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Background/aim Inflammasomes are multiprotein complexes that evoke key inflammatory cascades. The present study evaluated the influence of inflammasome component expression in non-tumorous tissue on postsurgical hepatocellular carcinoma (HCC) prognosis. Materials and methods The expressions of candidate genes were investigated using real-time quantitative reverse-transcription polymerase chain reaction in resected HCC cases. In order to identify potential prognostic factors, statistical analyses were performed for each gene. Results The expression of nod-like receptor family, pyrin domain containing 3 (NLRP3), nod-like receptor family, CARD domain containing 4 (NLRC4), and absent in melanoma 2 (AIM2) was significantly higher in corresponding normal tissue (CN) compared to those in HCC. High expression of NLRP3, NLRC4, and caspase 1 (CASP1) in CN was significantly correlated with worse overall survival. Furthermore, multivariate analysis revealed that NLRP3 expression in CN greater than the median was an independent prognostic factor for poorer overall survival. Conclusion High expression of NLRP3, NLRC4, and CASP1 in background non-tumorous liver is significantly correlated with poor prognosis of patients after resection of HCC.

Objectives To investigate the impact of the body composition such as skeletal muscle, visceral fat and body mass index (BMI) on patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods A total of 265 patients who underwent curative surgery for PDAC were examined in this study. The total skeletal muscle and fat tissue areas were evaluated in a single image obtained at the third lumber vertebra during a preoperative computed tomography (CT) scan. The patients were assigned to either the sarcopenia or non-sarcopenia group based on their skeletal muscle index (SMI) and classified into high visceral fat area (H-VFA) or low VFA (L-VFA) groups. The association of clinicopathological features and prognosis with the body composition were statistically analyzed. Results There were 170 patients (64.2%) with sarcopenia. The median survival time (MST) was 23.7 months for sarcopenia patients and 25.8 months for patients without sarcopenia. The MST was 24.4 months for H-VFA patients and 25.8 months for L-VFA patients. However, sarcopenia patients with BMI ≥22 exhibited significantly poorer survival than patients without sarcopenia (MST: 19.2 vs. 35.4 months, P = 0.025). There was a significant difference between patients with and without sarcopenia who did not receive chemotherapy (5-year survival rate: 0% vs. 68.3%, P = 0.003). The multivariate analysis revealed that tumor size, positive dissected peripancreatic tissue margin, and sarcopenia were independent prognostic factors. Conclusions Sarcopenia is an independent prognostic factor in PDAC patients with a BMI ≥22. Therefore, evaluating skeletal muscle mass may be a simple and useful approach for predicting patient prognosis.

The administration of fluid irradiated with non-equilibrium atmospheric pressure plasma (NEAPP) has attracted much interest as a novel therapeutic method for cancer. The authors previously reported on the efficacy of plasma-activated medium (PAM) for treating cancer cell lines through the induction of apoptosis. In this study, the therapeutic effect of PAM was evaluated in vivo using a peritoneal metastasis mouse model. Two gastric cancer cell lines were used in proliferation assays performed to optimize the production of PAM by changing the distance between the plasma source and the medium surface and by altering the volume of irradiated medium. Wound-healing and adhesion assays were conducted to determine the effect of PAM therapy on cell migration and adhesion capacity in vitro. Finally, a mouse model established by the intraperitoneal injection of enhanced green fluorescent protein-tagged gastric cancer cells was used to explore the efficacy of PAM administered intraperitoneally in inhibiting peritoneal metastasis formation. Shorter distances between the plasma source and the medium surface and smaller volumes of treated medium increased the anti-tumor effect of PAM. The PAM treatment attenuated gastric cancer cell migration and adhesion in vitro. The intraperitoneal administration of PAM decreased the formation of peritoneal metastatic nodules by 60% in the mouse model, and no adverse events were observed. Plasma-activated liquids may represent a novel therapeutic method for the treatment of peritoneal metastases in gastric cancer.

Laparoscopy-assisted distal gastrectomy is one of the major treatments for early stage gastric cancer, particularly in the East Asia. In this method, extracorporeal anastomosis is performed via a small laparotomy wound, but excessive tissue traction may be encountered during the anastomotic procedure. Therefore, we developed an original procedure for extracorporeal Billroth-I reconstruction: end-to-end stapling gastroduodenostomy with complete double stapling technique. This procedure aims to reduce the problems related to maneuvers through a small laparotomy.An end-to-end anastomosis is constructed on the transection line using a circular stapler inserted from the distal end of the greater curvature of the remnant stomach. Short-term outcomes were reviewed in 218 consecutive patients who underwent complete double stapling technique reconstruction after laparoscopy-assisted distal gastrectomy between 2002 and 2012. Findings from GI endoscopy were reviewed in 110 patients.The mean operative time was 216 min, and mean blood loss was 163 mL. There was no conversion to the open surgery and no operative death. Eight patients (3.6%) had anastomosis-related postoperative complications. In follow-up endoscopic examinations 1 year after surgery, grade 3 or higher residual food was seen in 17.2% of patients. Gastritis extending to the entire remnant stomach was observed in 8.2% of patients, and grade 3 gastritis was seen in 2.7%. Los Angeles classification grade A or higher reflux esophagitis was found in 10.9%.Billroth-I reconstruction by the complete double stapling technique is a safe and feasible procedure. This method provides satisfactory short-term outcomes, including the incidence of reflex remnant gastritis and esophagitis.

Gastrectomy with systemic lymphadenectomy is the standard of care for resectable gastric cancer (GC), but it is sometimes associated with postoperative morbidity. Predicting complications is therefore an essential part of risk management in clinical practice. The renal function is routinely evaluated before surgery by blood examinations to determine dose of medication and infusion. However, the value of various parameters of renal function in prediction of postoperative complications remain unclear. We included 315 patients who underwent curative D2 gastrectomy for clinical T2–T4 GC without preoperative treatment, and evaluated the correlation between the incidence of postoperative complications and the indicators of renal function. Forty-three patients experienced clinically relevant postoperative complications. Estimated glomerular filtration rate (eGFR) showed a higher area under the curve for predicting complications compared with urea nitrogen, creatinine, and creatinine clearance. The optimal eGFR cutoff value was 63.2 ml/min/1.73 m2, and eGFR

Evidence indicates that impaired immunocompetence and nutritional status adversely affect short-term and long-term outcomes of patients with cancer. We aimed to evaluate the clinical significance of preoperative immunocompetence and nutritional status according to Onodera's prognostic nutrition index (PNI) among patients who underwent curative gastrectomy for gastric cancer (GC). This study included 260 patients with stage II/III GC who underwent R0 resection. The predictive values of preoperative nutritional status for postoperative outcome (morbidity and prognosis) were evaluated. Onodera's PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (per mm3). The mean preoperative PNI was 47.8. The area under the curve for predicting complications was greater for PNI compared with the serum albumin concentration or lymphocyte count. Multivariate analysis identified preoperative PNI < 47 as an independent predictor of postoperative morbidity. Moreover, patients in the PNI < 47 group experienced significantly shorter overall and disease-free survival compared with those in the PNI ≥ 47 group, notably because of a higher prevalence of hematogenous metastasis as the initial recurrence. Subgroup analysis according to disease stage and postoperative adjuvant treatment revealed that the prognostic significance of PNI was more apparent in patients with stage II GC and in those who received adjuvant chemotherapy. Preoperative PNI is easy and inexpensive to determine, and our findings indicate that PNI served as a significant predictor of postoperative morbidity, prognosis, and recurrence patterns of patients with stage II/III GC.

