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BackgroundAberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored.MethodsWe evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression.ResultsCD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers.ConclusionsCD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.

Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Although drug development over the past decade has gradually improved the prognosis of PDAC, the prognosis remains extremely poor. The predominant determinant of a poor prognosis is that patients are already at the advanced stage when they are diagnosed. Therefore, it is essential to detect early‐stage PDAC to ensure a good prognosis. However, in general, being asymptomatic at the early stage makes the detection of early‐stage PDAC very difficult. Recently, much attention has been focused on the utility of a liquid biopsy as a biomarker. Theoretically, early‐stage tumors can be detected even under asymptomatic conditions. A number of studies on liquid biopsies have been reported so far. Several biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCS), and exosomes, are used in liquid biopsies, with the potential to be applied to the clinical setting. Each biomarker is reported to have different utilities, such as the detection of early‐stage disease, the differential diagnosis of PDAC from other types of pancreatic tumors, the prediction of the prognosis or risk of recurrence, and monitoring the treatment response. In this review, we focus on ctDNA, CTCS, and exosomes as representative liquid biopsy biomarkers and describe the specific functions of each biomarker in the treatment of PDAC. Furthermore, we discuss the application of liquid biopsies, especially for the surgical management of PDAC., Much attention has been focused on the utility of a liquid biopsy as a biomarker. We focus on ctDNA, CTCS, and exosomes as representative liquid biopsy biomarkers and describe the specific functions of each biomarker in the treatment of PDAC. Furthermore, we discuss the application of liquid biopsies, especially for the surgical management of PDAC.

Although the prognosis of recurrent pancreatic cancer (RPC) is improving with the appearance of new anticancer drugs, prognostic indicators for RPC are still poorly understood. The aim of this study was to evaluate significance of the inflammation-based prognostic score, including modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and Prognostic Nutritional Index (PNI), in patients with RPC.This study reviewed 263 patients of pancreatic ductal adenocarcinoma at our institution between 2006 and 2015. A receiver operating characteristics curve analysis was performed to determine the cut-off values. The prognostic significance of the inflammation-based prognostic scores were evaluated by a multivariate analysis.172 patients (65.4%) who had recurrence was included in this study. The optimal PNI for predicting 1-year survival after recurrence was 40 with higher area under receiver operating characteristics curve value (0.704) in comparison with other inflammation-based prognostic scores. A univariate and multivariate analysis revealed that liver metastasis (P 0.001) and PNI 40 (P 0.001) were independently associated with the survival time after recurrence. When each of the two predictors was counted as one point and the points were calculated for all cases, a good stratified survival curve was obtained, showing the shorter survival in the higher points: median survival times of 2, 1, and 0 points were 4.3, 11.1, and 21.2 months, respectively (P 0.001).Inflammation-based prognostic scores, especially PNI is useful clinical biomarker for predicting the survival time after recurrence in patients with pancreatic adenocarcinoma.

Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical T1 stage pancreatic cancer. Methods: Data from two centers were included in the comparative analysis, with overall and recurrence-free survival as primary outcomes, between January 2010 and December 2017. Results: In total, 45 patients were retrospectively reviewed in this study. Two patients in the neoadjuvant group were excluded because of distant metastasis during neoadjuvant treatment. Finally, 43 patients underwent a pancreatectomy for clinical T1 pancreatic cancer, of whom, 35 and 8 patients underwent upfront surgery and neoadjuvant treatment, respectively. Overall survival was similar in the two study groups (5-year overall survival rate: neoadjuvant group, 75%, upfront surgery group, 43.9%, p = 0.066). Conclusions: In our study on patients with clinical T1 stage pancreatic cancer, no significant differences were reported in the oncological outcome in the neoadjuvant therapy group. Large-scale prospective studies are needed to determine the survival benefits of neoadjuvant treatment for early-stage pancreatic cancer.

