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Surgeries achieving maximal tumor resection remain the major effective treatment of pancreatic cancer. Rapid and precise intraoperative diagnosis of pancreatic tissues is critical for optimum surgical outcomes but is challenging for the current staining-based histological methods. We demonstrated that label-free coherent nonlinear optical microscopy with combined stimulated Raman scattering (SRS) and second harmonic generation (SHG) could reveal key diagnostic features of both normal and cancerous human pancreatic tissues. Adjacent pairs of tissue sections from resection margins of 37 patients were imaged by SRS and hematoxylin and eosin staining for direct comparison, demonstrating high diagnostic concordance (Cohen's kappa, κ > 0.97) between them. Fresh unprocessed tissues showed well-preserved histoarchitectures including pancreatic ducts, islets, acini, and nerves. Moreover, the area ratios of collagen fibers were analyzed and found to correlate with the drainage pancreatic amylase level (odds ratio = 28.0, p = 0.0017). Our results indicated that SRS/SHG histology provides potential for rapid intraoperative diagnosis of pancreatic cancer as well as a predictive value of postoperative pancreatic fistula.

BACKGROUND Total pancreatectomy (TP) is usually considered a therapeutic option for pancreatic cancer in which Whipple surgery and distal pancreatectomy are undesirable, but brittle diabetes and poor quality of life (QoL) remain major concerns. A subset of patients who underwent TP even died due to severe hypoglycemia. For pancreatic cancer involving the pancreatic head and proximal body but without invasion to the pancreatic tail, we performed partial pancreatic tail preserving subtotal pancreatectomy (PPTP-SP) in selected patients, in order to improve postoperative glycemic control and QoL without compromising oncological outcomes. AIM To evaluate the efficacy of PPTP-SP for patients with pancreatic cancer. METHODS We retrospectively reviewed 56 patients with pancreatic ductal adenocarcinoma who underwent PPTP-SP (n = 18) or TP (n = 38) at our institution from May 2014 to January 2019. Clinical outcomes were compared between the two groups, with an emphasis on oncological outcomes, postoperative glycemic control, and QoL. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and EORTC PAN26). All patients were followed until May 2019 or until death. RESULTS A total of 56 consecutive patients were enrolled in this study. Perioperative outcomes, recurrence-free survival, and overall survival were comparable between the two groups. No patients in the PPTP-SP group developed cancer recurrence in the pancreatic tail stump or splenic hilum, or a clinical pancreatic fistula. Patients who underwent PPTP-SP had significantly better glycemic control, based on their higher rate of insulin-independence (P = 0.014), lower hemoglobin A1c (HbA1c) level (P = 0.046), lower daily insulin dosage (P < 0.001), and less frequent hypoglycemic episodes (P < 0.001). Global health was similar in the two groups, but patients who underwent PPTP-SP had better functional status (P = 0.036), milder symptoms (P = 0.013), less severe diet restriction (P = 0.011), and higher confidence regarding future life (P = 0.035). CONCLUSION For pancreatic cancer involving the pancreatic head and proximal body, PPTP-SP achieves perioperative and oncological outcomes comparable to TP in selected patients while significantly improving long-term glycemic control and QoL.

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

BACKGROUND: Perioperative glycemic status after pancreatic surgery has never been described. However, it’s essential for optimal perioperative glucose management and understanding the pathogenesis of new-onset diabetes mellitus (NODM) after pancreatectomy. Continuous glucose monitoring (CGM) system provides us a helpful tool for closely monitoring and studying perioperative glucose change. This study tried to describe and compare perioperative glucose level and glycemic variability between different types of pancreatic surgeries via CGM device. METHODS: This study was designed as a prospective observational study. Eighteen patients were enrolled and were grouped by different types of surgery received: control group (CTRL), pancreaticoduodenectomy (PD), distal pancreatectomy (DP), and total pancreatectomy (TP). CGM devices were implanted and initiated right after the surgery. Mean glucose value (MGV), coefficient of variation (CV), mean of daily difference (MODD), continuous overall net glycemic action (CONGA), and time above range (TAR)/time below range (TBR) was compared between groups to assess glucose level and glycemic variability. RESULTS: TP showed the highest MGV and CV among all groups (P

Functionalized multi‐walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP‐1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP‐1–conjugated functionalized multi‐walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP‐1–conjugated functionalized multi‐walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi‐walled carbon nanotubes, cellular uptake of LyP‐1–functionalized multi‐walled carbon nanotubes was shown to be increased. Compound of LyP‐1–functionalized multi‐walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP‐1‐fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP‐1–functionalized multi‐walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP‐1–functionalized multi‐walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.

