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OBJECTIVES This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC). METHODS Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study. RESULTS Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, β, and γ. CONCLUSIONS Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.

Objectives The aim of this dual‐center randomized controlled trial was to determine the optimal duration of antimicrobial prophylaxis in patients treated with pancreaticoduodenectomy (PD) who underwent preoperative biliary drainage (PBD) but were without cholangitis. Background Some reports showed that PBD in patients undergoing pancreatectomy increased the rate of perioperative complications. However, no clinical trial has evaluated the optimal duration of antimicrobial prophylaxis with a focus on patients who underwent PD following PBD. Methods A total of 82 patients who underwent PD between March 2012 and December 2016 were randomly assigned to either a 1‐day group (n = 40), in which cefozopran (CZOP) as antimicrobial prophylaxis was given only on the day of surgery, or a 5‐day group (n = 42), in which CZOP was given for 5 consecutive days beginning on the day of surgery. We evaluated the incidence of infectious and other complications after PD. Results Outcomes were significantly better in the 1‐day group compared with the 5‐day group (P

Hematogenous recurrence is a challenging clinical finding that often leads to fatalities of patients with gastric cancer. Therefore, the identification of specific biomarkers and potential therapeutic target molecules for hematogenous recurrence is required to improve the outcomes of these patients. Here, transcriptome and bioinformatics analyses were conducted to uncover candidate molecules differentially expressed in patients with hematogenous recurrence of gastric cancer. One potential candidate identified was asialoglycoprotein receptor 2 (ASGR2), and siRNA experiments were conducted to determine the effect of manipulating ASGR2 expression has on cell phenotypes. ASGR2 mRNA expression analysis using quantitative real-time reverse-transcription PCR was conducted with stage II/III gastric cancer clinical specimens (n = 95). Transcript levels were increased in gastric cancer cells as compared with a control nontumorigenic epithelial cell line. Knockdown of ASGR2 decreased the adhesion and migration potential. Thus, although gastric cancer cell–invasive activity was significantly decreased by knockdown, forced expression of ASGR2 promoted invasive activity. Using a mouse hepatic metastasis model, knockdown of ASGR2 resulted in the absence of hepatic metastasis formation. High ASGR2 expression in primary gastric cancer tissues was an independent predictor of shorter disease-free and overall survival. Finally, patients with high ASGR2 expression were more likely to have a high cumulative rate of hematogenous recurrence but not peritoneal or nodal recurrence. Implications: ASGR2 expression is associated with the malignant phenotypes in gastric cancer and represents a specific biomarker of hematogenous recurrences after curative resection for gastric cancer. Mol Cancer Res; 16(9); 1420–9. ©2018 AACR.

The association between neoadjuvant therapy (NAT) and nutritional status in pancreatic cancer (PC) is unknown. The aim of this study was to assess the impact of NAT on nutritional status. Overall, 161 patients who underwent pancreatoduodenectomy for PC between August 2010 and March 2017 were enrolled and were divided into two groups: the neoadjuvant group (NAG; n = 67) and the control group (CG; n = 94). Based on relative dose intensity (RDI), patients in the NAG group were further divided into RDI ≥ 80% (n = 39) and RDI

Purpose The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC). Patients and Methods Patients with untreated mCRC were randomly assigned to receive either CapOX plus bevacizumab (CapOX/BEV arm: bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 2,000 mg/m2 on days 1–14, every 3 weeks) or CapIRI plus bevacizumab (CapIRI/BEV arm: bevacizumab 7.5 mg/kg and irinotecan 200 mg/m2 on day 1 and capecitabine 1,600 mg/m2 on days 1–14, every 3 weeks). The primary endpoint was overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results A total of 107 patients were enrolled. The intent-to-treat population comprised 54 patients in the CapOX/BEV arm and 53 patients in the CapIRI/BEV arm. The median follow-up period was 35.5 months. ORR was 56% in the CapOX/BEV arm and 55% in the CapIRI/BEV arm. Median PFS and OS were 12.4 and 26.7 months in the CapOX/BEV arm and 11.5 and 28.7 months in the CapIRI/BEV arm, respectively. The frequencies of hematological and nonhematological adverse events above grade 3 were 13% and 30% in the CapOX/BEV arm and 25% and 23% in the CapIRI/BEV arm, respectively. Conclusion CapOX plus bevacizumab and CapIRI plus bevacizumab are equally effective and feasible as the first-line treatments in Japanese patients with mCRC. Implications for Practice The CCOG-1201 study was designed to evaluate the efficacy and safety of capecitabine and oxaliplatin plus bevacizumab and capecitabine and irinotecan plus bevacizumab as a first-line treatment in Japanese patients with metastatic colorectal cancer. This article reports on the trial and efforts to define the role of these regimens, including the effect of KRAS status and UGT1A1 polymorphisms in metastatic colorectal cancer.