Background & Aims Pancreatic ductal adenocarcinomas (PDACs) frequently metastasize to the lymph nodes; strategies are needed to identify patients at highest risk for lymph node metastases. We performed genome-wide expression profile analyses of PDAC specimens, collected during surgery or endoscopic ultrasound–guided fine-need aspiration (EUS-FNA), to identify a microRNA (miRNA) signature associated with metastasis to lymph nodes. Methods For biomarker discovery, we analyzed miRNA expression profiles of primary pancreatic tumors from 3 public data sets (The Cancer Genome Atlas, GSE24279, and GSE32688). We then analyzed 157 PDAC specimens (83 from patients with lymph node metastases and 74 without) from Japan, collected from 2001 through 2017, for the training cohort and 107 PDAC specimens (63 from patients with lymph node metastases and 44 without) from a different medical center in Japan, from 2002 through 2016, for the validation cohort. We also analyzed samples collected by EUS-FNA before surgery from 47 patients (22 patients with lymph node metastases and 25 without; 17 for the training cohort and 30 from the validation cohort) and 62 specimens before any treatment from patients who received neoadjuvant chemotherapy (9 patients with lymph node metastasis and 53 without) for additional validation. Multivariate logistic regression analyses were used to evaluate the statistical differences in miRNA expression between patients with vs without metastases. Results We identified an miRNA expression pattern associated with diagnosis of PDAC metastasis to lymph nodes. Using logistic regression analysis, we optimized and trained a 6-miRNA risk prediction model for the training cohort; this model discriminated patients with vs without lymph node metastases with an area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.77–0.89). In the validation cohort, the model identified patients with vs without lymph node metastases with an AUC of 0.73 (95% CI, 0.64–0.81). In EUS-FNA biopsy samples, the model identified patients with vs without lymph node metastases with an AUC of 0.78 (95% CI, 0.63–0.89). The miRNA expression pattern was an independent predictor of PDAC metastasis to lymph nodes in the validation cohort (odds ratio, 17.05; 95% CI, 2.43–119.57) and in the EUS-FNA cohort (95% CI, 0.65–0.87). Conclusions Using data and tumor samples from 3 independent cohorts, we identified an miRNA signature that identifies patients at risk for PDAC metastasis to lymph nodes. The signature has similar levels of accuracy in the analysis of resected tumor specimens and EUS-FNA biopsy specimens. This model might be used to select treatment and management strategies for patients with PDAC.

Recent advances in multidisciplinary treatments are improving the postoperative prognosis of pancreatic ductal adenocarcinoma (PDAC). However, the prognosis even after potentially curative resection remains poor. The aim of this study was to identify the clinical and pathological features of actual 5-year survivors under current circumstances. A total of 128 patients who underwent pancreatectomy for PDAC at our institution between January 2006 and December 2011 were retrospectively analyzed. The actual 5-year overall survival rate for all patients was 30.9%, with a median survival time of 33.1 months. Of 128 patients, 25 (19.5%) survived for 5 years after surgery without disease recurrence. A univariate analysis showed that the pretreatment serum CA19–9 value, tumor depth, lymph node metastasis, and UICC stage at resection were significant predictive factors for the actual long-term survival. A multivariate analysis showed that a pretreatment serum CA19–9 value ≥ 110 U/mL was a significant unfavorable prognostic indicator. In addition, all subjects in the 5-year survival group completed adjuvant chemotherapy. The recurrence rate in the liver was significantly lower and that in the lung significantly higher in the long-term survival group than in the short-term survival group. The factors contributing to the long-term survival of PDAC were the pretreatment CA19–9 value and the completion of adjuvant chemotherapy. To achieve the actual long-term survival and cure after pancreatectomy for pancreatic cancer, further treatment strategies enhancing the completion rate of adjuvant chemotherapy are required.

Objective: The study objective is to investigate the impact of unilateral nephrectomy on the complications after pancreatoduodenectomy (PD). Summary of background data: Preoperative renal insufficiency is a risk factor for postoperative complications and mortality after various types of surgery. However, the specific postoperative risks in uninephrectomized (UN) patients are largely unknown. Methods: Between January 2010 and June 2014, a total of 177 patients underwent PD at the Department of Surgery, Nara Medical University. Among them, 7 patients (4.0%) were UN. We retrospectively evaluated the influence of the UN status on the postoperative complications. Results: The rate of acute kidney injury in the UN group was significantly higher than that in the control group (28.6% versus 1.2%; P = 0.017). In addition, the rates of surgical site infection of the organ/space (57.1% versus 9.0%; P = 0.006) and sepsis (42.9% versus 3.5%; P = 0.003) in UN group were significantly higher. Even on a reanalysis of only patients with soft pancreas, the significance remained. Conclusions: The UN status has a significant impact on the rate of morbidities, such as acute kidney injury and various infectious complications, including surgical site infections of organ/space, sepsis, and cholangitis after PD. Appropriate intervention should be implemented to decrease the morbidity rate for UN patients.