Background: : Postoperative pancreatic fistula (POPF) is one of the most common complications and the leading cause of morbidity and mortality after pancreatic operation with pancreatojejunostomy (PJ). Many strategies have been used to prevent the incidence of POPF, among which drainage of pancreatic juice is effective. There are two types of drainage methods used in clinical practice; however, the method with a superior effect remains unknown. This study compared the effect of external and internal drainage without stent (in other words, no drainage, only PJ by duct-to-mucosa) on the incidence of clinically relevant POPF (CR-POPF) to provide evidence to select a better drainage scheme in clinical practice. Methods: Overall, 520 patients undergoing pancreatic operation, including PJ were included in this single-centre study and were divided into two groups according to drainage methods. We compared the incidence of CR-POPF between the two groups and performed stratified analysis according to the Fistula Risk Score (FRS) and pancreatic gland texture. Factors such as gender, age, Body Mass Index (BMI), operative procedure, and drainage methods were included in univariable and multivariable analyses. Results: The incidence rate of CR-POPF between two groups was significantly different (23.3% vs 13.6%, P

Hyaluronan-binding protein 1 (HABP1) overexpression has been confirmed in different malignancies and found to be strongly associated with tumor development and progression. The aim of the present study was to explore the impact of HABP1 in pancreatic ductal adenocarcinoma (PDAC) patients.HABP1 expression was evaluated in 89 PDAC specimens.The expression of HABP1 was significantly higher in tumor tissues than that in adjacent normal tissues. High nucleus HABP1 expression and high cytoplasm HABP1 expression were both detected in PDAC tissues. Overall survival analysis by optical density showed that the mean survival was similar between patients with low and high optical density values of HABP1 expression (P = 0.312). The similar result was also found between patients with low-moderate or high nucleus HABP1 expression (P = 0.275). However, the mean survival was significantly poorer in patients with cytoplasm HABP1 overexpression (P 0.001). High cytoplasm HABP1 expression was strongly correlated with late tumor stages, arterial involvement, lymph node metastasis and carbohydrate antigen 19-9 levels.High cytoplasm HABP1 expression may prove to be a predictor of poor survival and late tumor stage in PDAC patients. HABP1 could serve as a promising biomarker to identify subsets of PDAC patients with high malignant clinical behavior.

Maximal resection of tumor while preserving the adjacent healthy tissue is particularly important for larynx surgery, hence precise and rapid intraoperative histology of laryngeal tissue is crucial for providing optimal surgical outcomes. We hypothesized that deep-learning based stimulated Raman scattering (SRS) microscopy could provide automated and accurate diagnosis of laryngeal squamous cell carcinoma on fresh, unprocessed surgical specimens without fixation, sectioning or staining. Methods: We first compared 80 pairs of adjacent frozen sections imaged with SRS and standard hematoxylin and eosin histology to evaluate their concordance. We then applied SRS imaging on fresh surgical tissues from 45 patients to reveal key diagnostic features, based on which we have constructed a deep learning based model to generate automated histologic results. 18,750 SRS fields of views were used to train and cross-validate our 34-layered residual convolutional neural network, which was used to classify 33 untrained fresh larynx surgical samples into normal and neoplasia. Furthermore, we simulated intraoperative evaluation of resection margins on totally removed larynxes. Results: We demonstrated near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) between SRS and standard histology as evaluated by three pathologists. And deep-learning based SRS correctly classified 33 independent surgical specimens with 100% accuracy. We also demonstrated that our method could identify tissue neoplasia at the simulated resection margins that appear grossly normal with naked eyes. Conclusion: Our results indicated that SRS histology integrated with deep learning algorithm provides potential for delivering rapid intraoperative diagnosis that could aid the surgical management of laryngeal cancer.

