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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.

Objectives Recent findings suggest that the combination of mechanical bowel preparation (MBP) and preoperative oral antibiotics (OA) decreases the risk of surgical site infection (SSI) in colorectal surgery; however, this remains controversial. The present study examined the efficacy of OA plus MBP in laparoscopic colorectal cancer (CRC) surgery using propensity score matching (PSM). Methods A total of 1080 patients with CRC underwent MBP followed by laparoscopic surgery between 2007 and 2019. OA was administered to all patients with CRC who underwent colectomy from 2018. PSM was performed to compare the effects of OA plus MBP (OA) versus MBP only (non-OA) on the rate of superficial SSI. Results Overall, 128 patients received OA. Significant differences were observed in age, the American Society of Anesthesiologists performance status (ASA-PS), liver disease, and preoperative serum albumin (Alb) between the OA and non-OA groups. The enrolled patients were matched using PSM into two groups based on the following factors: sex, age, body mass index, ASA-PS, diabetes mellitus, liver disease, Alb, and tumor location, which resulted in the disappearance of significant differences. A univariate analysis showed that blood loss of 100 g or more, non-OA, and preoperative chemotherapy or radiation correlated with SSI (p = 0.021, 0.010, 0.038). A multivariate analysis of these three variables identified blood loss of 100 g or more and non-OA as independent risk factors for SSI (hazard ratio (HR): 3.238, p = 0.031; HR: 2.547, p = 0.033). Conclusions The present study revealed that OA plus MBP markedly reduced SSI rate. OA with MBP needs to be adopted in laparoscopic CRC surgery.

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.

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/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).

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.

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.

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.

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.

The prognosis of gastric cancer patients with peritoneal dissemination is extremely poor and effective treatment for peritoneal dissemination has not been established. Gastric cancer-derived small extracellular vesicles play an important role in the development of a favorable microenvironment for peritoneal metastasis and progression of peritoneal dissemination. Here, we aimed to investigate the transformation of gastric cancer cells by removing gastric cancer-derived small extracellular vesicles and to develop a novel therapy for inhibiting peritoneal dissemination.Gastric cancer cells were cultured in medium containing gastric cancer- and peritoneal mesothelium-derived small extracellular vesicles and in medium from which small extracellular vesicles were removed by ultracentrifugation. Cell function assays were performed in vitro, and the alternations in gene expression in gastric cancer cells were analyzed. The inhibitory effect of intraperitoneal lavage on peritoneal dissemination was investigated in vivo as a method to remove gastric cancer-derived small extracellular vesicles.Removal of gastric cancer-derived small extracellular vesicles suppressed the proliferative and migrative abilities of gastric cancer cells and the adhesion of gastric cancer cells to peritoneal mesothelial cells. It altered the expression of several genes related to the cell cycle and epithelial-mesenchymal transition pathways of gastric cancer cells, leading to the inhibition of gastric cancer cell growth and peritoneal dissemination in vivo.Our study provides novel insights into a novel therapy for inhibiting the peritoneal dissemination of gastric cancer by targeting gastric cancer-derived small extracellular vesicles to improve the prognosis of gastric cancer patients with peritoneal metastasis.

INTRODUCTION Seprafilm® has been used to prevent postoperative adhesion. However, it is challenging to insert and apply Seprafilm during laparoscopic surgery because of its fragility and sticky nature caused by moisture. Some studies have reported how to apply Seprafilm into a surgical site during laparoscopic surgery; however, some required special equipment with additional costs, and some were technically difficult to use. Herein, we introduced our simple method for applying Seprafilm during laparoscopic surgery. MATERIAL AND SURGICAL TECHNIQUE Seprafilm was cut into three equal rectangle-shaped pieces and left to absorb moisture for a few minutes. All three pieces of Seprafilm were placed on the gauze, and the gauze was folded in half and grasped by forceps. The gauze with Seprafilm was inserted through a 12-mm trocar and placed at the surgical site close to the target place. The gauze functioned as a working station and prevented Seprafilm from directly attaching to the surrounding tissue, which allowed the surgeons to handle it with ease. The gauze was used to press Seprafilm onto the target area and could be easily removed through a 12-mm trocar. Through this method, Seprafilm was successfully applied in all cases and the average time of applying one sheet was 100 seconds. There was no small bowel obstruction within 30 days after surgery. DISCUSSION This method neither requires special training nor special equipment only used for Seprafilm. Moreover, it can be easily introduced to every surgeon for the application of Seprafilm during laparoscopic surgery.