Since current digital fabrication relies on 3D printer very much, there are several concerns such as printing cost (i.e., both financial and temporal cost) and sometimes too homogeneous impression with plastic filament. To address and solve the problem, we propose ReFabricator, a computational fabrication tool integrating everyday objects into digital fabrication. ReFabrication is a concept of fabrication, mixing the idea of Reuse and Digital Fabrication, which aims to fabricate new functional shape with ready made products, effectively utilizing its behavior. As a system prototype, we have implemented a design tool which enables users to gather up every day objects and reassemble them to another functional shape with taking advantages of both analog and digital fabrication. In particular, the system calculates the optimized positional relationship among objects, and generates joint objects to bond the objects together in order to achieve a certain shape.

Identification of novel gastric cancer (GC)-related molecules is necessary to improve management of patients with GC in both diagnostic and therapeutic aspects. The aim of the present study was to determine whether protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in the progression of GC and whether it serves as a novel diagnostic marker and therapeutic target. We conducted global expression profiling of GC cell lines and RNA interference experiments to evaluate the effect of PRMT5 expression on the phenotype of GC cells. We analysed tissues of 179 patients with GC to assess the association of PRMT5 mRNA levels with clinicopathological factors. Differential expression of PRMT5 mRNA by GC cell lines correlated positively with the levels of GEMIN2, STAT3 and TGFB3. PRMT5 knockdown reduced the proliferation, invasion and migration of a GC cell line. PRMT5 mRNA levels were significantly higher in GC tissues than the corresponding adjacent normal tissues and were independent of tumour depth, differentiation and lymph node metastasis. High PRMT5 expression was an independent risk factor of positive peritoneal lavage cytology (odds ratio 3.90, P=0.003) and decreased survival. PRMT5 enhances the malignant phenotype of GC cell lines and its expression in gastric tissues may serve as a biomarker for patient stratification and a potential target of therapy.

In our department, we have attempted to reduce the incidence of complications of conventional esophagectomy. The objective of this retrospective study was to report the short-term outcomes of esophagectomy. We reviewed 138 consecutive patients who had undergone subtotal esophagectomy by combined laparotomy via a 12-cm upper abdominal vertical incision combined with right anterior muscle-sparing thoracotomy from August 2010 to August 2014. Most of the cervical para-esophageal lymph node dissection was completed within the thoracic cavity. We performed three-field dissection in patients with tumors in the upper or middle third of the esophagus with clinical lymph node metastases in the superior mediastinum; the others underwent two-field dissection. We performed neck anastomoses in patients undergoing three-field dissection and thoracic anastomoses in those undergoing two-field dissection. Effective postoperative pain management was achieved with a combination of epidural anesthesia and paravertebral block. Postoperative rehabilitation was instituted for early ambulation and recovery. Enteral nutrition via a duodenal feeding tube was administered from postoperative day 2. Median hospital stay after surgery was 15 days (range, 10–129). Rates for both 30-day and in-hospital mortality were 0%. Morbidity rate for all Clavien–Dindo grades was 41.3%, whereas the morbidity rate for Clavien–Dindo grades III and IV was 7.2%. Anastomotic leakage developed in two patients (1.4%), recurrent laryngeal nerve palsy in 11 (8.0%), and pneumonia in nine (6.5%). Good short-term outcomes, especially regarding anastomotic leaks, were achieved by consistent improvements in surgical techniques, optimization of several operative procedures, and appropriate perioperative management.

Identification of novel molecules implicated in the malignancy of gastric cancer (GC) is key to the development of personalized treatments and the improvement of patient outcome. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE) regulates apoptosis and metastasis via interactions with various genes. This study aimed to evaluate the function and clinical significance of NRAGE in GC. The expression of NRAGE and its putative interacting genes apoptosis antagonizing transcription factor (AATF), p75 neurotrophin receptor (p75NTR), and proliferating cell nuclear antigen (PCNA) were determined in GC cell lines using reverse transcription-polymerase chain reaction (RT-PCR). The effect of NRAGE knockdown by small interfering RNA (siRNA) on GC cell behavior also was evaluated. In addition, NRAGE expression was determined in 179 pairs of resected gastric tissues. Expression of NRAGE mRNA positively correlated with that of AATF, and NRAGE knockdown significantly decreased the proliferation, migration, and invasion of GC cells. The mean level of NRAGE mRNA expression was significantly higher in GC tissues than in corresponding adjacent normal tissues. The expression patterns of NRAGE mRNA and protein were closely correlated. A stepwise elevation in NRAGE mRNA expression in GC tissues was observed with increasing Union for International Cancer Control (UICC) stage. High NRAGE expression in GCs was associated with shortened recurrence-free survival and identified as an independent prognostic factor (hazard ratio, 1.83; 95 % CI, 1.12–3.02, p = 0.017). The results indicate that NRAGE represents a putative oncogene associated with a malignant phenotype of GC. In GC, NRAGE may serve as a predictive biomarker and a target of molecular therapy.

Skeletal muscle depletion predicts poor prognosis of patients with certain cancers. However, the correlation between low skeletal muscle index (SMI) and the prognosis of hepatocellular carcinoma (HCC) is not well understood.To determine their influence on prognosis, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the level of the third lumbar vertebra of 195 patients who underwent primary hepatectomy for hepatocellular carcinoma (HCC). We defined sarcopenia using cutoff values for SMI as 43.75 cm(2)/m(2) and 41.10 cm(2)/m(2) for males and females, respectively.Sarcopenia was present in 89 of 195 (45.6%) patients and correlated significantly (P 0.001) with female sex, low body mass index (BMI), low subcutaneous fat area, low VFA, and low serum albumin levels. There was a trend indicating the association of sarcopenia with poor cumulative recurrence rate (CRR) (P = 0.13). In patients with BMI ≥22, CRR was significantly different between patients with or without sarcopenia (19.0 or 35.2 months, respectively, P = 0.03). In contrast, there was no significant difference in patients with BMI ≥22 as a function of VFA (P = 0.47). When the cohort was limited to patients with BMI ≥22, multivariate analysis showed that sarcopenia was a significant independent risk factor for recurrence (hazard ratio = 1.6; 95% confidence interval, 1.1-2.5; P = 0.02).Low-SMI was an independent adverse prognostic factor for CRR in patients with BMI ≥22. Therefore, preventing muscle wasting may improve the CRR of patients with HCC.

