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.

In the present study, we investigated the role of lysyl oxidase‑like 2 (LOXL2), the correlation between LOXL2 and epithelial to mesenchymal transition (EMT) and the effects of using β‑aminopropionitrile (BAPN) to inhibit LOXL2 with the aim of reducing tumor progression in hepatocellular carcinoma (HCC). The expression level of LOXL2 was evaluated in HCC and adjacent non‑cancerous tissues using quantitative reverse transcription polymerase chain reaction and clinicopathological analyses. The effects of BAPN on cell proliferation, migration and invasion were investigated in vitro. Additionally, LOXL2 expression was assessed in the culture supernatants of HCC cell lines. Our results revealed that LOXL2 expression was higher in HCC cell lines and tissues. There was a significant correlation between EMT status and LOXL2 levels (P=0.004). BAPN reduced migration and invasion in HCC cells. HCC patients with high levels of LOXL2 expression had relatively shorter disease‑free survival (P=0.009) and overall survival (P=0.035). The expression level of LOXL2 was similar between cell supernatants and HCC cell lines. A multivariate analysis demonstrated that portal vein invasion (P=0.015), venous invasion (P=0.026), serum AFP (α‑fetoprotein) levels (P=0.019) and LOXL2 expression (P=0.009) were independent prognostic factors. Our results indicated that a higher level of LOXL2 may contribute to tumor progression, indicating that LOXL2 has clinical value as a therapeutic target in HCC.

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259 Background: In the past, various prognostic factors in pancreatic ductal carcinoma (PDAC) have been identified, and there found to be not only tumor-specific clinicopathological factors but also individual patient characteristics. In particular, weight loss, muscle wasting and cachexia are hallmarks of PDAC that may be associated with depletion of both skeletal muscle and adipose tissue. Most notably, sarcopenia is defined to be degenerative loss of skeletal muscle mass that is quantifiable using cross sectional imaging computed tomography (CT) by measurement of psoas area and the muscle’s density. Furthermore, visceral adipose tissue loss also has been reported to associate with a poor survival among patients with 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.

RT-PCR. LPA variant binding affinities to LPARs was performed using commercially available cell based LPAR agonist assays. LPAR inhibitors were identified by 3D computational docking of 1.2 million compounds against the active site of the LPA biosynthetic enzyme, autotaxin. LPAR antagonism was determined using commercially available cell based LPAR antagonist assays. Results: LPAR2 and LPAR3 were the main hepatic LPARs. Hepatic LPA2 and LPA3 expression was greater in cirrhotic livers with HCC when compared to livers without HCC. LPAR2 and LPAR3 selectively bound 18:2LPA (RC50 1.6 mM) in preference to other LPA variants (e.g. 20:4LPA RC50 2.4ï -M). Six compounds were identified with LPAR IC50 <10 nM. Conclusion: HCC associated aberrant LPA variant profile is theoretically linked to changes in hepatic LPAR expression and variant specific LPAR binding affinities. LPAR is a potential target to reduce HCC emergence. The six potent LPAR antagonists should be tested in murine models in order to determine effectiveness.

390 Background: Systemic inflammation and nutrition status are considered to influence survival in cancer patients. A variety of systemic inflammation-based prognostic scores have been explored; however, there has been no study to clarify which score could best reflect survival in resected pancreatic cancer patients. Methods: Between 2002 and 2016, 422 consecutive patients who underwent curative resection of pancreatic cancer were enrolled. The Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI) scores for each patients were calculated. Survival of each score was evaluated, and correlations between the score selected on the basis of the prognostic significance and various clinicopathological factors were analyzed. On the other hand, the nutrition markers (pre-albumin, transferrin, and retinol-binding protein) of 30 patients who received the enteral nutrition during the perioperative period were also evaluated. Results: In the analysis of the GPS, the median survival time (MST) was 29.4 months for score 0, 25.5 for score 1, and 17.7 for score 2 ( p< 0.001), and mGPS was also found to be significant ( p= 0.003). On the contrary, there were no significance in MST between other scores (NLR, PLR, PI, or PNI). Multivariate analysis revealed that lymph node metastasis, positive peritoneal washing cytology, and a GPS score of 2 were significant prognostic factors. There was also statistically significant correlation between the GPS score and tumor location (head), tumor size ( > 2.0cm), bile duct invasion, and duodenal invasion. In terms of nutrition status, the postoperative nutrition markers of 30 patients managed by enteral nutrition tended to recover earlier than 79 patients managed by intravenous nutrition. Conclusions: Our results demonstrated that the GPS could be an independent predictive marker and was superior to other inflammation-based prognostic scores in patients with resected pancreatic cancer. The results also suggested that perioperative nutrition support and infection control would improve survival of pancreatic cancer patients.

495 Background: 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. Methods: 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; CACI < 4 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. Results: 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). There was no difference in relapse-free survival (RFS) between the low- and high-CACI groups; however, 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. In the high-CACI group, patients with high relative dose intensity (RDI) for postoperative adjuvant chemotherapy had significantly better RFS and OS than those with low RDI (both P< 0.0001). Conclusions: The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy and could be clinically useful for decision-making in the treatment strategy for pancreatic cancer.

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