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To assess the severity of preoperative myopenia and myosteatosis in pediatric patients with inflammatory bowel disease (IBD) and examine their impact on postoperative complications.The subjects of this retrospective study were 30 pediatric patients with IBD (22 with ulcerative colitis (UC) and 8 with Crohn's disease (CD)) and 67 age-matched controls. Preoperative body mass index (BMI), psoas muscle index (PMI), and intramuscular adipose tissue content were compared between the patient groups, to investigate their association with postoperative complications.BMI and PMI were significantly lower in the IBD patients than in the controls (p 0.0001, p 0.0001, respectively). CD was associated with significantly lower BMI and PMI (p = 0.01, p = 0.01, respectively) than UC. Intramuscular adipose tissue content was comparable between the IBD patients and the controls and between the UC and CD patients. There were no significant differences among the three indices in relation to the presence or absence of postoperative complications in patients with IBD. When limited to surgical site infection (SSI), only PMI was significantly lower in the patients with SSI than in those without SSI (p = 0.04).Although BMI and PMI were lower preoperatively in pediatric IBD patients than in controls, only myopenia seemed to affect the development of SSI.

Background Our previous study identified methicillin-resistant Staphylococcus aureus (MRSA) colonization as an independent risk factor for neonatal surgical site infection. Here we introduce intraoral breast milk application (IBMA) during a fasting state to prevent MRSA colonization. We aimed to evaluate both the risk factors for MRSA colonization and the efficacy of IBMA in neonatal surgical patients. Methods A retrospective review was performed using admission data from 2007 to 2016. Neonatal patients who underwent surgery and were tested periodically for MRSA colonization were evaluated for an association between MRSA colonization and perinatal or perioperative factors. Results The overall incidence of MRSA colonization for the 159 patients enrolled in this study was 16.4%. Univariate analysis showed that MRSA colonization was significantly more frequent in the following patients: those with Down syndrome, those admitted on their day of birth, those in need of fasting immediately after birth, and those not receiving IBMA. Multivariate analysis showed that comorbid Down syndrome was an independent risk factor (hazard ratio: 4.6; 95% confidence interval: 1.2-19.5, P = 0.03) and implementation of IBMA was an independent preventive factor for MRSA colonization (hazard ratio: 0.4; 95% confidence interval: 0.1-0.9, P = 0.04). MRSA-positive patients admitted significantly earlier and stayed longer preoperatively than MRSA-negative patients. Conclusions In neonates undergoing surgery, and patients with Down syndrome, early diagnosis after birth and a long waiting period before operation may be associated with MRSA colonization. Intraoral breast milk application may be beneficial for preventing MRSA colonization.

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Background The predictive factors for chronic pouchitis after ileal pouch–anal anastomosis (IPAA) in pediatric-onset ulcerative colitis (UC) remain unclear. This study evaluated the predictive factors for chronic pouchitis after IPAA in patients with pediatric UC. Methods The data from 52 patients with pediatric-onset UC who underwent IPAA in Mie University Hospital were retrospectively reviewed. The endoscopy surveillance was performed yearly or at the timing of the symptom. Chronic pouchitis was defined as antibiotic-dependent/-refractory and relapsing cases. Potential predictors of chronic pouchitis were analyzed. Results During the first 5 years after IPAA, pouchitis was identified in 32.7%. Of these patients, 12 (70.6%) developed chronic pouchitis. The predictor of chronic pouchitis was a preoperative history of immunomodulator use before IPAA (p = 0.04). Life table analysis revealed that patients with chronic pouchitis tended to develop pouchitis earlier after IPAA than did patients without chronic pouchitis (p = 0.012). Receiver operating characteristic curve analysis showed that the occurrence of pouchitis within 15 months after IPAA surgery predicted the development of chronic pouchitis (sensitivity, 92%; specificity, 80%). Conclusion In pediatric patients with UC, the predictive factors for chronic pouchitis are immunomodulator use and early occurrence of the first episode of pouchitis within 15 months after IPAA. Level of evidence III

Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor-associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinicopathological characteristics of patients with CRC was analyzed. A total of 139 surgical specimens from patients with CRC and 36 patients with benign colonic disease undergoing surgery at Mie University Hospital were analyzed. HSP47 gene expression was determined by reverse transcription quantitative PCR using Power SYBR Green PCR methods. Expression level of HSP47 was significantly higher in CRC tissues compared with normal tissue from patients with benign colonic disease. Furthermore, high HSP47 expression was significantly associated with tumor progression, including high T stage, lymph node metastasis and venous invasion, and high TNM stage. High HSP47 expression may therefore serve as a novel predictive biomarker for determining patients with CRC and LN metastasis. According to Kaplan-Meier analysis, patients with high HSP47 expression level had significantly poorer overall survival than those with low HSP47 expression level. Furthermore, multivariate analyses identified HSP47 expression as an independent predictive marker for LN metastasis and poor overall survival in patients with CRC. In summary, the present study demonstrated that HSP47 expression may be considered as a novel biomarker for predicting LN metastasis status and prognosis in patients with CRC.

Establishment of evidence-based best practices for preventing surgical site infection (SSI) in neonates is needed. SSI in neonates, especially those with a low birth weight, is potentially life-threatening. We aimed to identify risk factors associated with SSI in neonates. A retrospective review was performed using 2007–2016 admission data from our institution. Neonatal patients who were admitted to the neonatal intensive care unit and underwent surgery were evaluated for a relationship between development of SSI and perinatal or perioperative factors and methicillin-resistant Staphylococcus aureus (MRSA) colonization during hospitalization. One hundred and eighty-one patients were enrolled in this study. Overall SSI incidence was 8.8%. Univariate analysis showed that SSI was significantly more frequent in both patients with contaminated or dirty wound operations and patients with MRSA colonization during hospitalization. Both of these factors were identified as independent risk factors for SSI by multivariate analysis [hazard ratio (HR): 6.1, 95% confidence interval (CI) 2.0–19.9; HR: 3.3, 95% CI 1.1–10.4, respectively]. This study identified contaminated or dirty wound operations and MRSA colonization during hospitalization as risk factors for SSI in neonates. MRSA colonization may be a preventable factor, unlike previously reported risk factors.

In neonatal surgical patients requiring an enterostomy, there is no definitive recommendation regarding the ideal enterostomy location: at the edge of the primary incision or at a different incision. We retrospectively reviewed 2005–2017 administration data in our institution. All neonatal patients who underwent contaminated or dirty wound laparotomy and enterostomy construction were evaluated regarding the enterostomy location, occurrence of postoperative incisional surgical-site infection (SSI) at the primary incision, and stoma-related complications. Patients were divided into two groups based on stoma location: at the primary incision (the same incision group: SI group, n = 16) or at another incision (different incision group: DI group, n = 23). We performed 2 jejunostomies, 13 ileostomies, and 1 colostomy in the SI group, and 4 jejunostomies, 18 ileostomies, and 1 colostomy in the DI group. One of 16 patients (6.3%) in the SI group and 2/23 patients (8.7%) in the DI group experienced superficial incisional SSI, with comparable SSI incidence between groups (p = 0.78). Every SSI did not result in stoma-related complications. Although the enterostomy location did not influence the incidence of laparotomy wound infection in this study, prospective studies are mandatory to fully assess the safety of enterostomy construction at the edge of the primary incision.