A 28-year-old woman who was 34 weeks pregnant was admitted with complaints of cough and blood-stained sputum. After delivery of the baby at 37 weeks gestation, computed tomography and magnetic resonance imaging revealed a tumor in the right lung and a 15-mm brain metastasis. A diagnosis of lung adenocarcinoma was made, cT4N3M1b (stage IV disease) by pleural fluid cytology. Additional testing for anaplastic lymphoma kinase (ALK) fusion protein showed a strongly positive result, which was then confirmed by fluorescence in situ hybridization. The patient was started on treatment with alectinib, and the tumor and brain metastasis had almost vanished by 2 months after the start of this treatment. In the literature, there are 59 reports of lung cancer diagnosed during pregnancy, including two cases of cancer with expression of ALK fusion protein and five cases showing epidermal growth factor receptor mutation. The type of mutation should be taken into consideration while selecting for the appropriate therapeutic strategy.

There is no clear evidence that preoperative chemotherapy for resectable colorectal liver metastasis (CRLM) is superior to up-front surgery (UFS). The aim of this study was to identify the risk factors associated with poor prognosis after UFS for CRLM. Data about consecutive patients with CRLM who underwent liver resection at Nara Medical University Hospital between January 2000 and December 2015 were retrieved from a prospective database. Recurrence that developed within 2 years after liver resection and could not be surgically resected was defined as unresectable recurrence (UR). Preoperative risk factors associated with UR after UFS were analyzed. Among the patients with the identified risk factors, the patients who were treated with UFS were compared with those who received preoperative chemotherapy via propensity score-matching analysis. There were 167 patients treated with UFS, and 71 of them developed UR (the UR group). The overall survival (OS) rate of the UR group was significantly worse than that of the non-UR group (5-year survival rate: 3.8 vs. 66.8%, p

BACKGROUND The association between bacterial infection and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD) has not been fully elucidated. METHODS Microbiological data for intraoperative bile culture (BC) and drain culture on postoperative day 4 (DC) were collected. The study population was classified into the following three groups: P1 (positive BC and DC), P2 (positive BC and negative DC), and N (negative BC). A total of 209 patients (P1: 38, P2: 72, and N: 99) who underwent PD between May 2013 and May 2018 met the inclusion criteria of the study. RESULTS The rate of CR-POPF was significantly higher in the P1 group (34.2%) than in the P2 (12.5%; P = .007) and N groups (14.1%; P = .008). Between P1 and P2 groups, a significant difference was observed in the proportion of Enterococcus faecalis grown in BC (42.1% vs 4.2%; P