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.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).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).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.

Zhongyi Guo,1 Feng Wang,2 Yang Di,1 Lie Yao,1 Xinzhe Yu,1 Deliang Fu,3 Ji Li,3 Chen Jin1 1Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China; 2School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, China; 3Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, China Purpose: Gemcitabine is currently the standard first-line chemotherapeutic drug for treating pancreatic cancer. However, many factors can contribute to gemcitabine resistance. One of the most important reasons is the low hENT1 expression. In this study, we tested the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression. Materials and methods: S-(4-nitrobenzyl)-6-thioinosine was utilized to inhibit the activity of hENT1 and simulate low hENT1 expression. Growth inhibition assays and cell cycle and apoptosis analyses were performed on human pancreatic cancer cell lines such as BxPC-3 and SW1990. The in vivo antitumor effect was studied by using patient-derived xenograft (PDX) models. The in vivo toxicity assessment was performed on healthy Kunming mice. Results: In in vitro studies, GEM-HSA-NP showed its ability to inhibit cell proliferation, arrest cell cycle and induce apoptosis when tumor cells were resistant to gemcitabine. In in vivo studies, GEM-HSA-NP was more effective than gemcitabine on inhibiting tumor growth whether the expression levels of hENT1 were high or low in PDX models. The in vivo toxicity assessment showed that the biotoxicity of GEM-HSA-NP did not increase compared with gemcitabine. Conclusion: GEM-HSA-NP can overcome gemcitabine resistance induced by low hENT1 expression, which suggests its potential role for the clinical application. Keywords: pancreatic cancer, gemcitabine resistance, albumin nanoparticles, low hENT1 expression, PDX model

Evidence shows that portal vein resection (PVR) increase the resectability but does little benefit to overall survival in all pancreatic ductal adenocarcinoma (PDAC) patients. But for patients with portal vein involvement, PVR is the only radical choice. But whether the PDAC patients with portal vein involvement would benefit from radical pancreaticoduodenectomy with PVR or not is controversial. All 204 PDAC patients with portal vein involvement were enrolled in this study [PVR group, n=106; surgical bypass (SB) group, n=52; chemotherapy group, n=46]. Overall survival and prognostic factors were analyzed among three groups. Moreover, a literature review of 13 studies were also conducted. Among 3 groups, patients in PVR group achieved a significant longer survival (median survival: PVR group, 22.83 months; SB group, 7.26 months; chemotherapy group, 10.64 months). Therapy choice [hazard ratio (HR) =1.593, 95% confidence interval (CI) 1.323 to 1.918, P

AIM To compare efficacy and safety of endoscopic ultrasound (EUS)-guided and surgical drainage in pancreatic fluid collection management. METHODS Data were obtained retrospectively from January 2012 to December 2016. Patients with pancreatic fluid collection were performed EUS-guided or surgical procedure. Main outcome measures including clinical efficiency, complication, duration of procedures, hospital stay and cost were analyzed. RESULTS Thirty-six patients were enrolled into the study, including 14 in endoscopic group while 22 in the surgical group. Twelve (86%) patients were treated successfully by endoscopic approach while 21 (95%) patients benefited through surgical procedure. Endoscopic treatment had higher recurrence and complication rates than surgery, resulting in more re-interventions. Meanwhile, duration of procedure, hospital stay and cost were significantly lower in endoscopic group. CONCLUSION Both approaches were effective and safe. EUS-guided approach should be the first-line treatment in mild and simple cases, while surgical approach should be considered as priority in severe and complex cases.

Background The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. Methods Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation. Results A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin. Conclusion Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.

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. 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). NETs were associated with OS (both, P

For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P

The main focus of the present study was to evaluate whether ABC transporter family promoter methylation predicted multidrug resistance in gemcitabine-resistant cancer cell lines (BxPC-3/Gem and PANC-1/Gem). Using low concentrations of gemcitabine, the cell lines acquired drug resistance with different initial gemcitabine concentrations. A novel technology, methylation-sensitive high-resolution melting, was used to monitor the dynamic changes of ABC transporter family promoter methylation, including ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C (ABCC) and ATP binding cassette subfamily G member 2 (ABCG2) mRNA expression. It was revealed that, with elevation of initial gemcitabine concentration, expression of ABCB1, ABCC and ABCG2 mRNA and corresponding downstream proteins was increased while promoter methylation was decreased. These discoveries indicate that promoter methylation of ABCB1, ABCC and ABCG2 may be a valuable indicator of drug-resistance characteristics in BxPC-3/Gem and PANC-1/Gem cells via quantitative and simultaneous detection. These results also implied that MDR in pancreatic cancer not only arises from gene mutation, but also originates from promoter methylation.