Hepatocellular carcinoma (HCC) is a fatal disease, primarily due to the limited effective therapies available for patients with advanced or recurrent stages of the disease. Therefore, in order to improve patient prognosis, it is important to identify an informative biomarker for HCC progression, as well as a molecular target for therapy. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE), a member of the type II melanoma-associated antigen family, mediates apoptosis and cell death through interactions with a wide range of proteins, and is implicated as a tumor suppressor or oncoprotein depending on cell type. However, the role of NRAGE in HCC is currently unknown, therefore, the present study aimed to identify the underlying function of NRAGE in HCC tumorigenesis. Resected tumor and non-cancerous liver tissues from 151 patients with HCC, alongside HCC cell lines, were analyzed by polymerase chain reaction and immunohistochemical techniques to determine NRAGE expression levels, as well as the expression levels of potential genes encoding interacting proteins. It was demonstrated that the expression levels of NRAGE mRNA correlated significantly with those of apoptosis-antagonizing transcription factor (AATF), and were not affected by cirrhosis in non-cancerous liver tissues when compared to elevated levels in HCC tissues. The expression patterns of NRAGE protein and mRNA were consistent among 30 representative specimen pairs. Furthermore, increased NRAGE expression in patients with HCC correlated significantly with a shorter disease-specific survival time, and was identified as an independent prognostic factor via multivariate analysis (hazard ratio, 2.23; 95% confidence interval, 1.06-3.83; P=0.020). Therefore, the results of the present study indicated that increased NRAGE expression affects HCC progression via its interaction with AATF, and may represent a novel biomarker and molecular target for the treatment of HCC.

Shigeki Nakagawa, Lan Wei and Won MinSong are co-first author.; International audience; Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention.

Pancreaticoduodenectomy is performed for pancreatic head cancer that originated from the dorsal or ventral primordium. Although the extent of lymph node (LN) dissection is the same irrespective of the origin, the lymphatic continuities may differ between the 2 primordia.Between March 2003 and September 2010, 152 patients underwent pancreaticoduodenectomy for pancreatic cancer. One hundred six patients were assigned into 2 groups according to tumor location on preoperative computed tomography, and their clinical and pathological features were retrospectively analyzed in view of the embryonic development of the pancreas.Sixty of 106 patients were classified with tumors that were derived from the dorsal pancreas (D group) and 46 from the ventral pancreas (V group). The frequency of LN involvement around the middle colic artery (LN 15) in the D group was higher than in the V group (P = 0.008). The rate of additional resection of the pancreas tended to be higher in the D group (P = 0.067).The present study showed the detailed pattern of spread of pancreatic ductal carcinoma to the LNs and provided important information for determining the optimal surgical strategy.

Background After pancreatoduodenectomy in patients with celiac axis stenosis or obstruction, it becomes problematic to maintain the upper abdominal organ blood flow, especially to the liver. The aim of this study was to investigate the celiac axis stenosis caused by median arcuate ligament (MAL) compression and to classify it according to preoperative image findings. Methods From January 1989 to November 2010, 562 patients underwent operations for diseases of the pancreatic head region in our department. To diagnose celiac artery compression by the MAL, angiography was used in the early period and 3-dimensional image reconstruction of multidetector-row computed tomography was used from 2004. The morphologic characteristics of the celiac axis stenosis were analyzed during intraoperative treatment. Results Twelve (2.1%) patients were diagnosed with MAL compression, and 8 of these patients only underwent MAL division to restore the celiac artery blood flow. One patient required conservation of the collateral circulation, and 2 patients needed arterial reconstruction. In the analysis of the level of origin of the celiac axis, there were no remarkable differences between nonstenotic and stenotic cases, or between mild and severe stenotic cases. Morphologic grades were defined based on the preoperative image findings and consequent intraoperative treatments. Conclusion Preoperative grading of celiac axis stenosis could make pancreatoduodenectomy safer with maintenance of the upper abdominal organ blood flow in patients with MAL compression.

Although several studies have reported that locally administering oncolytic viruses effectively targets malignancies, the efficacy of systemically administered oncolytic viruses is restricted. Recently, however, it was reported that systemic administration of oncolytic vesicular stomatitis virus adsorbed onto antigen-specific lymphocytes was effective against malignancies. We hypothesized that intravenously administering such virus might have significant potential in treatment of the malignant tumors. We adsorbed oncolytic herpes simplex virus-1 mutant R3616 onto lymphocytes harvested from mice with acquired antitumor immunity. We administered adsorbed R3616 to peritoneally disseminated tumors and analyzed the efficacy of this treatment. Mice administered adsorbed R3616 survived significantly longer than mice administered R3616 adsorbed onto non-specific lymphocytes, or mice administered either virus or tumor antigen-specific lymphocytes alone. In this context, herpes oncolytic virus is a promising treatment not only for primary lesions, but also for multiple metastasizing lesions. This treatment strategy may become one of the most effective methods for systemic virus delivery.

砂と含水比の異なる自然粘土を様々な割合で混合した土に対し，一連のベンダーエレメント試験を行った．その結果，細粒分含有率が低く，砂が骨格構造を形成する領域と粘土が構造の主体となる領域の境界は，粘土の含水比により異なることが明らかとなった．初期せん断弾性係数と間隙比の関係は，細粒分含有率によって異なるが，細粒分を粗粒分と等価とみなす割合である寄与率bの概念を導入した等価骨格間隙比を用いることにより，初期せん断弾性係数と等価骨格間隙比との間に一義的対応関係が存在することが明らかとなった．また，等価骨格間隙比，拘束圧の関数として混合土のせん断弾性係数の評価式を提案した．

A retrospective study was performed to clarify the correlation between radiographic type of portal vein (PV) invasion and pathological grade of PV wall invasion, and their correlation with postoperative prognosis.In many patients with pancreatic cancer, PV resection is necessary to increase resectability and obtain cancer-free margins.We analyzed 671 patients who had undergone surgery for invasive adenocarcinoma of the pancreas between July 1981 and June 2010. Radiographic types of PV invasion of pancreatic head cancer were classified into A (normal), B (unilateral narrowing), C (bilateral narrowing), or D (complete obstruction with collateral veins), by portography or computed tomography. Pathological grades of PV wall invasion were classified as 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima).Four hundred and sixty-three patients underwent resection, and PV resection was performed in 297. Combined arterial vessel resection was performed in 16 cases. No significant difference in operative mortality was observed between PV preservation (0.6%) and PV-only resection (2.1%), and no operative deaths occurred after 1999. Radiographic classification of PV invasion correlated with incidence of pathological PV wall invasion. In pancreatic head carcinoma, no pathological PV wall invasion was observed in type A (n = 111). Pathological PV invasion was observed in 51% of type B (42/82), 74% of type C (72/97), and 93% of type D (63/68). Long-term survival (5 years) was observed in types A and B, and grades 0 and 1 subgroups.Pancreatectomy with PV resection can be performed safely. Even in radiographic classification type B, pathological PV wall invasion was observed in 51% of patients. Long-term survival was observed in types A and B, and grades 0 and 1.