Background/purpose The purpose of this study was to explore clinical characteristics and primary surgical diagnoses associated with in-hospital death in pediatric surgical patients admitted to the neonatal intensive care unit (NICU) of a tertiary hospital. Methods This retrospective study includes all patients admitted to our NICU for pediatric surgical diseases between January 2001 and December 2015. Univariate and multivariate binary logistic regression were performed to assess independent factors associated with in-hospital death. Results A total of 440 cases were included and 334 (83.5%) patients underwent one or more surgeries. Thirty six patients (8.2%) died while hospitalized in the NICU. The 5 most common surgical diagnoses were intestinal atresia/stenosis, anorectal malformation, congenital diaphragmatic hernia (CDH), esophageal atresia, and urinary system disorder. Necrotizing enterocolitis (NEC) had the highest mortality rate. Using logistic regression, in-hospital death was predicted by extremely low birth weight (ELBW) (odds ratio (OR)=6.594; P=0.006), CDH (OR=13.954; P Conclusions This study describes CDH, NEC, and ELBW are independent predictive factors associated with in-hospital death of pediatric surgical patients in our NICU. Novel approaches for those conditions are required to improve the survival. Type of study Prognostic Levels of evidence II.

BACKGROUND The aim of the present study was to investigate the efficacy and safety of double-balloon enteroscopy (DBE) in postoperative pediatric patients. METHODS This was a retrospective analysis of pediatric patients 18 years and younger referred to Mie University Hospital. Twenty procedures in 11 children occurred postoperatively; 29 children (42 procedures) had not undergone surgery. RESULTS Among postoperative patients, five DBE procedures were performed via the oral route, 12 via the anal route, and three via a stomal route. Among nonoperative patients, 14 DBE procedures were performed via the oral route and 28 via the anal route. Four postoperative patients and two nonoperative patients had difficult pleating via the transanal route because of adhesions or thickening of the intestinal wall resulting from inflammation (P = 0.02). Excluding patients with stenosis, the mean length of endoscopic insertion for transanal procedures was significantly shorter among postoperative patients than among nonoperative patients (73.6 cm vs 160.5 cm, P

Personal service robots are rapidly entering our daily lives. It is indispensable to secure safety for the robots and it is an important research topic to avoid collision with persons especially for mobile robots. In this paper, we solve the problem by constructing a pedestrian model considering the existence of robots. In this model, we enhance Helbing's pedestrian model known as Social Force Model (SFM) by using the human-robot mutual estimation model of each other's intention, and we formulate the model in human-robot coexisting environment. By conducting simulation experiments, we show that safe and efficient mobile robot navigation can be done by using the proposed model.

Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by cutaneous and muscle manifestations. The association between DM and malignancy has been well recognized for many years. The clinical course of paraneoplastic DM may be affected by malignancies, although the cause and effect relationship between exacerbation of DM and cancer progression is uncertain. Herein, we report a 44-year-old woman who presented with progressive DM associated with rectal cancer. After curative resection of rectal cancer, DM symptoms resolved. Three months after surgery, blood test surveillance showed elevation of serum carcinoembryonic antigen levels, although the patient remained asymptomatic. One month later she had a DM flare-up, and multiple lung and liver metastases were found. She immediately underwent cancer chemotherapy with prednisolone therapy for DM. However, her condition deteriorated and she was unable to swallow. Percutaneous endoscopic gastrostomy was constructed, allowing alimentation and oral delivery, which made it possible to keep her on chemotherapy. She had remarkable response for unresectable metastases 8 weeks after the administration of chemotherapy. Seven months after onset of recurrence, her condition improved considerably and she had stable disease. Moreover, she can now eat food of soft consistency. Our case provides further support for the clinical importance of cancer chemotherapy for patients who have progressive DM and unresectable rectal cancer.

The aims of this study were to review our therapy and outcome for meconium peritonitis (MP) patients, and to clarify predictors of postoperative morbidity and mortality. We retrospectively reviewed a total 15 patients with MP who received surgical intervention at our institute from December 1990 to November 2012. Diagnosis of MP was confirmed by operative findings. We analyzed the relationship between outcome and patients' factors including patients' characteristics, prenatal diagnosis, type of MP, general condition, and surgical procedure. There was no relationship between outcome and the following factors: gender, gestational age, body weight at birth, delivery type, Apgar score, prenatal diagnosis, types and causes of MP, and surgical procedure. However, the preoperative presence of circulation deficiency and serum CRP values were statistically significant predictors of outcome in our MP patients. Prenatal diagnosis is essential for the first step of perinatal therapy for MP. Surgical strategy should be selected according to the information of prenatal diagnosis. Early surgical procedures to reduce systemic and abdominal inflammation just after birth may improve the outcome of severe MP cases.

