Angiogenesis in pancreatic cancer: current research status and clinical implications.

Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.

Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. METHODS: This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). RESULTS: NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. CONCLUSIONS: NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.

Intrinsic Contact Between T and N Classifications in Resected Well-Moderately Differentiated Locoregional Pancreatic Neuroendocrine Neoplasms.

BACKGROUND: The role of N classification is controversial in several prognostication systems proposed for pancreatic neuroendocrine neoplasms (pNENs). The widely accepted modified European Neuroendocrine Tumor Society (mENETS) system suggests this contradiction may be related to T classification. METHODS: Data were collected retrospectively from 981 patients in the Surveillance, Epidemiology, and End Results (SEER) database (1973-2012; cohort 1) and 140 patients from the Pancreatic Cancer Institute of Fudan University (2006-2016; cohort 2). All patients had resected well- to moderately differentiated locoregional pNENs, whereby the mENETS system was adopted. Factors related to N1 classification and the association between N and T classifications were analyzed, and N classification prognosis based on T classification was assessed. RESULTS: In cohorts 1 and 2, tumor size (2-4 cm: p < 0.001 and p = 0.037, respectively; > 4 cm: p < 0.001 and p = 0.012, respectively) and tumors extending beyond the pancreas (p < 0.001 and p = 0.016, respectively), which are factors for T classification, affected N1 classification. For tumors limited to the pancreas, the N1 classification was associated with tumor size (p < 0.001 and p = 0.046, respectively) and predicted poor disease-specific survival (DSS), while for tumors extending beyond the pancreas, the N1 classification did not affect patient outcomes. Findings obtained with data from the SEER database were reproducible with our institutional data. CONCLUSIONS: N classification is associated with T classification, limiting the value of N1 classification for the pNENs tumor-node-metastasis system. A new risk model is necessary to predict patient outcomes and guide clinical practice for the prognosis of pNENs.

Tumor-Infiltrating Platelets Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Platelets are believed to promote tumor growth and metastasis in several tumor types. The prognostic role of blood platelets in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the prognostic value of tumor-infiltrating platelets (TIPs) remains unknown. METHODS: A total of 303 patients who underwent curative pancreatectomy for PDAC were enrolled from two independent centers in China and divided into three cohorts. Paired preoperative blood samples and surgical specimens from all patients were analyzed. The correlations between patient outcomes and preoperative blood platelet counts and the presence of TIPs, respectively, were analyzed. TIPs were identified by immunohistochemical staining of CD42b. Prognostic accuracy was estimated by concordance index (C-index) and Akaike information criterion (AIC). RESULTS: TIPs, but not preoperative blood platelet counts, were associated with overall survival (OS; all P < 0.001) and recurrence-free survival (RFS; all P < 0.001) in the training, testing, and validation sets. Positive CD42b expression predicted poor postsurgical survival. Incorporation of TIPs improved the predictive accuracy of the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for OS in each of the three cohorts (C-index: 0.7164, 0.7569, and 0.7050, respectively; AIC: 472, 386, and 1019, respectively). The new predictor system was validated by incorporating TIPs with the 7th edition AJCC TNM staging system (C-index: 0.7052, 0.7623, and 0.7157; AIC: 476, 386, and 1015). CONCLUSION: TIPs were an independent prognostic factor that could be incorporated into the AJCC TNM staging system to refine risk stratification and predict surgical outcomes of patients with PDAC.

Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma.

OBJECTIVE: To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA. METHODS: The relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection. RESULTS: Adjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P < 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P < 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253-0.510, P < 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387-0.705, P < 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244-0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352-0.847, P = 0.007 for RFS). CONCLUSION: Postoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.

Strategies for pancreatic anastomosis after pancreaticoduodenectomy: What really matters?