Background Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a is a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted a two-step, phase I, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of DS-8895a in patients with advanced solid tumors. Methods Step 1 was a dose escalation cohort in advanced solid tumor patients (six dose levels, 0.1–20 mg/kg) to determine Step 2 dosing. Step 2 was a dose expansion cohort in EPHA2-positive esophageal and gastric cancer patients. DS-8895a was intravenously administered every 2 weeks for the duration of the study, with a 28-day period to assess dose-limiting toxicity (DLT). Safety, pharmacokinetics, tumor response, and potential biomarkers were evaluated. Results Thirty-seven patients (Step 1: 22, Step 2: 15 [9: gastric cancer, 6: esophageal cancer]) were enrolled. Although one DLT (Grade 4 platelet count decreased) was observed in Step 1 (dose level 6, 20 mg/kg), the maximum tolerated dose was not reached; the highest dose (20 mg/kg) was used in Step 2. Of the 37 patients, 24 (64.9%) experienced drug-related adverse events (AEs) including three (8.1%) with Grade ≥ 3 AEs. Infusion-related reactions occurred in 19 patients (51.4%) but were manageable. All patients discontinued the study (evident disease progression, 33; AEs, 4). Maximum and trough serum DS-8895a concentrations increased dose-dependently. One gastric cancer patient achieved partial response and 13 patients achieved stable disease. Serum inflammatory cytokines transiently increased at completion of and 4 h after the start of DS-8895a administration. The proportion of CD16-positive natural killer (NK) cells (CD3−CD56+CD16+) decreased 4 h after the start of DS-8895a administration, and the ratio of CD3−CD56+CD137+ to CD3−CD56+CD16+ cells increased on day 3. Conclusions Twenty mg/kg DS-8895a infused intravenously every 2 weeks was generally safe and well tolerated in patients (n = 21) with advanced solid tumors. The exposure of DS-8895a seemed to increase dose-dependently and induce activated NK cells. Trial registration Phase 1 Study of DS-8895a in patients with advanced solid tumors (NCT02004717; 7 November 2013 to 2 February 2017); retrospectively registered on 9 December 2013. Electronic supplementary material The online version of this article (10.1186/s40425-019-0679-9) contains supplementary material, which is available to authorized users.

A 46-year-old woman with severe skin sarcoidosis, mainly on the back of the trunk, persisting for >15 years, was followed up without systemic treatment. In 2014, she was started on minocycline monotherapy owing to worsening of the skin sarcoid lesions. Surprisingly, after approximately 1 year of the monotherapy, nearly all skin lesions resolved with only light residual scars, despite the poor efficacy of the monotherapy for pulmonary sarcoidosis. The patient's serum angiotensin-converting enzyme levels also decreased to the normal range. The presence of Propionibacterium acnes was confirmed when a retrospectively immunostained epithelioid granuloma, obtained from skin biopsy, demonstrated staining with monoclonal antibodies specific for P. acnes. Minocycline monotherapy, thus, appears to be a possible treatment modality for skin sarcoidosis.

Pancreatic cancer is a major cause of cancer-associated mortality. In recent years, improvement of chemotherapy provided better prognosis for the patient with both resectable and unresectable pancreatic cancer. This review discusses new perspective in all aspects of treatment for pancreatic cancer.

Late-onset gastrointestinal hemorrhage after pancreatoduodenectomy (PD) occasionally occurs repeatedly or leads to a serious condition. This retrospective study aimed to clarify its frequency and pathogenesis. A total of 147 consecutive patients who underwent PD for pancreatic cancer between 2006 and 2014 were evaluated. Patients were divided into two groups according to the occurrence of late-onset gastrointestinal hemorrhage on postoperative day 100 or later. Furthermore, recurrence and portal vein (PV) hemodynamics were thoroughly reevaluated by computed tomography. Eleven patients experienced late-onset gastrointestinal hemorrhage. The bleeding sites were gastrojejunostomy in four patients, choledochojejunostomy in two, transverse colic marginal vein in one, and unknown in four. The median occurrence time of late-onset gastrointestinal hemorrhage was 13.3 months after PD. PV occlusion (63.6 vs. 8.9%; p

Background Eribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia—specifically, organized pneumonia—during treatment with eribulin in a patient with advanced breast cancer. Case presentation A 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report. She had received eribulin as third-line chemotherapy. Five days after her second treatment with eribulin, she was admitted to our hospital with dyspnea and dry cough. Upon admission, a chest computed tomography scan showed consolidation, with air bronchograms along the bronchovascular bundle of both lower lobes. The patient’s serum levels of sialylated carbohydrate antigen Krebs von den Lungen-6 were high, as were her surfactant protein-D levels. There was no evidence of heart failure, renal failure, or infection. Based on the clinical cause, as well as on the findings of organized pneumonia, the patient was diagnosed as having interstitial pneumonia and treated with corticosteroids. After the initiation of steroid treatment, her respiratory condition and chest radiological findings improved. Conclusions This case reveals an association between eribulin treatment and interstitial pneumonia. To our knowledge, this is the first case report to describe eribulin-induced organized pneumonia. Clinicians should be aware that interstitial pneumonia can develop during treatment with anti-cancer agents.