Many children require emergency foreign body removal by bronchoscopy. Although a flexible bronchoscope is frequently used for removal of a bronchial foreign body in children, this procedure is difficult in children with a narrow tracheal lumen, even using a thin flexible bronchoscope. This report describes the use of a multiport airway adaptor to remove a bronchial foreign body with a flexible bronchoscope. The thicker forceps etc. were passed alongside the flexible bronchoscope through the adaptor. These findings suggest that this multiport airway adaptor will be useful as an advanced tool for foreign body removal in pediatric patients.

Anorectal malformation (ARM) is associated with a tethered spinal cord (TSC). Long-term functional outcome of untethering surgery for TSC in patients with ARM has not been well evaluated. Patients aged 7 years and older who underwent repair of ARM and spinal magnetic resonance imaging from January 1995 to December 2008 were reviewed retrospectively. Untethering surgery was performed in all patients who were diagnosed with TSC, regardless of the presence or of neurological symptoms. Clinical symptoms reflecting anorectal, urinary, and lower limb function were compared between patients complicated with TSC (TSC group, n = 17) and those without TSC (non-TSC group, n = 14). The median age at functional evaluation was 11.7 and 12.9 years in the TSC and non-TSC groups, respectively (p = 0.52). Untethering surgery for TSC was performed at a median age of 1.3 years. Preoperative urinary and lower limb dysfunction, except for vesicoureteral reflux in the TSC group in one patient, was improved after surgical detethering. Current anorectal function was comparable between the groups. Long-term functional outcome in patients with ARM and TSC undergoing untethering surgery is equivalent to that in those without TSC. Prophylactic surgical detethering for patients with ARM and TSC can be a treatment of choice to maximize neurological functional outcome.

SummaryA 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus.

Purpose This aim of the study is to determine whether the use of Seprafilm reduces the incidence and the medical costs of adhesive bowel obstruction (ABO) in children. Methods Pediatric patients undergoing laparotomy were prospectively assigned to the Seprafilm group, n = 441). A historical control group consisted of children without using Seprafilm (n = 409). The incidence of ABO during a 24-month follow-up period was compared between the groups. To clarify the cost–benefit relations, expenses for Seprafilm and medical costs for hospitalization related to ABO in the Seprafilm group were compared with the ABO-associated hospitalization costs in the control group. Results The cumulative incidence rate of ABO in the control group was significantly higher than in the Seprafilm group (4.9% vs. 2.0%, p = 0.015). Nearly all cases that required adhesiolysis had adhesions to areas other than the incision in both groups. In cost–benefit analysis, cost per patient was $105 higher in the control group than in the Seprafilm group, but this did not reach significance (p = 0.63). Conclusions Seprafilm reduces the incidence of ABO in the pediatric patients undergoing laparotomy. Although associated medical costs in the Seprafilm group were not significantly reduced, use of Seprafilm did not lead to an increase in cost. Wider range of Seprafilm application or an additional anti-adhesion device may help in preventing adhesion to areas other than the incision.

Dysregulation pattern of microRNA-7 (miR-7) and the clinical significance of its expression in colorectal cancer (CRC) are unresolved. Here, we investigated the relationship between clinicopathological factors, including prognostic outcome, and miR-7 expression in CRC tissues. We analyzed miR-7 expression levels by real-time reverse transcription polymerase chain reaction in 210 colorectal tissues (196 CRCs and 14 normal mucosae from healthy volunteers). miR-7 expression levels were significantly up-regulated in CRC tissues compared to normal colorectal mucosae. Elevated miR-7 expression was significantly correlated with tumour depth, venous invasion, lymphatic invasion, lymph node metastasis, and liver metastasis. High miR-7 expression was significantly associated with poor overall survival in patients with CRC (p=0.010). Moreover, miR-7 expression was an independent prognostic factor in patients with CRC (hazard ratio=1.854, 95% confidence interval=1.016-3.540; p=0.044). miR-7 acts as an oncogene in CRC and is significantly associated with tumour progression and poor prognosis.