Background: Breast cancer often metastasizes to the lungs, bones, liver, and brain, colon metastasis from breast cancer (CMBC) is extremely rare. Case Report: The patient was a 63-year-old female. Mastectomy had been performed for breast cancer (pStage IIB) 15 years earlier at another hospital. Metastasis to the lumbar spine had been detected 4 years prior to referral to us and the patient had undergone hormonal therapy with an aromatase inhibitor. Furthermore, early primary sigmoid colon cancer had been endoscopically resected 2 years before referral. The patient was diagnosed with cancer recurrence in the colon at follow-up examinations performed 2 years after that endoscopic resection. After referral to our hospital, laparoscopic sigmoidectomy was performed. Based on the histopathological examination and immunohistological staining results (positive for cytokeratin 7, GATA-binding protein 3, estrogen receptor and human epidermal growth factor receptor-related 2 (2+); negative for cytokeratin 20, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15 and caudal-related homeobox 2) the final pathological diagnosis was CMBC. Conclusion: Although extremely rare, the possibility of CMBC should be considered in the case of colonic tumors in patients with a history of breast cancer.

Recent studies identified that low levels of tumor suppressor microRNAs in plasma/serum relate to tumor progression and poor outcomes in cancers. This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in gastric cancer (GC) patients to clarify their potential as novel biomarkers and therapeutic targets. We focused on five candidates (miR-148a, miR-101, miR-129, miR-145 and miR-206) of tumor suppressor miRNAs in GC by a systematic review of NCBI database. Of these, miR-148a levels were significantly down-regulated in plasma of GC patients compared to healthy volunteers by test- and validation-scale analyses (P

Background/Aim: The self-expanding metallic stent (SEMS) has recently been used for obstructive colorectal cancer (OCRC), and reports of its use are increasing. However, the long-term results of OCRC after using SEMS remain unclear. This study investigated the characteristics of SEMS compared to trans-anal tube (TAT) and clarified the long-term results and efficacy of SEMS for OCRC. Patients and Methods: We analyzed 48 patients who required SEMS or TAT for emergent decompression of OCRC and underwent resection for OCRC between 2007 and 2019. The perioperative factors and long-term results in the two groups were evaluated. Results: Patients with OCRC were divided into the SEMS (n=23) and the TAT group (n=25). No significant differences were seen in background factors, complications and the 5-year overall survival after surgery (p=0.3500) between the two groups. The clinical success of decompression (p=0.0072), oral intake (p

Background/aim We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group. Patients and methods A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS). Results The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS. Conclusion The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group.

Background: The Geriatric Nutritional Risk Index (GNRI) is a nutritional measure for predicting the risk of morbidity and mortality in hospitalized patients. We evaluated the utility of the GNRI to predict the short-term and long-term outcomes after curative surgery for gastric cancer (GC). Patients and Methods: Patients who underwent curative surgery for GC between 2008 and 2016 were reviewed (n=795). We classified patients into two groups according to the GNRI (high GNRI: low and no risk; low GNRI: major and moderate risk) and compared the utility of the GNRI. Results: A low GNRI was an independent prognostic factor for poorer overall survival (hazard ratio=2.34, p0.001). The GNRI tended to be a better prognostic indicator in elderly patients with GC. Low GNRI was associated with postoperative complications (odds ratio=2.27, p=0.002), especially in patients aged ≥75 (odds ratio=2.26, p=0.042). Conclusion: Low GNRI was associated with poor prognosis and occurrence of postoperative complications in patients with GC, especially in elderly patients.