It is unclear whether anatomic resection achieves better outcomes than nonanatomic resection in patients with hepatocellular carcinoma. This study aimed to compare the outcomes of anatomic resection and nonanatomic resection for hepatocellular carcinoma located on the liver surface via one-to-one propensity score-matching analysis.Data from all consecutive patients who underwent liver resection for primary solitary hepatocellular carcinoma at Nara Medical University Hospital, Japan, January 2007- December 2015 were retrieved. Superficial hepatocellular carcinomas were defined as hepatocellular carcinoma that extended to a depth of 3 cm from the liver surface and measured 5 cm in diameter. The prognoses of the patients with superficial hepatocellular carcinoma who underwent anatomic resection and nonanatomic resection were compared.In this study 23 patients with superficial hepatocellular carcinoma underwent anatomic resection and 70 patients who underwent nonanatomic resection. The recurrence-free survival rate of the patients who underwent anatomic resection was better than that of the patients who underwent nonanatomic resection (P = .006), while no such difference was observed for nonsuperficial hepatocellular carcinoma. After the propensity score-matching procedure, the resected liver volume and operation time were the only background or clinical characteristics to exhibit significant differences between the anatomic resection (n = 20) and nonanatomic resection groups (n = 20). The recurrence-free survivial rate of the patients who underwent anatomic resection was significantly than that of the patients that underwent nonanatomic resections (P = .030), but overall survival did not differ significantly between the groups (P = .182).Anatomic resection decreases the risk of tumor recurrence and improves recurrence-free survival compared with nonanatomic resection in patients with superficial hepatocellular carcinoma.

Background Interstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA. Methods Between April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA. Results Thirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA. Conclusions This is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to determine the risk factors for ILD-AA in advanced lung cancer patients. ΔSP-D might be a serum prognostic biomarker of ILD-AA. Clinicians should evaluate serum SP-D during chemotherapy and should carefully monitor the clinical course in patients with high ΔSP-D.

A femoral hernia is a relatively rare condition, and no standard surgical methods have so far been established. In this study, we investigated the development of a femoral hernia after inguinal herniorrhaphy. A total of 1,969 patients who underwent surgery for an inguinal hernia from April 1992 to March 2012 were enrolled in this study. The patients were composed of 1,934 (98.2 %) inguinal hernia and 35 (1.8 %) femoral hernia patients. Of these, we retrospectively studied the femoral hernia cases with reference to the use of inguinal herniorrhaphy. Of all 35 femoral hernia cases, six cases (17.1 %) were femoral type recurrences after inguinal herniorrhaphy performed by the conventional or mesh plug methods. The surgical methods used for the 35 cases were mesh plug repair in 15 cases (42.9 %), the Kugel patch method in seven (20.0 %) and conventional repair in 13 patients (37.2 %). Inguinal type recurrences developed in three cases (8.6 %) that were re-repaired by mesh plug repair or sac resection. There were no femoral or inguinal type recurrences after Kugel patch repair for a femoral hernia. The results of this study suggested the importance of repairing all hernia orifices when repairing a groin hernia. The Kugel patch repair method is available for all inguinal region hernias by the same approach, and it seems to be useful for preventing the development of recurrence after surgery.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains the fourth leading cause of cancer-related deaths in the United States, and the incidence of this disease continues to rise. Although recent advances in treatment modalities for this malignancy has somewhat improved patient outcomes in the recent years, the overall prognosis of patients with PDAC remains dismal. From a biological viewpoint, while the G-protein-coupled receptor (GPCRs) proteins play a multitude of important functions in tumor pathogenesis, their clinical significance if any in human cancers, especially PDAC, remains unclear. Herein we aimed to perform a comprehensive profiling of all GPCRs, in an attempt to identify the most critical protein(s) that have important biological and clinical significance in PDAC. Methods: This study included systematic analysis of 796 PDAC patients, which included data analysis from 331 patients from public datasets (TCGA, ICGC and GSE57495) and 465 patients from two, independent, clinical patient cohorts. Computational and bioinformatic analysis of genomewide expression profiling datasets led to the selection of candidate GPCR genes during the discovery and validation steps. The clinical significance of candidate genes were subsequently investigated in two in-house patient cohorts (training cohort: n = 321, validation cohort: n = 144) using qRT-PCR assays. The data were analyzed by performing appropriate statistical analyses to determine patient prognosis. Finally, using a series of functional studies, we confirmed the biological function of the candidate GPCRs in PDAC. Results: Analysis of all 33 GPCRs, led to the identification of GPR115, as the only significantly up-regulated candidate, with a prognostic significance in all three public datasets (P=0.02, 0.04 and 0.05, respectively). The patients with high-GPR115 expression exhibited significantly poorer postoperative prognosis for OS and RFS, in two, large, independent clinical cohorts (training cohort: P Conclusion: We for the first time have identified GPR115 as a key GPCR with important prognostic significance, as well as functional role in tumor progression; providing a rationale that this may be a potential target for therapeutic targeting in patients with PDAC. Citation Format: Satoshi Nishiwada, Tadanobu Shimura, Kensuke Yamamura, Fuminori Sonohara, Takahiro Akahori, Kota Nakamura, Naoya Ikeda, Yasuhiro Kodera, Masayuki Sho, Ajay Goel. Identification of GPR115 as a key G-protein coupled receptor as a key prognostic and therapeutic target in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4935.