Purpose: Intestinal dysfunction is a major problem after gastroschisis repair, and causes poor oral intake and poor body weight gain in infants with gastroschisis. Dai-kenchu-to (DKT) is often used in the treatment of gastrointestinal dysfunction in Japan. The purpose of this study was to analyze the effect of DKT on infants with uncomplicated gastroschisis. Methods: In this retrospective cohort study from 1991 to 2009, we assessed 16 infants with uncomplicated gastroschisis. Eight infants received 0.3 g/kg/day of DKT for 12 months (group 1) and 8 infants did not receive DKT (group 2). We analyzed their body weight as an indicator of the effect of DKT. Results: There were no significant differences in the background characteristics. The body weight of group 1 was significantly increased at the ages of 9 months (p = 0.0348) and 12 months (p = 0.0097), compared with group 2. Multivariate analyses revealed that only DKT administration had a significant impact on body weight gain at the ages of 9 months (p = 0.0201) and 12 months (p = 0.0111). No side effects related to DKT were reported. Conclusion: DKT administration might work safely and effectively for improving the body weight gain in infants with uncomplicated gastroschisis.

Enterostomy may lead to fluid and electrolyte imbalance, or impaired absorption of nutrition followed by impairment of growth. This study aimed to clarify the effectiveness of enteral refeeding (ER) in premature and full-term neonates.A retrospective database of all consecutive neonates who had enterostomy during 2000-2014 in a regional center was analyzed. Thirteen patients with ER (ER group) and 14 patients without ER (control group) were included. Detailed clinical data were evaluated with reference to the increment in body weight during ER.The ER group had a significantly higher rate in weight gain compared with the control group (P=0.0012), despite the gestational age (37weeks: P=0.0012, ≥37weeks: P=0.029). ER starting at a lower body weight was also associated with a higher weight gain (P=0.0002). Moreover, univariate and multivariate analyses showed that only the ER procedure (P0.0001) and birth weight (P=0.049) were significantly independent predictors of good weight gain.Using ER, low-birth-weight infants may have benefits, such as better acceleration of growth, than normal-birth-weight infants. We do not hesitate to perform ER, even in low-birth-weight neonates or those with low body weight, when starting ER.

Thoracoscopic repair is the preferred treatment for congenital diaphragmatic hernia (CDH); however, several complications, including visceral injury, hypercapnia, and a high incidence of recurrence, have been reported. The purpose of this study was to evaluate the efficacy of countermeasures against these complications at ensuring safe thoracoscopic repair. Between January 2000 and December 2014, 40 patients with Bochdalek-type CDH were treated. Of these, 24 patients met the defined criteria for this study, 8 of whom underwent thoracoscopic repair beginning in January 2010 (TS group) and 16 underwent laparotomy before December 2009 (LT group). Perioperative variables and postoperative complications were compared between the groups. Countermeasures against adverse events in the TS group included an endoscopic surgical spacer to prevent visceral injury, intrapulmonary percussive ventilation to avoid hypercapnia, pausing CO2 insufflation to reduce tension during the repair, and prioritizing patch repair in cases of strong tension at the defect. Primary closure was performed in 4 of 8 cases in the TS and 11 of 16 cases in the LT group. There was no visceral injury or conversion to laparotomy in the TS group. The mean operative duration was significantly longer (212 vs. 115 min, respectively, p = 0.0001), and the mean blood loss was significantly less in the TS than in the LT group (1.0 vs. 10.1 mL, respectively, p = 0.01). The intraoperative minimum arterial pH and maximum pCO2 were similar between the groups. All patients survived, and none experienced recurrence. Our countermeasures to complications of thoracoscopic repair may contribute to safe outcomes equivalent to those of laparotomy in patients meeting our criteria.

