ANO/ transmembrane protein 16 anion channel family. ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types. Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types. However, it remains unclear whether ANO5 acts as a plasma membrane chloride channel, and its expression and functions in gastric cancer (GC) have not been investigated.To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines, and changes in cell proliferation, cell cycle progression, apoptosis, and cellular movement were assessed. The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis. Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.Reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting demonstrated high ANO5 mRNA and protein expression, respectively, in NUGC4 and MKN45 cells. In these cells, ANO5 silencing inhibited cell proliferation and induced apoptosis. In addition, the knockdown of ANO5 inhibited GANO5 regulates the cell cycle progression by regulating the expression of cyclin-associated genes and affects the prognosis of patients with GC. These results may provide insights into the role of ANO5 as a key mediator in tumor progression and/or promising prognostic biomarker for GC.

As liver cancer (LC) is the sixth most commonly diagnosed malignancy, it is necessary to elucidate the molecular mechanisms responsible for LC progression. MicroRNAs (miRNAs/miRs) play crucial roles in tumor progression by regulating target gene expression. The present study assessed miRNA‑4730 expression and function in LC. The effects of miR‑4730 overexpression were examined in LC cell lines, and the target genes of miR‑4730 were evaluated using microarray analysis and TargetScan data. In addition, the association between miR‑4730 expression in tissue samples and the prognosis of 70 patients with LC was evaluated. miR‑4730 expression was suppressed in LC tissues and cell lines. miR‑4730 overexpression suppressed cell proliferation and cell cycle progression and promoted apoptosis. High mobility group A1 (HMGA1) was revealed as the direct target of miR‑4730 using luciferase reporter assay, and the inhibition of downstream integrin‑linked kinase (ILK) expression and Akt or glycogen synthase kinase 3β (GSK3β) phosphorylation was confirmed. The lower expression of miR‑4730 in tissue samples was significantly associated with a worse recurrence‑free survival of patients with LC. On the whole, miR‑4730 suppressed tumor progression by directly targeting HMGA1 and inhibiting the ILK/Akt/GSK3β pathway. miR‑4730 thus has potential for use as a prognostic marker and may prove to be a therapeutic target for miRNA‑based therapies.

A 71-year-old woman was referred to our hospital because of an esophageal submucosal tumor. Esophagogastroduodenoscopy revealed a submucosal tumor of 40×25 mm with ulceration in the lower thoracic esophagus and endoscopic ultrasonographic fine needle aspiration histology showed KIT(+), CD34(+), DOG-1(+), desmin(-), S-100 protein(-). We diagnosed esophageal GIST and performed mediastinoscope-assisted transhiatal esophagectomy with gastric tube reconstruction. Histopathological findings showed c-kit(+), Ki-67 index of 8%, and middle-risk GIST by the modified- Fletcher classification. Mediastinoscope-assisted transhiatal esophagectomy is useful in terms of shortening total operative time and preventing respiratory complications because it does not require thoracic operation, one-lung ventilation, or repositioning. Subtotal esophagectomy under a mediastinal approach could secure a margin for resection, which may reduce the risk of recurrence, and could be one of the surgical procedures for esophageal GIST.

A 66-year-old man presenting with melena was diagnosed with rectosigmoid cancer and underwent laparoscopic high anterior resection. Intraoperative findings showed that the descending colon did not adhere to the retroperitoneum and was largely displaced inward, and the descending and sigmoid colon extensively and strongly adhered to the small intestinal mesentery, as predicted prior to surgery. The patient was diagnosed with persistent descending mesocolon(PDM). The first sigmoid artery diverged from the left colonic artery; however, ligation of supplying arteries under laparoscopy was perceived as a risk for marginal artery injury due to the shortening of the mesentery by PDM. Therefore, the sigmoid artery and inferior mesenteric vein were ligated directly from the umbilical wound. No postoperative complications were observed, and the patient was discharged 9 days after the surgery. Although PDM has not been defined, it has been reported that preoperative prediction is possible depending on the positional relationship between the descending colon and the left kidney. In this case, we performed the surgery after taking into consideration the anatomical features assessed preoperatively, leading to a safe operation.

The significance of spirometry as preoperative risk assessment for gastrointestinal surgery has been controversial. At the beginning of the COVID-19 pandemic, preoperative spirometry was temporarily suspended in our institute. This study was aimed to investigate the necessity of spirometry for gastrointestinal cancer surgery.We compared short-term postoperative outcomes between 318 patients who underwent surgery for colorectal or gastric cancer with (Spirometry group; n=272) or without spirometry (Non-spirometry group; n=46).Respiratory functional disorders were detected in 77 (28.3%) patients in the Spirometry group. No significant differences were noted in complications, including pneumonia, or the length of hospital stay between the two groups. An advanced age, male sex, comorbidities with respiratory diseases, and a smoking history significantly correlated with abnormal results in spirometry.Preoperative spirometry may be substituted with other clinical factors in patients with gastrointestinal cancer.