The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence. Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups. The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence. Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy.

Background: Adjuvant chemotherapy (AC) following curative gastrectomy for stage II/III gastric cancer (GC) is recommended in Japan. However, for various reasons, patients cannot always start AC at the appropriate time. This study was designed to investigate the effect of the postoperative interval until adjuvant chemotherapy (PIAC) and cumulative S-1 dose on prognosis. Methods: Between 2008 and 2014, consecutive 81 GC patients who underwent postoperative S-1 monotherapy were enrolled in this study. Results: Postoperative complications of Clavien-Dindo grade II or higher and postoperative peak C-reactive protein of 8.1 mg/dl or higher were significantly associated with delayed AC. The cut-off value of PIAC selected to most effectively stratify prognosis was 7 weeks. For relapse-free survival (RFS), patients with PIAC ≥ 7 weeks had an insignificantly poorer prognosis than those with PIAC < 7 weeks. A multivariate analysis showed that PIAC ≥ 7 weeks [p = 0.024; hazard ratio (HR) 2.45] and the cumulative S-1 dose/body surface area (BSA) ≥ 12,000 mg/m2 [p = 0.004; HR 3.27] were independent prognostic factors. In patients with the cumulative S-1 dose/BSA ≥ 12,000 mg/m2, there were no prognostic differences between patients with and without PIAC ≥ 7 weeks. Conclusions: Seven weeks after surgery could be a limit indicator starting AC. A cumulative S-1 dose/BSA of more than 12,000 mg/m2 might be a key dose for diminishing the poor prognostic effects of delaying AC.

Background: The clinical significance of metastasis in inferior mesenteric artery (IMA) lymph node in patients with left-sided colorectal cancer (LCRC) is unclear. The aim of this study was to investigate the impact of IMA lymph node metastasis (IMA-LN (+)) on the prognosis of patients with LCRC. Methods: A total of 292 patients with stage III LCRC and 111 patients with stage IV LCRC who underwent radical resection of the primary tumor between 2005 and 2016 were included. The clinicopathological features and prognosis, which were retrospectively obtained from medical records, were compared regarding IMA-LN (+). Results: IMA-LN (+) was observed in 10 patients with stage III LCRC (2.3%). Moreover. ≥4 metastatic lymph nodes (p = 0.001) and poorly differentiated type (p = 0.049) were more frequently observed in patients with IMA-LN (+) than in patients without IMA lymph node metastasis (IMA-LN (-)) in stage III; IMA-LN (+) patients had significantly worse overall survival (OS) than IMA-LN (-) patients in stage III (p = 0.015). Conversely, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients (p = 0.192). Likewise, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients with distant metastatic lymph nodes only (n = 12) (p = 0.294). Conclusion: The prognosis of IMA-LN (+) patients was worse than that of IMA-LN (-) patients in stage III LCRC; moreover, it was similar to that of patients with stage IV LCRC.

Background Diffusion-weighed MRI (DWI) has the potential to reveal intra-tumor pathological heterogeneity consisting of the stroma. The present study investigated the value of intra-tumor heterogeneity evaluated by DWI for predicting the survival of patients with lower rectal cancer (LRC). Methods A total of 172 LRC patients underwent radical surgery between 2009 and 2017. Patients with T1 tumors, distant metastasis, and no pre-operative MRI were excluded. Fifty-eight cases were targeted. Intra-tumor heterogeneity on DWI was quantified by an image analysis (MRI heterogeneous score of DWI: mrHSD). All enrolled cases were divided into two groups (high and low groups) according to median mrHSD. Results Median mrHSD was 0.457 (0.170–0.823), with a higher score indicating a more heterogeneous pattern on DWI. The frequency of a clinical diagnosis of lymph node metastasis and extramural vascular invasion was higher in the high group. Three-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the low group than in the high group (OS: 100% vs 84.6%, p = 0.012; RFS: 85.9% vs 55.6%, p = 0.027). A univariate analysis of RFS showed that the RFS rates of poorly differentiated LRC, a positive circumferential resection margin on MRI, and high mrHSD were worse (p = 0.097, 0.086, and 0.049). A multivariate analysis revealed that high mrHSD tended to be an independent factor for predicting post-operative recurrence (HR: 2.836, p = 0.060). Conclusion The quantitative evaluation of intratumor heterogeneity on DWI has potential as an imaging biomarker for predicting post-operative recurrence.