Background: Long noncoding RNAs have been shown to play crucial roles in cancer biology, while the long noncoding RNA landscapes of pancreatic ductal adenocarcinoma have not been completely characterized. We aimed to determine whether long noncoding RNA could serve as early diagnostic biomarkers for pancreatic ductal adenocarcinoma. Method: We conducted a genome-wide microarray analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous tissues from 8 Chinese patients. Results: A total of 3352 significantly differentially expressed long noncoding RNAs were detected. Of total, 1249 long noncoding RNAs were upregulated and 2103 were downregulated (fold change ≥2, P < 0.05, FDR

Introduction Afferent loop syndrome (ALS) is a rare and dreaded complication after pancreaticoduodenectomy (PD). Malignant ALS after PD is usually difficult to manage due to patients’ poor condition. Effective and safe therapeutic strategies for these patients are reported scarcely at present. Aim To analyze and evaluate the clinical characteristics and treatment of these patients. Material and methods We analyzed 3 patients with malignant ALS after PD. They were treated by endoscopic enteral metal stent placement in our hospital. Meanwhile we retrospectively reviewed 49 cases with ALS after PD through available English literature. All these patients’ clinical features, laboratory study, treatment and outcome were evaluated. Results A total of 52 cases were analyzed in the study. The most common presenting symptoms of ALS after PD were jaundice (56.5%), upper abdominal pain (45.7%), fever (26.1%), and vomiting (23.9%). Sixty percent of ALS cases were caused by tumor recurrence. The mean time from prior surgery to diagnosis of ALS was 13.3 months. The rates of treatment with the endoscopic approach, percutaneous stenting or drainage, surgery, and the conservative method were 40.4%, 32.7%, 11.5%, and 15.4%, respectively. Endoscopic enteral metal stent placement proved more effective and less invasive in the treatment of malignant ALS after PD. Conclusions Cholangitis and cholangiectasis are the major manifestations of malignant ALS after PD. Invasive interventions are enjoying more and more acceptance for treatment. Endoscopic enteral metal stent placement appears to be a promising technique with effective palliation in these patients.

miRNA-218 is a highlighted tumor suppressor and its underlying role in tumor progression is still unknown. Here, we restored the expression of miRNA-218 in pancreatic cancer to clarify the function and potent downstream pathway of miRNA-218. The expressions of both miRNA-218 and its potent target gene ROBO1 were revealed by RT-PCR and western blotting analysis. Transfection of miRNA-218 precursor mimics and luciferase assay were performed to elucidate the regulation mechanism between miRNA-218 and ROBO1. Cells, stably expressing miRNA-218 followed by forced expression of mutant ROBO1, were established through co-transfections of both lentivirus vector and plasmid vector. The cell migration and invasion abilities were evaluated by migration assay and invasion assay respectively. An increased expression of ROBO1 was revealed in cell BxPC-3-LN compared with cell BxPC-3. Elevated expression of miRNA-218 would suppress the expression of ROBO1 via complementary binding to a specific region within 3'UTR of ROBO1 mRNA (sites 971-978) in pancreatic cancer cells. Stably restoring the expression of miRNA-218 in pancreatic cancer significantly downregulated the expression of ROBO1 and effectively inhibited cell migration and invasion. Forced expression of mutant ROBO1 could reverse the repression effects of miRNA-218 on cell migration and invasion. Consequently, miRNA-218 acted as a tumor suppressor in pancreatic cancer by inhibiting cell invasion and migration. ROBO1 was a functional target of miRNA-218's downstream pathway involving in cell invasion and migration of pancreatic cancer.