BACKGROUND: The postoperative pancreatic fistula rate remains approximately 10-20% even in institutions treating a high-volume of pancreatic cases. The best strategy to restore the continuity between the pancreatic remnant and the digestive tract is still in debate. DATA SOURCES: Studies were identified by searching PubMed for studies published between January 1934 (when pancreaticogastrostomy was technically feasible) and December 2016. The following search terms were used: "duct-to-mucosa", "invagination", "pancreaticojejunostomy", "pancreaticogastrostomy," and "pancreaticoduodenectomy". The search was limited to English publications. RESULTS: Many technical methods have been developed and optimized to restore pancreaticoenteric continuity, including pancreaticojejunostomy, pancreaticogastrostomy, and stented drainage of the pancreatic duct, among other modifications. Researchers have also attempted to decrease the postoperative pancreatic fistula after pancreaticoduodenectomy by using fibrin glue and somatostatin analogues. However, no significant decrease in postoperative pancreatic fistula has been observed in most of these studies, and only an external pancreatic duct stent has been found to decrease the leakage rate of pancreatic anastomosis after pancreaticojejunostomy. CONCLUSION: Pancreatic surgeons should choose a suitable technique according to the characteristics of individual cases.

The clinicopathological and prognostic significance of PD-L1 expression in pancreatic cancer: A meta-analysis.

BACKGROUND: Immunotherapy has shown promise against solid tumors. However, the clinical significance of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This meta-analysis aimed to analyze the prognostic effect of PD-L1 in PDAC. DATA SOURCES: Electronic search of the PubMed, Cochrane Library and Web of Science was performed until December 2016. Through database searches, we identified articles describing the relationship between PD-L1 status and PDAC patient prognosis. Meta-analysis was performed to investigate the relationship between PD-1 and overall survival (OS). RESULTS: Nine studies with 989 PDAC patients were included for PD-L1 expression analysis. And 5 studies with 688 PDAC patients were included in the prognostic analysis. The PD-L1 positive rate measured by immunohistochemistry (IHC) was higher than that measured by polymerase chain reaction (PCR) (P < 0.001). PDAC patients with high expression levels of PD-L1 had significantly reduced OS (HR = 2.34; 95% CI: 1.78-3.08). Subgroup analysis showed that the prognostic effect of PD-L1 levels was similar between the IHC and PCR methods. The PD-L1 positive rate was associated with PDAC T stages; the PD-L1 positive rate in the T3-4 group was higher than that in the T1-2 group (OR = 0.37; P = 0.001). CONCLUSIONS: High PD-L1 expression levels predicted a poor prognosis in PDAC patients. Thus, PD-L1 status helps determine treatment in PDAC patients.

Epithelial-mesenchymal transition in pancreatic cancer: Is it a clinically significant factor?

Pancreatic cancer is one of the most aggressive solid malignancies. This aggressiveness is partly attributable to extensive local tumor invasion and early systemic dissemination as well as resistance to chemotherapy. Epithelial-mesenchymal transition (EMT) plays fundamental roles in embryonic development and in the differentiation of normal tissues and organs. EMT also plays critical roles in tumor formation, dissemination and drug resistance in pancreatic cancer. Emerging data suggest that inhibiting EMT may reverse the EMT phenotype and enhance the efficacy of chemotherapeutic agents against pancreatic cancer cells. Thus, an understanding of the molecular biology of EMT in pancreatic cancer may provide insights into the mechanisms of tumor invasion and metastatic progression and facilitate the development of alternative therapeutic approaches to improve the treatment outcomes for patients suffering from pancreatic cancer.

Effect of the number of positive lymph nodes and lymph node ratio on prognosis of patients after resection of pancreatic adenocarcinoma.

BACKGROUND: The prognostic factors related to lymph node involvement [lymph node status, the number of positive lymph nodes, lymph node ratio (LNR)] and the number of nodes evaluated in patients with pancreatic adenocarcinoma after pancreatectomy are poorly defined. METHODS: A total of 167 patients who had undergone resection of pancreatic adenocarcinoma from February 2010 to August 2011 were included in this study. Histological examination was performed to evaluate the tumor differentiation and lymph node involvement. Univariate and multivariate analyses were made to determine the relationship between the variables related to nodal involvement and the number of nodes and survival. RESULTS: The median number of total nodes examined was 10 (range 0-44) for the entire cohort. The median number of total nodes examined in node-negative (pN0) patients was similar to that in node-positive (pN1) patients. Patients with pN1 diseases had significantly worse survival than those with pN0 ones (P=0.000). Patients with three or more positive nodes had a poorer prognosis compared with those with the negative nodes (P=0.000). The prognosis of the patients with negative nodes was similar to that of those with one to two positive nodes (P=0.114). The median survival of patients with an LNR ≥0.4 was shorter than that of patients with an LNR <0.4 in the pN1 cohort (P=0.014). No significance was found between the number of total nodes examined and the prognosis, regardless of the cutoff of 10 or 12 and in the entire cohort or the pN0 and pN1 groups. Based on the multivariate analysis of the entire cohort and the pN1 group, the nodal status, the number of positive nodes and the LNR were all associated with survival. CONCLUSIONS: In addition to the nodal status, the number of positive nodes and the LNR can serve as comprehensive factors for the evaluation of nodal involvement. This approach may be more effective for predicting the survival of patients with pancreatic adenocarcinoma after pancreatectomy.