Background Hepatocellular carcinoma (HCC) is a major health problem, and identification of new tumor-related genes is an urgent task. Methods To detect tumor-related genes effectively, we performed double-combination array analysis, which consisted of an expression array and a single nucleotide polymorphism (SNP) array of a single surgical HCC specimen. Results Expression array analysis identified AKAP12 as one of the genes with reduced expression in HCC tissues when compared with non-cancerous adjacent hepatic tissues. In addition, AKAP12 expression levels in tumor tissues from 48 HCC samples were significantly lower (P

Pylorus-preserving pancreatoduodenectomy (PPPD) has replaced conventional pancreatoduodenectomy with a distal gastrectomy (cPD) as the most commonly performed procedure. However, there has been no evidence from prospective studies to indicate the overwhelming superiority of PPPD over cPD. A recent report revealed that resection of the pyloric ring reduced the incidence of delayed gastric emptying (DGE) in a randomized controlled trial. In 158 patients with pancreatic head cancer, the perioperative outcomes and long-term nutritional consequences were retrospectively compared among three types of pancreatoduodenectomy: cPD; PPPD; and subtotal stomach-preserving pancreatoduodenectomy (SSPPD), in which the pyloric ring and duodenum were removed and more than 90% of the stomach was preserved. The incidence of DGE was significantly higher in the PPPD group than in the cPD and SSPPD groups (27.3 vs. 5.8 and 5.4%, respectively; P = 0.0012). The serum albumin concentration and total lymphocyte count at 1 year postoperatively were significantly higher in the SSPPD group than in the PPPD group (P = 0.0303 and P = 0.0203, respectively). The patients in the SSPPD group showed longer survival times than the patients in the cPD and PPPD groups (median survival times, 21.3, 17.1, and 17.7 months, respectively), although the differences did not reach statistical significance. Our results suggest that preservation of the pyloric ring without vagal innervation has little significance, and that SSPPD with better perioperative and long-term outcomes is more suitable as a standard procedure for patients with pancreatic head cancer.

Background & Aims A single nucleotide polymorphism 61*G (rs4444903) in the epidermal growth factor ( EGF ) gene has been associated, in 2 case-control studies, with hepatocellular carcinoma (HCC). We tested associations between demographic, clinical, and genetic data and development of HCC, and developed a simple predictive model in a cohort of patients with chronic hepatitis C and advanced fibrosis. Methods Black and white subjects from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial (n = 816) were followed up prospectively for development of a definite or presumed case of HCC for a median time period of 6.1 years. We used the Cox proportional hazards regression model to determine the hazard ratio for risk of HCC and to develop prediction models. Results Subjects with EGF genotype G/G had a higher adjusted risk for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence interval, 1.05–4.23; P = .03). After adjusting for EGF genotype, blacks had no increased risk of HCC risk compared with whites. Higher serum levels of EGF were observed among subjects with at least one G allele ( P = .08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC. We developed a simple prediction model that included the EGF genotype to identify patients at low, intermediate, and high risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%, and 26%, respectively. Conclusions We associated the EGF genotype G/G with increased risk for HCC; differences in its frequency among black and white subjects might account for differences in HCC incidence between these groups. We developed a model that incorporates EGF genotype and demographic and clinical variables to identify patients at low, intermediate, and high risk for HCC.

To assess the prognostic effect of intraoperative radiotherapy (IORT) in unresectable pancreatic cancer.We reviewed 198 patients with unresectable pancreatic cancer, which was found during experimental laparotomy. Liver metastasis was observed in 70 patients, peritoneal metastasis in 44, liver and peritoneal metastasis in 23 and locally advanced tumor in 61. Treatment consisted of IORT with or without postoperative chemotherapy. Overall survival (OS) and prognostic factors were evaluated for each pattern of disease spread.IORT was performed in 120 patients, and chemotherapy was administered in 80. Sixty patients did not receive either treatment. OS in the untreated group was significantly inferior to that for IORT alone and IORT plus gemcitabine (GEM)-based chemotherapy. IORT and GEM-based chemotherapy were identified as independent prognostic factors [hazard ratio (HR) = 0.51, p0.001; HR = 0.43, p0.001]. IORT was an independent prognostic determinant for patients with peritoneal metastasis (HR = 0.24, p = 0.011) but not for those with liver metastasis (HR = 0.78, p = 0.381).IORT followed by GEM-based chemotherapy is the recommended treatment strategy in unresectable pancreatic cancer. and IAP.

The 2007 Niigata-ken Chuetsu-oki (Off Mid-Niigata) earthquake caused the liquefaction of the sandy soil distributed near the coast of the Japan Sea in the middle of Niigata Prefecture. The liquefaction-induced damage occurring in many residential areas was investigated in detail by means of victim interviews, visual inspections, Swedish Weight Sounding tests, Standard Penetration Tests, old topographical map examinations, etc. Based on in situ soil investigations, the liquefied soil layers were estimated for each area. As a result, it was confirmed that the liquefied areas were mainly sand dune hinterlands, flood plains, reclaimed old river channels and sandy fills with high groundwater table. Among them, damage was especially serious on land having an inclined ground surface due to the flow of foundations, on the cut-fill borders of artificially developed land due to landslides and at the toes of sand dune slopes due to the thrust of the sliding soil and/or the collision of the sliding soil with objects. These investigation results also revealed that soil improvement by cement mixed columns is an effective countermeasure against liquefaction-induced damage unless lateral spreading of the subsoil arises.

細粒分含有率を調整したしらすの三軸供試体を用いてベンダーエレメント試験を実施し，せん断弾性係数を測定した．しらすは非結晶の火山ガラスを主成分とする脆弱な粒子から成り，細粒分を多く含むことが特徴である．実験より，しらすの細粒分に着目したせん断弾性係数の定式化を試みた．しらすのせん断弾性係数は細粒分含有率に依存し，間隙比や骨格間隙比との間に一義的関係を見出すことができなかった．そこで，細粒分を粗粒分と等価とみなす割合である寄与率bを考慮した等価骨格間隙比を導入することにより，せん断弾性係数の一義的な評価が可能となった．最終的に，細粒分含有率，等価骨格間隙比および拘束圧の関数形としたしらすのせん断弾性係数の定式化を行った．

Purpose: Oncolytic viral therapy is a newly developed modality to treat tumors. Many clinical trials worldwide have examined the efficacy of locally injected oncolytic viruses. However, systemic intravascular injections are limited by the humoral immune response, which dramatically decreases the level of infection. To overcome this limitation, we encapsulated the oncolytic virus in liposomes. Methods: The infectious properties of the herpes simplex virus type 1 (HSV-1) mutant, hrR3, with or without liposomes in the presence of neutralizing antibodies were evaluated using replication and cytotoxicity assays in vitro. To evaluate the efficacy of intravascular virus therapy with liposomes in the presence of neutralizing antibodies, immunized mice bearing multiple liver metastases were intraportally or peritoneally administered hrR3 or hrR3 complexed with liposomes. Results: Anti-HSV antibodies attenuated the infectiousness and cytotoxicity of hrR3, whereas hrR3/liposome complexes were not attenuated by these anti-HSV antibodies. Although the survival rate of non-immunized mice treated with hrR3 alone was similar to that of mice treated with the hrR3/liposome complexes, the survival rates of immunized mice treated with hrR3 alone were significantly reduced compared to mice treated with the hrR3/liposome complexes. Conclusions: This systemic intravascular delivery of hrR3/liposome complexes in the presence of pre-existing neutralizing antibodies is effective to treat multiple liver metastases.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.