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

// Kenichi Aratani 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Takuma Ohashi 1 , Mahito Miyamae 1 , Wataru Okajima 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Keiji Nishibeppu 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Hitoshi Tsuda 2, 3 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan 2 Department of Pathology, National Cancer Center Hospital, Tokyo, Japan 3 Department of Basic Pathology, National Defense Medical College, Saitama, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: adenocarcinoma of the esophagogastric junction, gastric cancer, CTEN, prognosis, oncogene Received: April 19, 2017 Accepted: September 04, 2017 Published: September 20, 2017 ABSTRACT Background: To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether C-terminal tensin-like (CTEN), a member of the tensin gene family and frequently overexpressed in various cancers, acts as a cancer-promoting gene through overexpression in AEG. Materials and Methods: We analyzed 5 gastric adenocarcinoma (GC) cell lines and 104 primary AEG tumors curatively resected in our hospital between 2000 and 2010. Results: CTEN overexpression was detected in GC cell lines (2/5 cell lines; 40%) and primary AEG tumor samples (35/104 cases; 34%). CTEN knockdown using several specific siRNAs inhibited the proliferation, migration, and invasion of CTEN-overexpressing cells. CTEN overexpression was significantly correlated with more aggressive venous and lymphatic invasion, deeper tumor depth, and higher rates of lymph node metastasis and recurrence. Patients with CTEN-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors ( P < 0.0001, log-rank test) in an expression-dependent manner. CTEN positivity was independently associated with a worse outcome in the multivariate analysis ( P = 0.0423, hazard ratio 3.54 [1.04–16.4]). Conclusions: CTEN plays a crucial role in tumor cell proliferation, migration, and invasion through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG.

// Taisuke Imamura 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Mahito Miyamae 1 , Wataru Okajima 1 , Takuma Ohashi 1 , Jun Kiuchi 1 , Keiji Nishibeppu 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Kazuma Okamoto 1 , Hitoshi Fujiwara 1 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: gastric cancer, tumor suppressor microRNA, plasma, biomarker Received: April 16, 2017 Accepted: August 15, 2017 Published: September 13, 2017 ABSTRACT Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC). Results: The miR-101 expression level was significantly lower in GC tissues ( P = 0.0038) and GC cell lines ( P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers ( P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients ( P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06–11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1. Conclusions: Depletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.

Hepatocellular carcinoma (HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called "liquid biopsy" is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0929-3) contains supplementary material, which is available to authorized users.

The precision of magnet alignment in next-generation light sources is critical. To achieve this, the multipole magnets on a common girder of SPring-8-II, an upgrade of SPring-8, are planned to be aligned using the vibrating-wire technique. We developed an alignment monitoring system to monitor the magnet positions in the tunnel where the vibrating-wire technique cannot be executed while the magnets are not energized or when there are vacuum chambers in the magnet center. The alignment monitoring system utilizes a non-contact capacitive sensor embedded in a ceramic ball to measure the wire position relative to the center of the ball and derives the wire sag by measuring a higher mode eigenfrequency. The constitution of this system is illustrated for relevant studies, including the investigation of wire sag against the eigenfrequency, observation of the actual wire sag at a test bench, and validation of the system on the girders for the prototype magnets of SPring-8-II. The system measured the positions of a series of magnets with a precision of ±4 µm (peak to peak) in a 4 m range, in both the horizontal and vertical directions, meeting the requirement of SPring-8-II.