Re-evaluation of ABO gene polymorphisms detected in a genome-wide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population.

Pancreatic cancer is a fatal malignancy with an increasing incidence in Shanghai, China. A genome-wide association study (GWAS) and other work have shown that ABO alleles are associated with pancreatic cancer risk. We conducted a population-based case-control study involving 256 patients with pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) and 548 healthy controls in Shanghai, China, to assess the relationships between GWAS-identified ABO alleles and risk of PDAC. Carriers of the C allele of rs505922 had an increased cancer risk [adjusted odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.02-1.98] compared to TT carriers. The T alleles of rs495828 and rs657152 were also significantly associated with an elevated cancer risk (adjusted OR = 1.58, 95% CI: 1.17-2.14; adjusted OR = 1.51, 95% CI: 1.09-2.10). The rs630014 variant was not associated with risk. We did not find any significant gene-environment interaction with cancer risk using a multifactor dimensionality reduction (MDR) method. Haplotype analysis also showed that the haplotype CTTC was associated with an increased risk of PDAC (adjusted OR = 1.46, 95% CI: 1.12-1.91) compared with haplotype TGGT. GWAS-identified ABO variants are thus also associated with risk of PDAC in the Chinese population.

Dietary energy density is positively associated with risk of pancreatic cancer in urban Shanghai Chinese.

Regular consumption of energy-dense foods predisposes to obesity and type 2 diabetes, both of which are suggested risk factors for pancreatic cancer. The aim of this study was to investigate whether energy density of foods is an independent risk factor for pancreatic cancer. In this population-based case-control study in urban Shanghai, 908 patients with pancreatic cancer and 1067 normal controls, aged 35-79 y, were recruited. The energy density for overall diet was calculated from food-frequency questionnaire data. Energy density (adjusted for age, sex, and total energy intake) was significantly higher in cases (6.08 ± 0.04 kJ/g) than in controls (5.91 ± 0.04 kJ/g) (P = 0.003). Energy density was positively associated with pancreatic cancer risk (OR: 1.16 per unit increase; 95% CI: 1.07, 1.27; P < 0.001). In adjusted analysis, the risk of pancreatic cancer was 72% greater (OR: 1.72; 95% CI: 1.25, 2.35; P = 0.001) in the highest quintile of energy density compared with the lowest quintile. In this case-control study, dietary energy density is positively associated with risk of pancreatic cancer. This association should be further investigated in prospective studies.

Characteristics of Notch2(+) pancreatic cancer stem-like cells and the relationship with centroacinar cells.

Notch2, a surface marker in cell lines, is used to isolate, identify and localise pancreatic cancer stem-like cells and is a target for therapy of these cells. Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines, and Notch2(+) cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic activated cell sorting (MACS). Expression of stem cell-related markers, OCT4, Nanog and PDX1, were measured by immunofluorescent (IF) staining. Expression of Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2(+) cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was used to treat Notch2(+) Bxpc-3 cells, and their vitalities were subsequently measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was observed in Notch2(+) cells. Notch2(+) cells at centroacinar cell (CAC) and terminal ductal locations expressed AQP1 and AQP5. They were strongly tumourigenic in mice, and CE inhibited proliferation of Notch2(+) Bxpc-3 cells to some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic cancer stem cells. Notch2(+) cells in human pancreatic cancer Bxpc-3 and Panc-1 cell lines had the properties of cancer stem cells. The results suggest that Notch2(+) pancreatic cancer stem-like cells had a close relationship with CAC.

Ligamentum teres hepatis patch enhances the healing of pancreatic fistula after distal pancreatectomy.