Background: Pancreatic cancer is one of the incurable cancers among solid malignancies. Basically, R0 tumor resection could be one of the critical factors for their prognosis. However, pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage and skipped lesion like tumor budding. We applied our ‘molecular surgical margin analysis' using tissue imprinting procedure to evaluate the precise surgical margin status of the surgical specimens after pancreatoduodenectomy. Methods: Quantitative methylation specific PCR (QMSP) assay for 3 representative tumor-specific methylation markers (CD1D, KCNK12, PAX5) were established and validated by paired normal and tumor tissues from pancreatic ductal carcinoma cases (n=48). Then, these markers were applied to prospectively collected peritoneal lavage samples (n=16), drainage fluid samples (n=18) and surgical margin imprinting samples (n=11). Results: QMSP values of tumor tissues were significantly higher than adjacent normal tissues and relatively high specificity to cancer cells in all three markers with optimal cut-off values (CD1D: P Conclusion: Very cancer-specific methylation detection assay was established. Although we still need to follow-up the cases for a year or more, invisible cancer cells in the fluid or on the surgical margin might have an association with tumor recurrence after the surgery. Citation Format: Masamichi Hayashi, Suguru Yamada, Hiroshi Tanabe, Yoshiyasu Kato, Katsuhito Tanaka, MItsuru Tashiro, Haruyoshi Tanaka, Tomonari Asano, Hideki Takami, Masaya Suenaga, Yukiko Niwa, Yasuhiro Kodera. Molecular surgical margin analysis of pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3330.

A retrospective study was performed to determine the prognostic implications of invasion to the splenic vessels in pancreatic body and tail cancer.Involvement of the splenic artery (SA) and vein (SV) is frequently observed in carcinoma of the body and tail of the pancreas, but its correlation with various other clinicopathologic factors and prognosis has not been explored in detail.Fifty-one patients who had undergone distal pancreatectomy for invasive adenocarcinoma of the body and tail of the pancreas were discreetly selected from the prospective data base for analyses. Cases that required extended surgery due to invasion of the major vessels such as the portal vein, common hepatic artery, celiac artery, and superior mesenteric artery were excluded. Correlation between invasion of the splenic vessels and prognosis and other clinicopathologic factors were analyzed.Seventeen patients with invasion of the SA had a significantly inferior prognosis compared with those without the invasion (P = 0.0067), whereas invasion of the SV, observed in 24 patients, did not affect prognosis. Additionally, invasion of the SA significantly correlated with tumor sizeor = 2 cm, anterior serosal infiltration, perineural invasion and SV invasion (P = 0.0440, P = 0.0406, P = 0.0460, and P = 0.0173, respectively). In univariate analysis, SA invasion, lymph node metastasis, and anterior serosal infiltration were identified as significant poor prognostic factors. In multivariable analysis, only SA invasion was an independent prognostic factor (odds ratio, 2.611, P = 0.0196).Our results indicated that the invasion of the SA, but not that of the SV, is a crucial prognostic factor in pancreatic body and tail cancer.

53 Background: Hepatic metastasis of gastric cancer has become a growing issue, because effective treatment and specific biomarkers are not available. The aim of this study was to identify a molecule mediating hepatic metastasis, which serves as a diagnostic marker, and to determine its potential as a therapeutic target. Methods: Stable knockdown gastric cancer cells were established using genome editing technique and cell activities were compared to control cells in vitro and in vivo. Tissue expression levels of the candidate molecule were evaluated in 300 patients with gastric cancer and correlated to clinicopathological parameters including patterns of metastasis and recurrences. Results: Global expression analysis revealed that synaptotagmin VII (SYT7) was overexpressed in gastric cancer tissues with hepatic metastasis. Gastric cancer cell lines differentially expressed high levels of SYT7 that positively correlated with those of SNAI1 and TGFB3, and inversely with RGS2. Stable knockout of SYT7 inhibited the proliferation of gastric cancer cells, indicated by increased apoptosis, and decreased cell migration, invasion, and adhesion abilities. The tumorigenicity of SYT7 knockout cells was moderately reduced in a mouse subcutaneous model and more strikingly decreased in a hepatic metastasis model. The protein expression levels of BCL2 and HIF1A were decreased in tumors formed by SYT7 knockout cells, and SYT7 levels in primary gastric cancer tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. Conclusions: SYT7 serves as a target for treating hepatic metastasis of gastric cancer as well as a diagnostic tool.

416 Background: Several studies have shown that nutritional support is important to reduce chemotherapy-related toxicities and improve tolerance to chemotherapy, but little is known about the nutritional influence of neoadjuvant therapy (NAT) for pancreatic cancer. The aim of this study was to assess the influence of NAT on nutritional status and the effectiveness of postoperative nutritional support in patients with NAT for pancreatic cancer. Methods: Between 2010 and 2017, 169 consecutive patients who underwent pancreatoduodenectomy of pancreatic cancer were enrolled, and divided into the neoadjuvant group (NAG, n = 70) and the control group (CG, n = 99). We assessed the change of nutritional index (body weight, albumin and rapid turnover proteins; retinol binding protein, prealbumin and transferrin), inflammatory index, and inflammation-based prognostic scores during NAT. Perioperative change of rapid turnover proteins at the point of pre-operation, postoperative day (POD) 5, POD12 and POD21, and perioperative and oncological outcomes between NAG and CG were evaluated. Finally, we divided NAG into nutrition group (n = 27) who received postoperative enteral immunonutrition from POD 1 to POD 21 and without nutrition group (n = 41), and compared perioperative change of rapid turnover proteins between two groups. Results: After NAT, the retinol binding protein, prealbumin, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and prognostic nutrition index significantly got worse in NAG (P < 0.05). The recovery of rapid turnover proteins after POD5 was significantly worse in NAG compared to CG (P < 0.05). There was no significant difference in the incidence of postoperative complications and time to adjuvant therapy between two groups. The recovery of retinol binding protein and prealbumin after POD12 was significantly better in nutrition group compared to without nutrition group (P < 0.05). Conclusions: NAT for pancreatic cancer could decrease nutritional status and its postoperative recovery. Postoperative enteral nutrition could be effective in patients with NAT for pancreatic cancer. Based on these results, we plan to perform the nutritional support at earlier stage of therapy.