Background In distal pancreatectomy (DP), it is customary to ligate and divide the splenic vein after isolating it from the pancreatic parenchyma. This is considered essential to prevent disruption of the stump of the splenic vein and consequent intra-abdominal haemorrhage in the event of pancreatic fistula (PF). However, this procedure can be technically demanding, especially when the vein is firmly embedded in the pancreatic parenchyma. The objective of the COSMOS-DP trial is to confirm the non-inferiority of resection of the splenic vein embedded in the pancreatic parenchyma compared with the conventional technique of isolating the splenic vein before resection during DP using a mechanical stapler. Methods Patients with diseases of the pancreatic body and tail whose pancreatic parenchyma and splenic vein can be divided concurrently during open or laparoscopic DP are considered eligible for inclusion. This study is designed as a multicentre prospective randomised phase III trial. Eligible patients will be centrally randomised to either Arm A (resection of the splenic vein after isolation from the pancreatic parenchyma) or Arm B (co-resection of the vein together with the pancreas). This study aims to establish the non-inferiority of the safety of Arm B compared with that of Arm A; the primary endpoint is the incidence of PF (ISGPF grade B/C). Discussion The COSMOS-DP trial will establish the safety of this procedure, such that it can be recommended with more confidence. The use of this procedure will likely result in significant reductions in operative time and blood loss during DP. Trial registration ClinicalTrials.gov, NCT02871804. Registered on 27 July 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2756-7) contains supplementary material, which is available to authorized users.

Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P P P = 0.03) was a significant independent prognostic factor for patients with PC. Additionally, LOX inhibition significantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.

Liver metastasis remains a serious problem in the management of gastric cancer (GC). Our aims were to identify through transcriptome analysis a molecule that mediates hepatic metastasis in GC, and to evaluate its potential as a diagnostic marker and a therapeutic target. The effects of knocking out a relevant molecule using genome editing were evaluated in vitro experiments and in mouse xenograft models. Expression levels of candidate molecule in 300 pairs of gastric tissues were determined to assess whether differentially expressed genes predicted hepatic recurrence, metastasis, or both. Transcriptome data identified the overexpression of synaptotagmin VII (SYT7) in GC tissues with hepatic metastasis. Its expression in the GC cell lines was high, particularly in those that exhibited a differentiated phenotype, and positively correlated with the expression of SNAI1 and TGFB3, and inversely with RGS2. SYT7 knockout inhibited the proliferation of GC cells, indicated by increased apoptosis with activated caspase and loss of mitochondria membrane potential, G2/M cell-cycle arrest and attenuated cell migration, invasion, and adhesion. The tumorigenicity of SYT7-knockout cells was moderately reduced in a mouse model of subcutaneous metastasis in which the levels of BCL2 and HIF1A were decreased and was more strikingly attenuated in a model of hepatic metastasis. The SYT7 levels in the primary GC tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. SYT7 represents a tool for prediction and monitoring of hepatic metastasis from GC as well as being a promising therapeutic target.

Background Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. Methods Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer. Results Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence. Conclusion SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.

INTRODUCTION Optical trocar access is a technique to place the initial trocar in laparoscopic surgery. With optical trocar access, each tissue layer can be visualized before insertion, which can help prevent organ injury, and air leaks at the trocar site can be minimized even in obese patients. The aim of this study was to compare the time needed for trocar insertion using optical trocar access and an open method in patients who underwent laparoscopic gastrointestinal surgery. METHODS We reviewed our prospectively collected database and identified 384 patients who underwent laparoscopic gastrointestinal surgery involving initial trocar insertion near the umbilicus by either the optical trocar access or the open method. Before the two methods were compared, propensity score matching was used to adjust for essential variables between the optical trocar access and open groups. RESULTS Patients categorized in the optical trocar access and open groups were matched one-to-one by propensity score matching, and 137 pairs of patients were generated. The time needed for trocar insertion was significantly shorter in the optical trocar access group than in the open group (36.6 vs 209.8 s, P