The 13-year-old boy underwent tumor enucleation for pancreatic head insulinoma close to the pancreatic main duct after a preoperative endoscopic pancreatic stent placed by endoscopic retrograde cholangiopancreatography. The tumor was safely excised by identifying the indwelled pancreatic stent during the surgical procedure without pancreatic duct injury or postoperative complications.

Background. Despite recent advances in surgical techniques and treatment options, gastric cancer (GC) remains the third most common cause of cancer-related deaths worldwide. Besides DNA sequence mutations, epigenetic alterations have emerged as significantly major players in cancer development. A-to-I RNA editing is a post-transcriptional modification that converts adenosines to inosines in both coding and noncoding RNA transcripts, and has recently been recognized has a novel epigenetic mechanism in GC pathogenesis. More specifically, A-to-I editing of AZIN1 transcripts was shown to be regulated by an adenosine deaminase acting on RNA-1 (ADAR1), and edited AZIN1 resulted in an aggressive phenotype during disease progression in some human cancers. The aim of this study was to clarify the clinical consequences of RNA editing status of AZIN1 and the RNA editing enzymes (ADAR1 and 2) in GC patients. Methods. Two hundred eighty-eight gastric specimens from one hundred forty-four patients who underwent surgery for GC were evaluated. We analyzed the RNA editing status of AZIN1 by RNA editing site-specific quantitative PCR (RESSqPCR). RESSqPCR allows quantitation of RNA editing levels using wild-type or edited AZIN1-specific primers, and RNA editing levels are calculated by determining the ratios of Ct values between edited vs. wild-type transcript expression levels. Furthermore, expression levels of ADAR1 and ADAR2 were evaluated by qPCR in GC tissues. Results. We observed a higher frequency of the AZIN1 RNA editing in tumors compared with normal mucosa in GC. RNA editing status of AZIN1 was significantly increased in a stage-dependent manner, and high frequency of RNA editing in AZIN1 significantly correlated with advanced T stage and presence of lymph node metastasis in GC patients. Multivariate analysis revealed that high frequency of RNA editing in the AZIN1 gene was an independent prognostic factor for poor disease free survival and overall survival. Furthermore, significant upregulation of ADAR1 and downregulation of ADAR2 was also observed in GC tissues compared with matched normal mucosa, and these alterations also significantly correlated with disease progression factors and poor prognosis in GC patients. Interestingly, ADAR1 expression level was positively correlated with RNA editing status of AZIN1 in GC tissues. Conclusions. Our findings revealed that altered gene-specific A-to-I editing events mediated by ADAR1 promote disease progression in GC. We conclude that assessment of RNA editing status of the AZIN1 gene might offer a novel and superior biomarker for a more accurate diagnosis of disease staging and may help predict clinical outcomes in GC patients. Citation Format: Yoshinaga Okugawa, Yuji Toiyama, Kunitoshi Shigeyasu, Takashi Ichikawa, Satoshi Oki, Koichiro Mori, Yuka Nagano, Hiromi Yasuda, Shigeyuki Yoshiyama, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Toshimitsu Araki, Yasuhiko Mohri, Motoyoshi Tanaka, Chikao Miki, Ajay Goel, Masato Kusunoki. Novel findings for the clinical significance of RNA editing status of AZIN1 and ADAR 1 and 2 expression levels in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4720. doi:10.1158/1538-7445.AM2017-4720