Pancreatic fistula is one of the most common complications after the distal pancreatectomy. Many methods have been tried to solve the problem, but no one is optimal, especially for the soft pancreatic stump cases. This study used ligamentum teres hepatis as a patch to cover the pancreatic stump. Between October 2010 and December 2012, seventy-seven patients who had undergone distal pancreatectomy with a soft pancreatic stump were divided into two groups: group A (n=39, patients received conventional ligated main pancreatic duct method) and group B (n=38, patients underwent a coverage procedure). Patients in group A had a longer recovery from postoperative pancreatic fistula than those in group B (16.4+/-3.5 vs 10.8+/-1.6 days, P<0.05). The coverage procedure with ligamentum teres hepatis is a safe, effective and convenient method for patients with a soft pancreas remnant during distal pancreatectomy.

Carbon nanotubes in cancer diagnosis and therapy.

During the past years, great progress has been made in the field of nanomaterials given their great potential in biomedical applications. Carbon nanotubes (CNTs), due to their unique physicochemical properties, have become a popular tool in cancer diagnosis and therapy. They are considered one of the most promising nanomaterials with the capability of both detecting the cancerous cells and delivering drugs or small therapeutic molecules to these cells. Over the last several years, CNTs have been explored in almost every single cancer treatment modality, including drug delivery, lymphatic targeted chemotherapy, thermal therapy, photodynamic therapy, and gene therapy. In this review, we will show how they have been introduced into the diagnosis and treatment of cancer. Novel SWNT-based tumor-targeted drug delivery systems (DDS) will be highlighted. Furthermore, the in vitro and in vivo toxicity of CNTs reported in recent years will be summarized.

Active surveillance in metastatic pancreatic neuroendocrine tumors: A 20-year single-institutional experience.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous and indolent; systemic therapy is not essential for every patient with metastatic PanNET. The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis, if the patient has stable disease. However, specific factors that influence surveillance were not mentioned. In addition, data regarding the period of active surveillance in patients with metastatic PanNET are lacking. AIM: To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs). METHODS: Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled. Time to disease progression (TTP) and time to initiation of systemic therapy were determined. RESULTS: Thirty-one (40.8%) patients had recurrent liver disease after R0 resection; 45 (59.2%) were diagnosed with liver metastasis. The median follow-up period was 42 mo and 90.7% patients were observed to have disease progression. The median TTP (mTTP) was 10 mo. Multivariate analysis showed that the largest axis of the liver metastasis > 5 mm (P = 0.04), non-resection of the primary tumor (P = 0.024), and T3-4 stage (P = 0.028) were associated with a shorter TTP. The mTTP in patients with no risk factors was 24 mo, which was significantly longer than that in patients with one (10 mo) or more (6 mo) risk factors (P < 0.001). A nomogram with three risk factors showed reasonable calibration, with a C-index of 0.603 (95% confidence interval: 0.47-0.74). CONCLUSION: Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors, and other patients progressed rapidly without treatment. Further studies with a larger sample size and a control group are needed.

Haemoglobin, albumin, lymphocyte and platelet predicts postoperative survival in pancreatic cancer.

BACKGROUND: Systemic inflammation and nutrition status play an important role in cancer metastasis. The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP), consisting of haemoglobin, albumin, lymphocytes, and platelets, is considered as a novel marker to reflect both systemic inflammation and nutrition status. However, no studies have investigated the relationship between HALP and survival of patients with pancreatic cancer following radical resection. AIM: To evaluate the prognostic value of preoperative HALP in pancreatic cancer patients. METHODS: The preoperative serum levels of hemoglobin, albumin, lymphocyte counts, and platelet counts were routinely detected in 582 pancreatic adenocarcinoma patients who underwent radical resection. The relationship between postoperative survival and the preoperative level of HALP was investigated. RESULTS: Low levels of HALP were significantly associated with lymph node metastasis (P = 0.002), poor tumor differentiation (P = 0.032), high TNM stage (P = 0.008), female patients (P = 0.005) and tumor location in the head of the pancreas (P < 0.001). Low levels of HALP were associated with early recurrence [7.3 mo vs 16.3 mo, P < 0.001 for recurrence-free survival (RFS)] and short survival [11.5 mo vs 23.6 mo, P < 0.001 for overall survival (OS)] in patients with resected pancreatic adenocarcinoma. A low level of HALP was an independent risk factor for early recurrence and short survival irrespective of sex and tumor location. CONCLUSION: Low levels of HALP may be a significant risk factor for RFS and OS in patients with resected pancreatic cancer.