Although peritoneal metastasis is a serious concern in patients with gastric cancer, no acceptable and specific biomarker is available. We aimed to identify a candidate biomarker to predict peritoneal metastasis of gastric cancer. Metastatic pathway-specific transcriptome analysis was conducted by comparison of patient groups with no recurrence and with peritoneal, hepatic, and nodal recurrence. Fifteen cell lines and 262 pairs of surgically resected gastric tissues were subjected to messenger RNA (mRNA) expression analysis. Polymerase chain reaction array analysis was performed to explore coordinately expressed cancer-related genes. To evaluate the in situ protein localization and expression patterns, immunohistochemical staining was performed. From transcriptome data, troponin I2 (TNNI2) was identified as a candidate molecule specifically overexpressed in gastric cancer prone to peritoneal metastasis. TNNI2 mRNA was expressed at differential levels, independent of differentiated phenotype of cell lines. Epithelial to mesenchymal transition-related genes, tumor inhibitor of metalloproteinase 1 (TIMP1), and vacuolar protein sorting 13 homolog A (VPS13A) were expressed with TNNI2 at correlation coefficient > 0.7. The optimal cutoff of TNNI2 expression was determined as 0.00017. High TNNI2 expression was significantly and specifically associated with peritoneal metastasis and served as an independent risk marker for peritoneal recurrence after curative gastrectomy. Prevalence of peritoneal recurrence increased in parallel with staining intensity of TNNI2. TNNI2 expression in gastric tissues may serve as a specific biomarker for prediction of peritoneal metastasis of gastric cancer and contribute to improvement of patient management.

// Mitsuro Kanda 1 , Kenta Murotani 2 , Haruyoshi Tanaka 1 , Takashi Miwa 1 , Shinichi Umeda 1 , Chie Tanaka 1 , Daisuke Kobayashi 1 , Masamichi Hayashi 1 , Norifumi Hattori 1 , Masaya Suenaga 1 , Suguru Yamada 1 , Goro Nakayama 1 , Michitaka Fujiwara 1 and Yasuhiro Kodera 1 1 Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan Correspondence to: Mitsuro Kanda, email: m-kanda@med.nagoya-u.ac.jp Keywords: gastric cancer; expression panel; prognosis; biomarker Received: January 05, 2018 Accepted: February 27, 2018 Published: April 10, 2018 ABSTRACT Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506–0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents ( MAGED2, SYT8, BTG1 , and FAM46 ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1–3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.

Objective: To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). Background: Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. Methods: We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. Results: Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. Conclusions: SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC., ファイル公開：2019-03-01

To investigate the efficacy and safety of planned postoperative adalimumab (ADA) therapy for Japanese patients with Crohn’s disease (CD). The subjects of this study were 26 patients who underwent bowel resection for CD. All patients received subcutaneous injections of ADA 160/80 mg at the time of surgery and 2 weeks later, followed by 40 mg every 2 weeks thereafter. The primary endpoint of this study was the incidence of endoscopic recurrence, defined by Rutgeerts endoscopic recurrence scale ≥ i2, 1 year after surgery. After the median follow-up period of 41.3 months, the median number of treatments with ADA was 56 and the median time-to-treatment failure was 25.6 months. Endoscopic recurrence was observed in 34.6% of the patients 1 year after surgery. Univariate analyses showed that preoperative ADA therapy was significantly associated with endoscopic recurrence. Clinical recurrence developed in 16.7% of the patients within 1 year after surgery. Secondary surgery for recurrence was not required. Although adverse events (≥ grade 3) were experienced by 15.4% of patients, none was withdrawn from this study. Planned postoperative ADA therapy reduced the incidence of endoscopic and clinical recurrence after bowel resection in Japanese patients with CD. This trial is registered with the University Hospital Medical Information Network (UMIN000007514).

Background/Aims: Do serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels serve as prognostic indicators in patients with gastric cancer (GC)? This is a question that has long been disputed. The aim of this study was to evaluate the significance of perioperative serum levels of CEA and CA19-9 for predicting the recurrence and long-term survival after patients with pT2-4 GC undergo curative gastrectomy. Methods: This study included 251 patients with radically resected pT2-4 GC without preoperative treatment. Associations between the preoperative and postoperative serum levels of CEA or CA19-9 and postoperative long-term outcomes and recurrence patterns were evaluated. Results: Preoperative CEA >5.0 ng/mL was an independent prognostic factor of overall survival. Elevation of both preoperative CEA and CA19-9 levels showed no synergistic adverse effects on prognosis. Preoperative levels of these markers achieved superior predictive performance compared with the postoperative values. Adverse prognosis is significantly associated with persistent elevation of CEA levels before and after gastrectomy. Elevation of CEA levels, particularly at postoperative measurement, was significantly associated with hematogenous recurrence. Conclusion: Determination of perioperative CEA levels facilitated predictions of recurrence patterns and prognosis among patients with pT2-4 GC who underwent curative gastrectomy., ファイル公開日: 2018/12/01