546 Background: Accumulating evidences reveal that overexpression of Heat shock protein 47 (HSP47) increase cancer progression, and that HSP47 expression in the tumor-associated stroma serve as diagnostic marker in various cancers. In addition, we recently performed immunohistochemistry to evaluate HSP47 expression in surgical colorectal cancer (CRC) specimens, and showed that the count of HSP47 positive spindle cell in cancer stroma was significantly associated with lymph node (LN) metastasis, early recurrence and poor prognosis in CRC patients. Thus, evaluating HSP47 expression in CRCs preoperatively may be valuable for planning the treatment of patients with CRC. In this study, we quantified the messenger RNA(mRNA) expression of HSP47 in CRCs by using preoperative biopsy samples, and analyzed the association between HSP47 mRNA expression and clinico-pathological factors including prognosis in patients with CRC. Methods: A total of 139 CRC samples, which were taken by biopsy before surgery at Mie University Hospital from 2000 to 2005, were enrolled. HSP47 gene expression was determined by quantitative real-time reverse transcription–PCR using Power SYBR Green PCR methods. Results: All CRC patients were classified according to the tumor-node-metastasis (TNM) classification system as follows: stage I (n = 33); stage II (n = 44); stage III (n = 33), and stage IV (n = 29). High HSP47 expression in CRC was significantly associated with higher T stage (p = 0.0163), LN metastasis (p = 0.0186), vessel invasion (p = 0.0328) and higher TNM staging (p = 0.0115). Kaplan-Meier analysis showed that patients with high HSP47 expression had significantly poorer overall survival (OS) than those with low (p = 0.0003). Furthermore, multivariate analyses revealed that HSP47 expression was an independent predictive marker for LN metastasis and poor OS in CRC patients, respectively (LN metastasis; OR; 2.3946, p = 0.0249, OS; HR; 2.7407, p = 0.00224). Conclusions: In conclusion, quantification of HSP47 expression using biopsy samples can identify the CRC patients who may suffer from LN metastasis and poor prognosis, preoperatively.

Background: MicroRNA (miRNA)-1290 is known to activate Wnt signaling pathway and increase the reprogramming-related transcript factors c-Myc and Nanog. Additionally, miR-1290 promotes the epithelial-mesenchymal transition and interferes with cellular differentiation. Previous report demonstrated that overexpressing miR-1290 shows extensive atrophy and intestinal metaplasia of the gastric mucosa, indicating that miR-1290 is involved in the precancerous lesions of the gastric epithelial cells. However, to the best of our knowledge, miR-1290 expression pattern, its clinical significance and molecular mechanism in colorectal cancer (CRC) have not been investigated. Materials and Methods: We screened miR-1290 expression in a subset of 36 tissue samples from normal colonic mucosa (n = 12), adenoma (n = 12) and CRC (n = 12). Next, we further validated miR-1290 expression in a larger, independent cohort, which included normal colonic mucosa (n = 21), adenoma (n = 26) and CRC (n = 179), and investigated the clinical significance of miR-1290 in CRC. In addition, CRC cell lines were transfected with anti-miR against miR-1290 for the assessment of its function. Results: In screening step, miR-1290 expression stepwise increased according to adenoma-carcinoma sequence, and its expression in adenoma and CRC was significantly higher than that in normal colonic mucosa, respectively (adenoma: p40mm), high grade of T stage (T3/4), lymphatic and venous invasion positive, lymph node metastasis and liver metastasis. In addition, Kaplan-Meier survival curves revealed that the CRC patients with high miR-1290 expression were significantly poorer overall survival than that with low expression, respectively (p = 0.0082). Our in vitro study demonstrated that attenuated miR-1290 expression resulted in inhibition of proliferation, invasion and migration capacity of CRC cell lines. Conclusions: We, for the first time, demonstrated that miR-1290 in CRC acts as onco-miRNAs that is supported by several evidences from our in vitro analysis and clinical data. MiR-1290 is significantly associated with malignant potential of CRC and can be the biomarker for predicting poor prognosis in patients with CRC. Citation Format: Yuka Nagano, Yuji Toiyama, Hiroki Imaoka, Hiroyuki Fujikawa, Junichiro Hiro, Susumu Saigusa, Minako Kobayashi, Toshimitsu Araki, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Kenichiro Ishii, Masato Kusunoki. MicroRNA-1290 promotes tumor progression and acts as a novel biomarker for poor prognosis in human colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1967.