Preparation of albumin nanospheres loaded with gemcitabine and their cytotoxicity against BXPC-3 cells in vitro.

AIM: To optimize formulation methods for loading gemcitabine (GEM), the main drug against pancreatic cancer, into albumin nanoparticles for extended blood circulation and improved efficacy. METHODS: GEM was loaded into two sizes of disolvation-crosslinked bovine serum albumin nanoparticles, with a mean diameter of 109.7 nm and 405.6 nm, respectively, by co-precipitation (the direct method) and follow-up adsorption (the indirect method). The antitumor activities of the two nanoparticulate formulations, were evaluated according to their anti-proliferative effects on the human pancreatic cell line BXPC-3, which were assessed using the MTT assay. RESULTS: The two nanoparticulate formulations, created by direct co-precipitation and indirect adsorption, possessed smooth surfaces and high drug loading efficiencies, 83% and 93% at 11% and 13% drug loading, respectively. The two formulations released GEM for 8 and 12 h, respectively, and significantly improved anti-BXPC-3 proliferation effects, as compared with the GEM solution and the drug-free albumin particles. CONCLUSION: Co-precipitating and adsorbing GEM into albumin particles resulted in sustained-release nanoparticulate formulations with improved antitumor cytotoxicity. The result suggests that this is a useful formulation strategy for improving the antitumor efficacy of GEM.

Neoadjuvant Therapy is Essential for Resectable Pancreatic Cancer.

BACKGROUND: Awareness of the benefits of neoadjuvant therapy is increasing, but its use as an initial therapeutic option for patients with resectable pancreatic cancer remains controversial, especially for those patients without high-risk prognostic features. Even for patients with high-risk features who are candidates to receive neoadjuvant therapy, no standard regimen exists. METHODS: In this review, we examined available data on the neoadjuvant therapy in patients with resectable pancreatic cancer, including prospective studies, retrospective studies, and ongoing clinical trials, by searching PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Cochrane Library. The characteristics and results of screened studies were described. RESULTS: Retrospective and prospective studies with reported results and ongoing randomized studies were included. For patients with resectable pancreatic cancer, neoadjuvant therapy provides benefits such as increased survival, decreased risk of comorbidities and mortality, and improved cost-effectiveness due to an increased completion rate of multimodal treatment. Highly active regimens such as FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel are considered acceptable therapeutic regimens. Additionally, platinum-containing regimens other than FOLFIRINOX are acceptable for selected patients. Other therapies, such as chemoradiation treatment, immuno-oncology agents, and targeted therapies are being explored and the results are highly anticipated. CONCLUSION: This review highlights the benefits of neoadjuvant therapy for resectable pancreatic cancer. Some regimens are currently acceptable, but need more evidence from well-designed clinical trials or should be used after being carefully examined by a multidisciplinary team.

SRPX2 and RAB31 are effective prognostic biomarkers in pancreatic cancer.

Introduction: SRPX2 and RAB31 play important roles in tumorigenesis and metastasis; however, their prognostic value in pancreatic cancer remains unclear. This study aimed to investigate the potential interactions and effects of SRPX2 and RAB31 on the diagnosis and prognosis of pancreatic cancer. Methods: The expression of SRPX2 and RAB31 in pancreatic tumor tissues and cells was evaluated through database mining of the Oncomine, Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and validated the results through immunohistochemistry (IHC) and Western blot in our clinical database. Protein-protein interactions were explored by immunofluorescence and Co-immunoprecipitation (Co-IP). Two hundred tissue microarray specimens from patients (79 training and 121 validation), who underwent curative pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) were used. Additionally, the association between the SRPX2 and RAB31 and prognosis of PDAC patients after surgery was analyzed. Results: The expression of SRPX2 and RAB31 was highly increased in pancreatic cancer, and there was a significant positive correlation between these two proteins. Co-IP showed the direct interaction between SRPX2 and RAB31. Kaplan-Meier analysis showed that positive expression of SRPX2 and RAB31 was associated with reduced disease-free survival (DFS) and overall survival (OS) of PDAC patients in the training set and the validation sets. Furthermore, multivariate analysis indicated that the 8th edition TNM stage and combination of SRPX2 and RAB31 were independent prognostic factors that associated with OS and DFS in the training, and the validation sets, respectively. Conclusions: The combination of SRPX2 and RAB31 can be important markers for the prognosis of pancreatic cancer.