The medical applications of nonequilibrium atmospheric pressure plasma in cancer therapy have attracted attention. We previously reported on the antitumor effect of plasma-activated medium. However, this approach requires plasma-activated liquids that are administrable to the human body. In this study, we produced plasma-activated lactated Ringer’s solution (PAL) and evaluated its antitumor effect and mechanism. Furthermore, we evaluated the effect of the intraperitoneal administration of PAL using a peritoneal dissemination mouse tumor model. The antitumor effect of PAL on pancreatic cancer cell lines was evaluated using proliferation and apoptosis assays. In addition, cellular reactive oxygen species (ROS) generation was examined. The role of ROS was assessed using a proliferation assay with N-acetyl cysteine (NAC). An adhesion assay was performed to evaluate the effect of PAL on cell adhesion. Finally, pancreatic cancer cells stably expressing luciferase (AsPC-1/CMV-Luc) were injected intraperitoneally into mice, followed by intraperitoneal injection of PAL. Peritoneal dissemination was monitored using in vivo bioluminescent imaging. The antitumor effect of PAL was shown in all cell lines in vitro. The TUNEL assay showed that PAL induced apoptosis. ROS uptake was observed in PAL-treated cells, and the antitumor effect was inhibited by NAC. Cell adhesion also was suppressed by PAL. The intraperitoneal administration of PAL suppressed the formation of peritoneal nodules in vivo. Our study demonstrated the antitumor effects of PAL in vitro and in vivo. Intraperitoneal administration of PAL may be a novel therapeutic option for peritoneal metastases.

Background: Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy. Methods: A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome. Results: Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence. Conclusions: Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.

On 16 April 2016, a moment magnitude (Mw) 7.0 earthquake struck the Island of Kyushu, Japan. Two major foreshocks (Mw 6.2 and Mw 6.0) contributed to devastation in Kumamoto City, Mashiki Town and in the mountainous areas of the Mount Aso volcanic caldera. This report summarises geotechnical and geological aspects of the earthquakes that were observed during a field investigation conducted by the NZSEE Team in collaboration with Japanese engineers and researchers. Many houses and other buildings, roads, riverbanks, and an earth dam, either on or adjacent to the surface fault rupture or projected fault trace, were severely damaged as a result of both the strong ground shaking and permanent ground displacement. In the Mount Aso volcanic caldera, traces of medium to large scale landslides and rock falls were frequently observed. A number of landslides impacted homes and infrastructure, and were reported to have killed at least 10 people out of the 69 confirmed deaths associated with the earthquake. In a few suburbs of Kumamoto City and in Mashiki Town, localised liquefaction took place, causing lateral spreading, differential settlements of the ground and riverbanks, sinking and tilting of buildings, foundation failures, cracks on roads, and disruption of water and sewage pipe networks. The overall effects from liquefaction related hazards appeared relatively minor compared to the damage caused by shaking, landslides and surface fault rupture. Based on the field survey, key findings are highlighted and recommendations to NZ engineering practice are made in the report.

The albumin–bilirubin (ALBI) score was initially developed for assessing liver dysfunction severity and was suggested to have prognostic value in patients with hepatocellular carcinoma. We aimed to evaluate the prognostic impact of ALBI grade in patients with advanced gastric cancer (GC) after radical gastrectomy. This study included 283 patients who underwent radical gastrectomy for pT2-4 GC without preoperative treatment. ALBI was calculated as follows: (log10 bilirubin (μmol/L) × 0.66) + (albumin (g/L) × −0.0852) and categorized into grades 1 (≤−2.60), 2 (−2.60

Background Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker. Methods We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection. Results GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences. Conclusions Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection. Electronic supplementary material The online version of this article (10.1186/s12885-017-3629-2) contains supplementary material, which is available to authorized users.

// Mitsuro Kanda 1 , Kenta Murotani 2 , Hiroyuki Sugimoto 1 , Takashi Miwa 1 , Shinichi Umeda 1 , Masaya Suenaga 1 , Masamichi Hayashi 1 , Norifumi Hattori 1 , Chie Tanaka 1 , Daisuke Kobayashi 1 , Suguru Yamada 1 , Michitaka Fujiwara 1 and Yasuhiro Kodera 1 1 Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan Correspondence to: Mitsuro Kanda, email: m-kanda@med.nagoya-u.ac.jp Keywords: hepatocellular carcinoma, biomarker, prognosis, expression panel Received: June 22, 2017 Accepted: July 25, 2017 Published: August 19, 2017 ABSTRACT Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1:2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate molecular markers were determined using quantitative reverse-transcriptase PCR. In the discovery set, an expression panel was developed according to the concordance index (C-index) values for overall survival from all 4095 combinations of the 12 candidate molecular markers. Expression scores was determined with weighting according to the coefficient in a Cox regression, and patients were classified into grade 1, 2 and 3. Reproducibility was then tested in the validation set. A panel consisting of four markers, PRMT5 , MAGED4 , DPYSL3 and AJAP1 was selected as the optimal and most well-balanced set with a C-index value of 0.707. Patient prognosis was clearly stratified by the expression grade using this panel. In the validation set, both overall and disease-free survival rates decreased incrementally with as the grade increased. Higher grades were significantly associated with tumor multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was increased in grade 3 patients. The integrated multigene expression panel clearly stratified HCC patients into low, intermediate and high risk.