Background: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine–threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods: We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P

// Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Tsutomu Kawaguchi 1, * , Hiroki Takeshita 1 , Mahito Miyamae 1 , Takuma Ohashi 1 , Wataru Okajima 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: plasma, microRNA, biomarker, prognosis, chemoresistance Received: March 27, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT BACKGROUND: This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach. RESULTS: (1) Four candidate microRNAs ( miR-223, 103a, 23b and 23a ), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT–PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro . (5) A high level of plasma miR-23a , which tended to correlate with lymphatic invasion ( p = 0.0808) and deep depth of invasion ( p = 0.0658), was an independent risk factor for chemoresistance in ESCC ( p = 0.0222; odds ratio: 12.4; range 1.46–105). MATERIALS AND METHODS: We used the Toray ® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil. CONCLUSIONS: Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.

// Wataru Okajima 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Mahito Miyamae 1 , Tsutomu Kawaguchi 1 , Shoji Hirajima 1 , Takuma Ohashi 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Ryo Moriumura 1 , Hisashi Ikoma 1 , Kazuma Okamoto 1 , Hiroki Taniguchi 2 , Yoshito Itoh 3 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan 2 Department of Surgery, Kyoto Second Red Cross Hospital, Haruobicho, Kamigyo-ku, 602-8026, Kyoto, Japan 3 Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: plasma, circulating microRNA, liquid biopsy, liver cirrhosis, tumor marker Received: February 17, 2016 Accepted: July 09, 2016 Published: July 22, 2016 ABSTRACT Aims: This study was designed to identify novel microRNAs (miRNAs) in plasma for detecting and monitoring hepatocellular carcinoma (HCC), independent of hepatic function and background liver diseases with different etiologies. Results: (1) Four oncogenic miRNAs (miR-151, 155, 191 and 224) with high expression in HCC tissues were selected as candidates. (2) Quantitative RT-PCR using plasma samples from 107 HCC patients and 75 healthy volunteers revealed a significantly higher level of plasma miR-224 in HCC patients than in healthy volunteers according to a small-scale analysis (P < 0.0001), two independent large-scale cohort analysis (P < 0.0001, AUC 0.908). (3) miR-224 expression was significantly higher in HCC tissues and HCC cell lines than in normal hepatic tissues and fibroblasts, respectively. (P = 0.0011, 0.0150) (4) Plasma miR-224 reflected tumor dynamics; preoperative plasma levels of miR-224 were significantly reduced in postoperative samples (P = 0.0058), and plasma miR-224 levels were significantly correlated with paired miR-224 levels in HCC tissues (P = 0.0005). (5) Furthermore, plasma miR-224 levels significantly discriminated HCC patients from patients with chronic liver disease (P = 0.0008). A high plasma miR-224 level was significantly correlated with larger tumor size (P = 0.0005) and recurrences (P = 0.0027). The plasma miR-224 level could accurately detect small tumors less than 18 mm preoperatively. Methods: We performed a systematic review of the NCBI database and selected candidate miRNAs reported as highly expressed in HCC tissue. Conclusions: Plasma miR-224 may be a sensitive biomarker for screening HCC and monitoring tumor dynamics.

YEATS domain containing 4 (YEATS4) has functions of chromatin modification and transcriptional regulation and is in a gene-amplified region (12q13) in various human cancers. In this study, we tested whether YEATS4 acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 5 GC cell lines and 135 primary tumor samples of GC, which were curatively resected in our hospital. Overexpression of the YEATS4 protein was frequently detected in GC cell lines (5/5 cell lines, 100%) and primary GC tumor tissues (32/135 cases, 23.7%). Knockdown of YEATS4 inhibited proliferation, migration and invasion of GC cells through NOTCH2 down-regulation in a