523 Background: Gemcitabine plus nab-paclitaxel (GnP) treatment is recommended for metastatic pancreatic adenocarcinoma (PDAC), and has been widely spread in our clinics. However, the usefulness for the patients with locally advanced PDAC is still controversial. We designed the phase I study to assess the toxicity and decide the recommended dose based on dose-limiting toxicity (DLT) of concurrent chemoradiotherapy using GnP for unresectable locally advanced (UR-LA) PDAC. Methods: UR-LA PDAC patients were enrolled in this clinical trial. The patients received the GnP on days 1, 8 and 15 every 28 days, and the cycles were repeated until PD. The patients were scheduled to receive gemcitabine (mg/m2) and nab-paclitaxel (mg/m2) at 5 dose levels: 400/75 (level 0), 600/75 (level 1), 600/100 (level 2), 800/100 (level 3) and 800/125 (level 4). Radiation therapy was delivered as a total dose of 50.4 Gy in 28 fractions, 1.8Gy per day. DLT was defined as grade 4 leucopenia or neutropenia ≥ 3 days, grade 3 neutropenia with fever ≥ 38℃, grade 3 or 4 thrombopenia, grade 3 non-hematological toxicity and > 14 days delay of treatment. Response and disease control rate, safety, adverse events, PFS and OS were evaluated. Results: Twelve patients were enrolled in this study. Treatment was well tolerated, and every 12 patients completed radiotherapy of 50.4 Gy. Our recommended dose was level 3, gemcitabine 800 mg/m2 and nab-paclitaxel 100 mg/m2. One patient experienced the DLT. The response rate was 41.7% and disease control rate was 75% (PR: 5, SD: 4, PD: 3). Median OS was 9.0 months. Among 12 patients, 6 (50%) patients underwent conversion surgery, and the pathological CR was observed in 2 patients. Conclusions: The concurrent chemoradiotherapy using GnP for UR-LA PDAC can be delivered safely and the high rate of conversion surgery was observed in our clinical trial. Based on this results, we will proceed the phase-II study. Clinical trial information: UMIN000020475.

数々の抗腫瘍薬が開発され外科的な切除術が進歩を遂げている中で未だ膵癌のコントロールは不良である．特に固形癌に有効な副作用の少ない抗腫瘍薬は殆ど存在しない．こうした状況の中で難治膵癌に対する副作用の少ない新規の抗腫瘍薬の開発が切望されている．腫瘍溶解性ウイルスを用いる癌治療は，ウイルスが癌細胞に感染し増殖して内部から癌細胞を破壊するため，従来の遺伝子治療よりも強力な治療効果が期待される．また，最近では腫瘍特異的リンパ球など，癌ワクチンすなわち全身療法としての効果も明らかにされつつある．文献上の検索では，新薬として認可された物やPhase III臨床試験として，全世界で癌患者に対し腫瘍溶解性ウイルスによる癌治療が行われている現状がある．腫瘍溶解性ウイルスの中でも特に当科で行われた膵癌に対する基礎研究と臨床研究に焦点を当てて解説する．

Background Pancreaticoduodenectomy and distal pancreatectomy for lesions of the neck or body of the pancreas sacrifice a large amount of normal pancreatic tissue. Middle pancreatectomy (MP) is a parenchyma sparing technique that reduces the risk of postoperative endocrine and exocrine insufficiency. This study aims to evaluate the perioperative and long-term results of MP and to clarify whether MP can be performed with outcomes comparable with traditional pancreatectomies. Method Twenty-six patients who underwent MP for benign or low-grade malignant tumor of the pancreas between 1991 and 2006 at the Department of Surgery II, Nagoya University Graduate School of Medicine, were identified. Their outcomes were compared with 2 separate control groups, 35 left-side pancreatectomies (LSP) and 60 right-side pancreatectomies (RSP). Results The mean operating time of the MP group was 295 minutes, which was significantly shorter than that for RSP (P = .0001). The rate of pancreatic fistula formation was higher in the MP group than in the 2 control groups, although the differences did not reach statistical significance. After a mean follow-up of 71 months, postoperative endocrine function was equivalent to the pre-operative values in the MP group, and none of the patients developed diabetes mellitus postoperatively. Only 1 patient in the MP group required enzyme substitution postoperatively for exocrine insufficiency. The MP group was inclined to be superior to the other 2 control groups in terms of postoperative nutritional status. Conclusion Middle pancreatectomy is a reasonable technique that is indicated for selected patients with benign or low malignant tumors in the neck and body of the pancreas. Middle pancreatectomy seems to result in better preservation of exocrine and endocrine functions as well as in better nutritional status postoperatively.

We have experienced 67 cases of pancreatic head resection with segmental duodenectomy (PHRSD) for benign or low-grade malignant tumor of the pancreatic head region. Here we introduce our operative technique for these 67 cases. Pancreatic head resection is performed with segmental duodenectomy including minor and major papilla. By conserving the right gastric artery and the gastroduodenal artery, 5–7 cm of the first portion of the duodenum is preserved with good arterial circulation. In addition, by conserving the anterior inferior pancreatoduodenal artery, the third portion and anal side or the second portion of the duodenum are preserved with good arterial circulation. Cholecystectomy is performed. The procedure is completed by resection of the pancreatic head with 3–4 cm of segmental duodenectomy including minor and major papilla. Reconstruction of the alimentary tract is performed with pancreatogastrostomy, end-to-end duodenoduodenostomy and end-to-side choledochoduodenostomy. In 67 cases with diseases of the pancreatic head region, chiefly intraductal papillary mucinous neoplasms, this procedure was successfully performed without operative or hospital death. Postoperative quality of life was quite satisfactory. Total resection of the pancreatic head can be performed safely and effectively by this procedure.

Background/Aims Hepatocarcinogenesis is a multifactorial, multistep process that involves the activation of oncogenes or the inactivation of tumor suppressor genes throughout the different stages of hepatocellular carcinoma (HCC) progression. NPRL2 is one of the candidate tumor suppressor genes identified on chromosome 3p21.3, a region which frequently contains genetic abnormalities found in the early stages of the development of various human cancers. In the current study, we aimed to evaluate NPRL2 expression in HCC and to explore the prognostic significance of NPRL2. Method We investigated NPRL2 mRNA expression in 70 HCC specimens, using quantitative real-time reverse transcription polymerase chain reaction analysis, and the correlation between NPRL2 expression and clinicopathologic parameters. Results NPRL2 mRNA was found to be expressed equally in both HCC tissues and corresponding non-cancerous liver tissues. However, higher NPRL2 expression correlated significantly with tumor size (P = 0.0062) and serum PIVKA-II levels (P = 0.0002). Univariate and multivariate analyses revealed that higher NPRL2 mRNA expression was an independent prognostic factor for overall survival (risk ratio 0.39; P