The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC‑associated molecular events to improve the diagnosis, and treatment of this disease. Non‑specific cytotoxic cell receptor protein 1 (NCCRP1) was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of NCCRP1 in ESCC remains unclear. To elucidate the oncological roles of NCCRP1 in ESCC, NCCRP1 expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different NCCRP1 mRNA expression levels and all exhibited hypermethylation of the NCCRP1 promoter, but no copy number loss. Additionally, NCCRP1 expression was determined in 213 surgically resected esophageal tissue samples. NCCRP1 mRNA expression levels were reduced in ESCC tissues compared with corresponding non‑cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low NCCRP1 expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high NCCRP1 expression group. Additionally, multivariate analysis revealed that low NCCRP1 expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08‑2.87; P=0.022). The findings of the current study indicate that NCCRP1 acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.

AIM To identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors. METHODS Three-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy (distal gastrectomy or total gastrectomy) were included in the analysis. Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications (grade II or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage. RESULTS Sixty-six patients (21.1%) experienced grade II or higher postoperative complications. The platelet-lymphocyte ratio (PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value (0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71 (sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94 (95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications (OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications. CONCLUSION The preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer.

The epithelial-to-mesenchymal transition (EMT) is an initial, critical step in hepatocellular carcinoma (HCC) tumor invasion and metastasis. Frizzled 2 (Fzd2) expression might drive EMT through the non-canonical Wnt pathway, one of the various EMT signaling pathways. The expression of epithelial (E-cadherin) and mesenchymal (vimentin) markers, as well as that of Wnt5b, Stat3, IL-6, Jak2 and Fzd2, were measured in 15 HCC cell lines. The EMT status (vimentin to E-cadherin mRNA expression ratio), Fzd2 mRNA expression, and pSTAT3 protein expression were assessed by immunostaining in 100 HCC patients, and correlations of their expression with clinicopathological factors and prognosis were analyzed. Cell proliferation, migration, and invasiveness were assessed after Fzd2 knockdown. Fzd2 expression was significantly correlated with a mesenchymal phenotype in the HCC cell lines. Treatment of the cell lines with Fzd2 siRNA resulted in significantly reduced migration and invasiveness but did not affect proliferation. A significant correlation was detected between the EMT status and Fzd2 expression in the HCC patients. Multivariate analysis revealed that Fzd2 expression was an independent predictor of recurrence (P=0.034). Patients with high Fzd2 expression had significantly poorer recurrence‑free survival than those with low expression (P=0.03). Finally, pSTAT3 expression was significantly correlated with the EMT and Fzd2 status (P=0.0028, and P=0.0066, respectively). Fzd2 expression induced EMT and enhanced cell migration and invasiveness, and it might be a novel predictor of HCC recurrence. Furthermore, Stat3 might be controlled by both the Wnt5/Fzd2 and IL-6/Jak2 signaling pathways and play an important role in EMT.

The Charlson age comorbidity index (CACI) is a useful measure of comorbidity to standardize the evaluation of surgical patients and has been reported to predict postoperative mortality in various cancers.A total of 379 patients who underwent R0/R1 resection for pancreatic cancer between 2003 and 2014 were enrolled in this study. According to the CACI, the age-adjusted comorbidity index was calculated by weighting individual comorbidities; CACI4 was considered the low-CACI group, whereas CACI≥4 was considered the high-CACI group. The correlations between the CACI and clinicopathologic features and survival outcomes were statistically analyzed.The patients with a high CACI were more likely to be old and had higher CA19-9 levels and lower incidences of portal vein resection and blood transfusion. The rate of patients who received chemotherapy was significantly higher in the low-CACI group than in the high-CACI group (87% vs. 69%, P 0.0001). The overall survival (OS) rate was significantly higher in the low-CACI group than in the high-CACI group (P = 0.047). Multivariable analysis showed that a high CACI was a predictor of poor survival (P = 0.024). In the high-CACI group, patients with high relative dose intensity (RDI) for postoperative adjuvant chemotherapy had significantly better relapse-free survival (RFS) and OS than those with low RDI (both P 0.0001).The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy in the resected pancreatic cancer.