14 Background: Although Gastric cancer (GC) mortality has been reduced by advances in new treatments and in chemotherapy, it still has a poor prognosis and high mortality. One of the reasons for poor prognosis is that at the time of diagnosis advanced GC with metastatic disease is often detected and it is frequently accompanied by peritoneal metastasis. Imaging studies are frequently used to predict peritoneal metastasis, however, these modalities did not obtain consistently high sensitivity and specificity in assessing peritoneal metastasis. Therefore, we investigated whether the combination of several serum markers and clinical factors could be used for preoperative prediction of peritoneal metastasis in GC as an indicator for neoadjuvant treatment. Methods: A total of 493 patients with GC were enrolled in our Hospital. Preoperative serum tumor markers [carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9], systemic inflammatory marker C-reactive protein (CRP), host immune markers [neutrophil and lymphocyte counts and their ratio (NLR)], albumin as a nutritional marker, and objective preoperative clinical factors were available as indicators of postoperative peritoneal metastasis. Results: This study included a total of 344 men and 149 women who were classified according to UICC TNM Classification: 264 patients had stage I disease, 79 stage II, 78 stage III and 72 stage IV. Specific clinical factors, including tumor size, histopathology of biopsy sample, and tumor morphology, were significantly correlated with peritoneal metastasis. CA19-9, lymphocyte count and NLR were also predictive factors for peritoneal metastasis. Multivariate analysis identified the clinical factors tumor morphology and histopathology, and laboratory markers CA19-9 and lymphocyte count as independent factors predictive for peritoneal metastasis. Next, a combination of independent predictive factors achieved high predictive accuracy (0.882) for peritoneal metastasis preoperatively. Conclusions: A combination of preoperative tumor features and serum parameters is an alternative method to preoperatively discriminate patients with GC with peritoneal metastasis from those without.

Tenascin-C (TN-C) is an extracellular matrix glycoprotein with high bioactivity. It is expressed at low levels in normal adult heart, but upregulated under pathological conditions, such as myocardial infarction (MI). Recently, we (Ref. 34 ) reported that MI patients with high serum levels of TN-C have a greater incidence of maladaptive cardiac remodeling and a worse prognosis. We hypothesized that TN-C may aggravate left ventricular remodeling. To examine the effects of TN-C, MI was induced by ligating coronary arteries of TN-C knockout (KO) mice under anesthesia and comparing them with sibling wild-type (WT) mice. In WT+MI mice, TN-C expression was upregulated at day 1, peaked at day 5, downregulated and disappeared by day 28, and the molecule was localized in the border zone between intact myocardium and infarct lesions. The morphometrically determined infarct size and survival rate on day 28 were comparable between the WT+MI and KO+MI groups. Echocardiography and hemodynamic analyses demonstrated left ventricular end-diastolic diameter, myocardial stiffness, and left ventricular end-diastolic pressure to be significantly increased in both WT+MI and KO+MI mice compared with sham-operated mice. However, end-diastolic pressure and dimension and myocardial stiffness of KO+MI were lower than those of the WT+MI mice. Histological examination revealed normal tissue healing, but interstitial fibrosis in the residual myocardium in peri-infarcted areas was significantly less pronounced in KO+MI mice than in WT+MI mice. TN-C may thus accelerate adverse ventricular remodeling, cardiac failure, and fibrosis in the residual myocardium after MI.

Paraquat causes lung injury by oxidative stress. After 48 h of intraperitoneal administration of paraquat (50 mg/kg of body weight) to rats, the vitamin C concentration in the lungs was significantly decreased, while lung vitamin E content was increased after 12 h. These results indicate that vitamin C directly reflected the oxidative stress in the lungs.