We present our experience in the treatment of nonfunctioning neuroendocrine pancreatic tumors (NFNPTs) to define the clinical and pathological characteristics and to suggest proper management.The records of 17 patients with NFNPTs operated on between 1998 and 2008 were retrospectively reviewed, and all tumors were classified clinicopathologically as benign, uncertain, and malignant, based on the World Health Organization (WHO) classification of neuroendocrine tumors.There were four benign, six uncertain, and seven malignant NFNPTs. The most frequent symptoms were abdominal pain (five patients) and obstructive jaundice (one patient). Most of these symptomatic patients had malignant tumors. Mean tumor size of benign, uncertain, and malignant tumors were 1.0 +/- 0.3, 3.2 +/- 1.6, and 5.3 +/- 2.4 cm, respectively. Metastatic lesions of malignant tumors were lymph node (six patients), liver (four patients), and adrenal gland (one patient). Six of seven patients with malignant tumors underwent curative rejection. There were recurrences in four of six patients with curatively rejected malignant tumors. Two patients underwent more rejection, three patients received systemic chemotherapy, and two patients underwent radiofrequency ablation and transcatheter arterial chemoembolization for liver metastases. Survival of patients with malignant tumors was significantly shorter than that of patients with benign and uncertain tumors. However, three patients with malignant tumors had long survival of more than 3 years, even with metastases or recurrences.Aggressive surgical resection should be performed in patients with resectable NFNPTs, even with metastases. Even when a tumor was unresectable or there were recurrences, long-time palliation could be achieved by a multidisciplinary approach.

症例は65歳の男性で，糖尿病にて通院中，血液検査異常あり，CTを施行し肝内胆管拡張および肝腫瘍を指摘された．結腸癌の既往があり，転移性肝癌も疑われ内視鏡検査が施行され胃癌を指摘された．胃癌合併の肝内胆管癌を疑い幽門側胃切除，肝右葉切除を施行した．切除標本では大腸癌の肝転移の所見であった．本症例は胆管内腫瘍栓を伴う大腸癌肝転移の特徴を有した貴重な症例であり，原発巣切除から肝再発の診断まで最長期間例であった．

This paper presents the dynamic properties of undisturbed and remolded clays and sand-clay mixtures based on the results of undrained hollow cylindrical torsional cyclic simple shear tests. The clays were obtained from different sites having a wide range of plasticity, covering fluvial and marine sediments. The main focus of this investigation is the dynamic properties of sand-clay mixtures whose properties are intermediate between those of clays and sands. The initial shear moduli are examined in terms of fines content, and conventional plasticity index. An equivalent plasticity index has been defined in the present investigation and a better correlation is obtained between the initial shear modulus of sand-clay mixtures and this parameter than with the conventional plasticity index. Further, a simple method has been suggested to determine the equivalent plasticity index based on the conventional consistency limit tests and grain size analysis. An empirical correlation for predicting the initial shear modulus is also proposed.

A series of undrained cyclic torsional simple shear tests using hollow cylindrical torsional shear apparatus was carried out to investigate the dynamic shear moduli and damping properties of clayey specimens with various sand contents and plasticity indices. The clayey soils used were collected from various sites along the coast of west Japan. Among these clayey soils, a clay sample with intermediate plasticity and another with high plasticity were mixed with silica sand at different proportions in order to examine the dynamic properties of sand-clay mixtures. In addition, experiments were carried out on undisturbed and remolded natural clay specimens with various plasticities. The effects of plasticity, loading frequency and confining pressure on the strain dependent normalized shear modulus and damping ratio were examined. Based on the results, empirical correlations for predicting the normalized shear modulus and damping ratio of remolded sand-clay mixtures at various shear strain levels were proposed.

症例は60歳の男性で, 悪心, 心窩部痛を主訴に近医受診し, 血液検査にて閉塞性黄疸を指摘され入院となった. 腹部CTでは膵頭部・尾部の2か所に造影効果の乏しい腫瘤を認め, 腹部血管造影検査では腫瘤による脾動静脈浸潤が疑われた. 膵臓の多重癌との術前診断により手術を施行した. 小腸間膜には数個の結節を認めたが肉芽腫によるものであり腹膜播種とは診断されず, また膵全体は腫瘤により硬化し上腸間膜静脈浸潤も認められたため, 上腸間膜静脈合併膵全摘術を施行した. 術後病理組織学的検査では多核巨細胞を混じた類上皮細胞による肉芽腫形成が著しく, 肉芽腫性膵炎と診断された. 膵臓に肉芽腫を形成する疾患の鑑別診断として各種検査を施行したが, 著明な肉芽腫形成を伴った腫瘤形成性膵炎と最終診断した. 我々が検索するかぎり本邦において類似症例の報告は認めない.

The usefulness of enteral nutrition via a nasointestinal tube for patients who develop postoperative pancreatic fistula (POPF) after miscellaneous pancreatectomy procedures has been reported. However, no clear evidence regarding whether oral intake is beneficial or harmful during management of POPF after distal pancreatectomy (DP) is currently available. To investigate the effects of oral food intake on the healing process of POPF after DP. Multi-institutional randomized controlled trial in Nagoya University Hospital and 4 affiliated hospitals. Patients who developed POPF were randomly assigned to the dietary intake (DI) group (n=15) or the fasted group (no dietary intake [NDI] group) (n=15). The primary endpoint was the length of drain placement. No significant differences were found in the length of drain placement between the DI and NDI groups (12 [6-58] and 12 [7-112] days, respectively; P=0.786). POPF progressed to a clinically relevant status (grade B/C) in 5 patients in the DI group and 4 patients in the NDI group (P=0.690). POPF-related intra-abdominal hemorrhage was found in 1 patient in the NDI group but in no patients in the DI group (P=0.309). There were no significant differences in POPF-related intra-abdominal hemorrhage, the incidence of other complications, or the length of the postoperative hospital stay between the 2 groups. Food intake did not aggravate POPF and did not prolong drain placement or hospital stay after DP. There may be no need to avoid oral DI in patients with POPF.

To determine which indicators, anatomical nodal metastasis (Japan Pancreas Society, JPS), number of positive lymph nodes (PLN), or lymph node ratio (LNR), is the best means of assessing lymph node involvement in pancreatic cancer.This retrospective study analyzed 275 patients with pancreatic cancer treated at a single institution. Survival curves according to the JPS, PLN, or LNR were assessed by the Kaplan-Meier method. Prognostic value of each classification was explored by Cox regression analysis after adjustments for clinical factors.Multivariate analysis showed that, relative to n0 in the JPS, hazard ratios (HR) in n1, n2, and n3 were 1.72, 1.73, and 2.75, respectively, with no difference in survival between n1 and n2. Relative to PLN of 0, the HR in the PLN categories of 1∼2, 3, and3 were 1.39, 1.65, and 3.03, respectively. Relative to LNR of 0, the HR in the categories of 0 LNR ≤ 0.1, 0.1 LNR ≤ 0.2, and LNR 0.2 were 1.27, 2.00, and 5.58, respectively. An incremental increase in the HR was observed as the LNR category progressed, and differences between the survivals were distinct when stratified by the LNR.The LNR was an accurate predictor of survival among three assessment strategies and could be proposed as a candidate for use as N categories, pending validation studies.