Background: Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). Methods: Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. Results: Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). Conclusions: The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. BACKGROUND: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. METHODS: Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). RESULTS: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. CONCLUSIONS: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

Introduction 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. Methods 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. Results 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%. Conclusions 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.

The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.

We conducted a prospective multicenter phase II trial of patients with borderline resectable pancreatic carcinoma to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (OS). The clinical trial primarily evaluated OS time from the first day of protocol therapy as a primary endpoint. The secondary endpoints were recurrence-free survival from the first day of protocol therapy, safety of the protocol therapy (adverse effect), morbidity based on the Clavien Dindo classification of more than III, response rate, preoperative/postoperative tumor marker (CA 19-9, CEA), rate of normalization, reduction rate of the maximum standardized uptake value on positron emission tomography-computed tomography (limited to institutions where positron emission tomography-computed tomography was available), chemotherapeutic effect grade based on Evans' classification, resection rate, R0 resection rate, surgical data (operative time, blood loss, transfusion, postoperative hospital day), overall morbidity rates (reoperation, rate of readmission, mortality), patient rate in postoperative adjuvant therapy (entry rate, completion rate), dose intensity, quality of life regarding fatigue and malaise assessed by the questionnaire of FACIT-F (Japanese version), and peripheral sensory neuropathy assessed by the questionnaire of the FACT/GOG-NTX subscale (version 4; Japanese version). Sixty patients were included in the study, and 18 leading Japanese institutions and hospitals (all high-volume centers in pancreatic surgery) participated in this trial.

Background/aim This retrospective study focused on the correlation between molecular markers and prognostic outcomes of colon cancer patients depending on sidedness. Materials and methods A total of 117 stage I-III colon cancer patients who underwent colectomy were enrolled. Novel methylation markers (KIF1A, PAX5 and VGF) were selected for epigenetic evaluation and p53 and ERCC1 protein expression was examined for the investigation of genetic alterations. Results High frequency of methylation was observed in 68.2% of right-sided and 39.7% of left-sided colon cancer cases (p=0.004). Abnormal p53 was identified in 52.3% of right-sided and 75.3% of left-sided cases (p=0.015). In right-sided cases, highly methylated genes demonstrated significantly favorable disease-free survival (p=0.049). Regarding left-sided cases, advanced T stage (p=0.028) and abnormal p53 (p=0.028) were revealed to be significant predictive factors of the disease-free survival outcome. Conclusion Molecular alterations, as significant prognostic factors, might differ depending on the sidedness of colon cancers.

There are only a limited number of comprehensive reports for retroperitoneal tumors (RPTs). The aim of this study was to perform an interdepartmental data collection for RPTs and to comprehensively clarify the clinical characteristics of this rare disease. All patients who were diagnosed with RPT from January 2005 to July 2018 in a single institution were included. The analyzed factors included demographics, clinical features, treatment methods, pathological diagnosis, and prognosis. A total of 422 patients (215 males and 207 females) with primary RPTs were identified. Biopsy for RPT was performed in 180 patients (43%). Among the 422 patients, 239 (57%) underwent surgery. The most common tissue origin was mesodermal (n = 99, 41%), followed by neurogenic (n = 54, 23%), extragonadal (n = 27, 11%), and metastatic tumors (n = 13, 5%). Among the 99 resected mesodermal tumors, the most common pathological subtypes were liposarcoma (n = 55, 56%) and leiomyosarcoma (n = 16, 16%). The long-term outcomes after surgery were analyzed in patients with intermediate and malignant sarcomas (including liposarcoma, leiomyosarcoma, and others combined, n = 71). The 3- and 5-year disease-free survival rates in the intermediate tumors were 68.2% and 54.2%, respectively, whereas those in the malignant tumors were 48.6% and 28.9%, respectively. The 3- and 5-year overall survival rates in the intermediate tumors were 100% and 94.1%, respectively, whereas those in the malignant tumors were 78.4% and 72.8%, respectively (p = 0.009). The clinical manifestations of RPTs were extremely variable. Recurrence after repeating resection is commonly observed in patients with malignant retroperitoneal sarcoma.

Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.