343 Background: The efficacy of neoadjuvant treatment for pancreatic cancer (PC) remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiothrapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred eighty one patients who preoperatively received full-dose gemcitabine (1000mg/m2) with concurrent radiation of 54 Gy between 2006 and 2017 were analyzed. One hundred forty nine patients who proposed upfront surgery were served as control. Results: Among the 181 patients treated with NACRT, 23 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 10, tumor progression in 7 and poor PS in 6. While among the 149 patients who proposed upfront surgery, 10 (7%) couldn’t undergo pancreatic resection at laparotomy, because of distant metastasis in 8 and tumor progression in 2. In overall survival analysis of all patients with resected and unresected tumor, patients treated with NACRT had a better prognosis than those without (median survival time: 37.0 vs. 27.1M, P = 0.049). According to tumor resectability status including R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) PC, in the R and BR-P group, overall survival was significantly better in the patients with NACRT (45.7 vs. 33.8M, P = 0.049, 61.7 vs. 14.6M, P = 0.002). Also only for resected tumors, patients treated with NACRT had a better prognosis than those without in the R and BR-P group (53 vs. 36.5M, P = 0.033, 61.7 vs. 14.6M, P = 0.002), while NACRT had no significant impact on prognosis in the BR-A group. The rate of pancreatic fistula, delayed gastric emptying and abdominal abscess were lower in the NACRT group than the control group. Furthermore, the lymph node metastasis rate, R0 resection rate and pathological stage were favorable in the NACRT group (P < 0.001, P = 0.005, P < 0.001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.001). Conclusions: NACRT had a variety of favorable impact in PC treatment. In particular, it significantly improved the prognosis in the R and BR-P, but not BR-A.

Lessons Learned The triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic ductal adenocarcinoma was an effective treatment that appeared to be better tolerated than the widely used FOLFIRINOX regimen. SOXIRI regimen may provide an alternative approach for advanced pancreatic cancer. Background In our previous phase I study, we determined the recommended dose of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). This phase II study was conducted to assess the safety and clinical efficacy in patients with unresectable PDAC. Methods Patients with previously untreated metastatic and locally advanced PDAC were enrolled. The primary endpoint was response rate (RR). Secondary endpoints were adverse events (AEs), progression-free survival (PFS), and overall survival (OS). Patients received 80 mg/m2 of S-1 twice a day for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results Thirty-five enrolled patients received a median of six (range: 2–15) treatment cycles. The RR was 22.8% (95% confidence interval [CI]: 10.4–40.1); median OS, 17.7 months (95% CI: 9.8–22.0); and median PFS, 7.4 months (95% CI: 4.2–8.4). Furthermore, the median OS in patients with distant metastasis was 10.1 months, whereas that in patients with locally advanced PDAC was 22.6 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). There were no treatment-related deaths. Conclusion SOXIRI is considered a promising and well-tolerated regimen in patients with unresectable PDAC.

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m2) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P < 0.0001, P = 0.006, P < 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.