To find predictive factors among computed tomography (CT) findings to identify pancreatic neuroendocrine tumors G2 of World Health Organization classification.Thirty-seven patients with pancreatic neuroendocrine tumors underwent multiphase contrast enhanced CT (unenhanced, arterial, pancreatic, portal and equilibrium phase), and attenuation values and imaging findings were examined. A receiver operating characteristic curve analysis was performed, and association between imaging findings and World Health Organization classification was evaluated.Mean CT attenuation value of NET G1 was significantly higher than that of NET G2 throughout the arterial, pancreatic, and portal phases. Receiver operating characteristic analysis according to tumor size revealed sensitivity: 83.3%, specificity: 92.0% and area under the curve (AUC): 0.853, whereas that of corrected true enhancement values in the pancreatic phase revealed sensitivity: 91.7%, specificity: 84.0% and AUC: 0.897, which showed the highest AUC. Specific CT findings, such as irregular tumor contour, vessel involvement, and cystic degeneration/necrosis, were significantly associated with NET G2, but not to the extent of CT attenuation value and tumor size.The CT enhancement in the pancreatic phase, and irregularity, vessel involvement, and cystic degeneration/necrosis were significant predictors of NET G2. These parameters might help in differentiating between NET G1 and G2, providing a basis for appropriate treatment.

Laparoscopic (assisted) distal gastrectomy (LDG) with radical lymphadenectomy for gastric cancer has been widely conducted, particularly in the Far East. Peripancreatic inflammatory fluid collection (PIFC) is a serious and frequent postoperative complication after LDG for gastric cancer. The aim of this study was to evaluate the diagnostic performance of drain amylase content (D-AMY) for clinically relevant PIFC after LDG. Two hundred and sixty-four patients who underwent LDG with prophylactic drains were enrolled. The predictive value of D-AMY on postoperative day (POD) 1 and POD 3 in the diagnosis of PIFC was evaluated. Twenty (7.6 %) patients experienced postoperative PIFC. Area under the curve in terms of receiver operating characteristics curve analysis of D-AMY on POD 1 was 0.801, and the optimal cutoff value for prediction of PIFC was 904 IU/l, with 98.2 % negative predictive value. Another cutoff was proposed as 4078 IU/l, with 92.2 % specificity. Multivariable analyses identified D-AMY on POD 1 ≥900 and ≥4000 IU/l as independent diagnostic factors for PIFC. Among patients at high risk of PIFC (D-AMY on POD 1 ≥900 IU/l), those who on POD 3 retained D-AMY value in excess of 31.2 % of the D-AMY value on POD 1 were more likely to experience PIFC compared with those with a pronounced decrease in D-AMY. D-AMY on POD 1 serves as a predictive factor for clinically relevant PIFC after LDG. Time-dependent changes in D-AMY can also be used for determining management of drains in patients at high risk of PIFC.

The aim of this study was to investigate the efficacy and mechanism of action of combined S-1 and nab-paclitaxel in pancreatic cancer.Three human pancreatic cancer cell lines were treated with S-1, nab-paclitaxel, alone or in combination. Mice bearing subcutaneous xenograft of the cell line, PANC-1, were treated with the same drugs.The growth-inhibitory effect of combined S-1 and nab-paclitaxel was greater than that of the individual drugs, and the combination index value indicated that S-1 and nab-paclitaxel had a synergistic effect in vitro. The combination of S-1 and nab-paclitaxel showed greater efficacy in vivo than monotherapy, and the growth-inhibitory effect was significantly greater when compared with the controls (P = 0.009), although no significant reduction in body weight was observed. Fractional tumor volume analysis indicated that the combination had a synergistic effect. Tumor stroma staining with α-smooth muscle actin was significantly decreased by nab-paclitaxel (P 0.001) while the number of CD31-stained microvessel lumina was significantly increased by the combination therapy when compared with the control (P = 0.046).S-1 and nab-paclitaxel had a synergetic effect in preclinical studies with good tolerability, and may play a role in stromal depletion and tumor angiogenesis. J. Surg. Oncol. 2016;113:413-419. © 2016 Wiley Periodicals, Inc.

The clinical implications of single nucleotide polymorphisms (SNPs) in CD44 remain unclear. This study examined the relationships of CD44 SNPs with clinicopathological parameters and prognosis in Japanese gastric cancer patients.The CD44 SNPs were analyzed in 11 gastric cancer cell lines and 517 clinical specimens. The expression of CD44 standard (CD44s) and CD44 variant 9 isoform (CD44v9) transcripts were measured by quantitative real-time polymerase chain reaction.The CD44 rs187116 A/A, A/G, and G/G genotypes were present in 10.3%, 45.1%, and 44.7% of patients, respectively. The presence of CD44 rs187116 A/G or G/G genotypes was significantly associated with positive peritoneal washing cytology (P = 0.012). Disease-free survival of patients with these genotypes was significantly worse than in those with the A/A genotype (P = 0.039). Multivariate analysis showed that the CD44 rs187116 was independently prognostic of disease-free survival (P = 0.047). The CD44s/CD44v9 ratio was significantly lower in patients with the CD44 rs187116 A/A genotype than in those with the A/G (P = 0.046) and G/G (P = 0.047) genotypes.The CD44 rs187116 genotype could predict disease recurrence in Japanese gastric cancer patients, and the SNP was associated with CD44 isoform switching.

Gastric cancer (GC) is a major global health problem that urgently requires novel molecular biomarkers for patient stratification as well as therapeutic targets. Anosmin-1 (ANOS1) gene encodes a cell adhesion molecule that plays diverse roles in multiple malignancies. We performed global expression profiling of GC cell lines and small interfering RNA (siRNA) experiments to determine the effect of ANOS1 expression on phenotype. We evaluated the association of ANOS1 mRNA and protein levels in patients' tissue and sera with clinicopathological factors of GC subtypes. Differential expression of ANOS1 mRNA by GC cell lines correlated positively to levels of ITGAV, FOXC2 and NODAL mRNAs and inversely with those of TFPI2. Inhibiting ANOS1 expression decreased the proliferation, invasion and migration of GC cells. The mean level of ANOS1 mRNA was significantly higher in 237 GC tissues compared with the corresponding noncancerous adjacent tissues. Elevated ANOS1 levels associated significantly with the phenotypes of GC, shorter disease-free and overall survival. ANOS1 expression was a more significant prognostic marker for diffuse and distal nondiffuse GC. ANOS1 concentrations in sera increased sequentially in sera of healthy subjects, localized GC and disseminated GCs. Prognosis was worse for patients with preoperative serum ANOS1 ≥ 600 pg/ml compared with those with600 pg/ml. ANOS1 may represent a biomarker for GC phenotypes and as a target for therapy.