Background Gastric cancer (GC) exhibits heterogeneous clinical and molecular features, requiring the development of new biomarkers to further understand this disease. Our transcriptomic analysis detected overexpression of melanoma-associated antigen A6 (MAGEA6) in metastatic GC, leading us to determine the clinical significance of MAGEA6 in GC. Materials and methods Fourteen GC cell lines and 230 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. Polymerase chain reaction array analysis was performed to identify coordinately expressed cancer-related genes, and immunohistochemistry (IHC) was used to detected MAGEA6 expression in situ. Results MAGEA6 mRNA levels were positively correlated with the expression of matrix metallopeptidase 9 mRNA. MAGEA6 mRNA levels were higher in GC tissues compared with those in normal adjacent tissues. Patients with high MAGEA6 expression had significantly worse prognosis. MAGEA6 protein levels in primary lesions predicted the likelihood of recurrence. Conclusion Overexpression of MAGEA6 in GC tissues represents a promising biomarker for assessing the malignant phenotype of GC.

This study aimed to explore the impact of serum tumor markers on survival for patients with pancreatic cancer (PC) who received initial systemic therapy (IST) followed by surgery. Between April 2010 and July 2018, 285 consecutive patients who underwent curative intent surgery for PC were enrolled in the study. The relation between carbohydrate antigen 19-9 and duke pancreatic monoclonal antigen type 2 (DUPAN-2) after IST was analyzed as well as PC prognosis. The study identified 95 patients who underwent systemic chemotherapy with or without radiotherapy as IST from the our prospectively maintained database at the Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. Survival analysis of the 95 patients showed significant differences in recurrence-free survival (RFS) and overall survival (OS) between the DUPAN-2-normalized (D-normalized) and DUPAN-2-unnormalized (D-unnormalized) groups (median RFS, 24.1 vs. 14.2 months, p = 0.003; median OS, not reached vs. 29.6 months, p = 0.003). In addition, a tendency of differences in survival was observed between the D-normalized and D-unnormalized groups with borderline resectable PC (RFS, 20.1 vs. 14.2 months, p = 0.052; OS, not reached vs. 29.6 months, p = 0.081), and significant differences in survival were observed between the D-normalized and D-unnormalized groups with unresectable PC (RFS, 25.1 vs. 12.1 months, p

Inflammation plays a critical role in the development and progression of cancers. We evaluated the clinical significance of the preoperative modified systemic inflammation score (mSIS) to predict long-term outcomes of patients with esophageal squamous cell carcinoma (ESCC). We included 443 patients who underwent curative resection of ESCC. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte-to-monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0 g/dL and LMR ≥ 3.4), mSIS 1 (ALB

Postoperative pancreatic fistula (POPF) is the most threatening complication after pancreatectomy. This study aimed to directly assess pancreatic fatty infiltration with preoperative computed tomography (CT) imaging and to investigate whether a preoperative analysis of patient variables, including CT characteristics and clinical factors, can predict POPF. We enrolled 150 consecutive patients who underwent curative pancreatectomy. Radiographic factors, including pancreatic fat volume, were measured using preoperative CT imaging and the predictive factors were explored using univariate and multivariate analyses. POPF developed in 30 patients (20.0%). The ratio of pancreatic fat (RPF) ≥ 4.83% was associated with a risk of POPF, high body mass index (BMI), and obese body habitus. Patients with POPF were significantly more likely to have high BMI (≥ 25 kg/m2), obese body habitus, and an RPF ≥ 4.83% than patients without POPF. In the multivariate analysis, visceral fat area/skeletal muscle index (VFA/SMI) ≥ 1.94 (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.43–12.9, p = 0.0095) was the sole independent predictive factor for POPF. For patients with a soft pancreas, VFA/SMI ≥ 1.94 (OR 5.67, 95% CI 2.05–15.7, p = 0.0008) was again the sole independent predictive factor for POPF. Preoperative CT images can examine pancreatic fatty infiltration, and patients who had POPF were significantly associated with a high RPF. Among several parameters, VFA/SMI was the only independent predictive factor for clinically relevant POPF. Preoperative evaluation of these body composition variables and the pancreatic configuration could be useful for predicting POPF.

BACKGROUND We analyzed the clinical impact of chemotherapy or chemoradiotherapy as initial treatment (IT), focusing on treatment duration, on morbidity and mortality in patients with resected pancreatic ductal adenocarcinoma. METHODS We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for

Aim This study aimed to assess the clinical utility of preoperative evaluation of liver fibrosis using platelet-albumin-bilirubin (PALBI) grade, Fibrosis-4 index (FIB-4), and aspartate transaminase-to-platelet ratio index (APRI) for hepatocellular carcinoma (HCC) patients and explore the clinical impact of these models with regard to perioperative risks and HCC prognosis. Methods Between January 2003 and December 2018, 305 consecutive patients who underwent hepatectomy for HCC were enrolled. Results The APRI showed the most robust diagnostic performance through each fibrosis stage among three models (PALBI, FIB-4, and APRI): fibrosis stage 3 (f3), area under the curve [AUC] = 0.55, 0.72, and 0.76; and f4, AUC = 0.51, 0.71, and 0.76, respectively). In addition, survival analysis revealed that all three models were significantly associated with HCC prognosis. PALBI (grade 1 vs. 2, 3): recurrence-free survival (RFS): median survival time (MST), 34 vs. 17 months, 0.007; overall survival (OS): MST, 115 vs. 68, 0.02. FIB-4 (grade 1, 2 vs. 3): RFS: MST, 34 vs. 22, 0.004, OS: MST, 120 vs. 63, 0.0001. APRI (grade 1, 2 vs. 3), RFS: MST, 30 vs. 20, 0.0005; OS: MST, 107 vs. 55, 0.0003. Among three scoring systems, only PALBI grade was significantly associated with both operative time (median, 303 vs. 340 min, 0.01) and intraoperative blood loss (median, 581 vs. 859 mL, 0.03). Conclusions This study showed robust performances of selected liver reserve and fibrosis models to predict HCC prognosis. Of them, PALBI might be used for assessing perioperative risks for hepatectomy for HCC.

Patients undergoing subtotal esophagectomy for esophageal cancer frequently experience postoperative pneumonia. Development of preoperatively determined predictors for postoperative pneumonia will facilitate identifying high-risk patients and will assist with informing patients about their risk of postoperative pneumonia, enabling physicians to estimate with greater accuracy, will result in tailoring perioperative management. Postoperative pneumonia was defined according to the revised Uniform Pneumonia Score. We analyzed the data for 355 patients to compare 32 potential predictive variables associated with postoperative pneumonia after subtotal esophagectomy. Forty-one patients (11.5%) had postoperative pneumonia. Preoperative cholinesterase (ChE) concentrations demonstrated the greatest area under the curve value (0.662) to predict postoperative pneumonia (optimal cutoff value = 217 IU/l). Univariate analysis identified a continuous value of preoperative ChE concentration as a significant risk factor for postoperative pneumonia (P = 0.0014). Multivariable analysis using factors potentially relevant to pneumonia revealed that preoperative ChE concentration was one of independent risk factors for pneumonia after esophagectomy (P = 0.008). Patients with low ChE concentrations were at increased risk of postoperative pneumonia in most patient subgroups. Moreover, the odds ratios of low ChE concentrations were highest in patients undergoing neoadjuvant treatment. A combination of preoperative serum ChE concentrations and Brinkman index stratified patients into low, intermediate, and high risk of postoperative pneumonia. Our findings indicate that preoperative ChE concentrations, particularly in combination with Brinkman index, may serve simply as a determined predictor of pneumonia after subtotal esophagectomy and may facilitate physicians’ efforts to reduce the incidence of postoperative pneumonia.

Although peritoneal lavage cytology often serves as a sensitive method to detect free cancer cells in the abdominal cavity, some patients experience peritoneal recurrence despite negative cytology. The aim of this study was to evaluate mRNAs in peritoneal lavage fluid as potential markers for predicting the peritoneal recurrence of gastric cancer (GC). Peritoneal lavage fluid samples were obtained during surgery conducted on 187 patients with GC and from 30 patients with non-malignant disease (controls). The mRNA levels of nine candidate markers were quantified, and analysis of a receiver-operating characteristic curve compared their accuracies. The cutoff was defined as the highest value of the controls. Synaptotagmin XIII (SYT13) and carcinoembryonic antigen (CEA) mRNA levels were analyzed further. SYT13 levels were significantly associated with shorter peritoneal recurrence-free survival (PRFS) and overall survival. Among patients with negative peritoneal lavage cytology, those positive for either SYT13 or CEA mRNA experienced significantly shorter peritoneal recurrence-free survival compared with those with negative fluid (hazards ratio [HR] 4.21, P = 0.0114; HR 3.53; P = 0.0426, respectively). Univariate analysis revealed that SYT13 and CEA mRNA levels were significant predictors of peritoneal recurrence. Positive levels of both SYT13 and CEA mRNA demonstrated the highest HR for peritoneal recurrence (HR 12.27, P = 0.0064). Multivariable analysis revealed that SYT13 positivity was a significant independent prognostic factor (HR 3.69; 95% confidence interval, 1.18–12.74; P = 0.0246). Combined measurement of SYT13 and CEA mRNA levels in peritoneal lavage fluid could serve as a promising approach to predict peritoneal recurrence of GC.