Pancreatic cancer is known for its poor prognosis and early lymphatic metastasis is a notable characteristic. microRNAs (miRNAs) have been shown to be involved in the initiation and progression of pancreatic cancer. We, therefore, established a screening strategy to find miRNAs related to the lymphatic metastasis of pancreatic cancer and explored the target genes of miRNAs. miRNA array profiles were analyzed in tissue samples [pancreatic ductal adenocarcinoma (PDAC) and matched adjacent benign tissues (MAT)] and cell lines (BxPC-3-LN and BxPC-3). Combined analysis of profiling data from tissue samples and cell lines was used to identify miRNAs related to the lymphatic metastasis of pancreatic cancer. The expression levels of miRNAs were confirmed by real‑time reverse transcription PCR (RT-PCR) in tissue samples and cell lines. The correlation between miRNAs and clinicopathological characteristics was investigated. The expression features of miRNAs in pancreatic cancer, precursor lesions and metastatic lymph nodes were characterized by in situ hybridization (ISH). Predicted target genes of miRNAs were validated by RT-PCR and the protein levels of target genes were revealed by western blotting. Seventy and 63 miRNAs were differentially expressed in pancreatic cancer and BxPC-3-LN, compared to MAT and BxPC-3, respectively. Combined microarray analysis found 4 co-differentially expressed miRNAs (miRNA-663, miRNA-145, miRNA-218 and let-7) related to the lymphatic metastasis of pancreatic cancer. miRNA-218 was significantly downregulated in BxPC-3-LN (fold-change>10) and the expression levels of miRNA-218 were confirmed by RT-PCR. The group with lymph node metastasis and the elder group (age>64) showed lower expression of miRNA-218 (P=0.003 and 0.002), compared to patients without lymph nodes metastasis and patients in the younger group (age≤64), respectively. The expression of miRNA‑218 showed a decreasing trend from normal acinar/ductal epithelium, intraductal papillary mucinous neoplasm (IPMN), pancreatic cancer to metastatic lymph nodes by ISH. Among 8 predicted target genes of miRNA-218, rodent bone (ROBO-1) was confirmed to be upregulated in both mRNA and protein levels in pancreatic cancer. In conclusion, we established a screening strategy based on microarray results and found miRNA-218 to be a notable gene related to lymphatic metastasis of pancreatic cancer. Downregulation of miRNA-218 and upregulation of ROBO-1 were first demonstrated in pancreatic cancer. The miRNA-218 and ROBO-1 signaling axis may contribute to the lymphatic metastasis of pancreatic cancer.

Detection of circulating tumor cells (CTCs) has become widely used as a liquid biopsy for many patients. In pancreatic cancer patients, there have been a number of published reports on the efficacy of CTCs in the diagnosis and prognosis of pancreatic cancer, and in the evaluation of response to treatment. We systematically reviewed the diagnosis efficiency and prognostic value of CTCs reported in the literature. We found that the frequency of CTCs is rare, limited to a certain degree by the current enrichment and detection methodologies. The sensitivity of CTCs for diagnosis is variable likely due to the different stages of the disease at the time of diagnosis (varied from 25.0% to 100.0%) but specificity remained relatively high (varied from 99.7% to 100.0%). However, pooled results from meta-analyses (patients with CTC positivity had worse overall survival than patients with CTC negativity) demonstrated that CTCs could be used as an effective tool in the prognosis prediction in pancreatic cancer patients.

With the development of imaging technology and surgical techniques, pancreatic resections to treat pancreatic tumors, ampulla tumors, and other pancreatic diseases have increased. Pancreaticoduodenectomy, one type of pancreatic resection, is a complex surgery with the loss of pancreatic integrity and various anastomoses. Complications after pancreaticoduodenectomy such as pancreatic fistulas and anastomosis leakage are common and significantly associated with patient outcomes. Pancreatic fistula is one of the most important postoperative complications; this condition can cause intraperitoneal hemorrhage, septic shock, or even death. An effective way has not yet been found to avoid the occurrence of pancreatic fistula. In most medical centers, the frequency of pancreatic fistula has remained between 9% and 13%. The early detection and routine drainage of anastomotic fistulas, pancreatic fistulas, bleeding, or other intra-abdominal fluid collections after pancreatic resections are considered as important and effective ways to reduce postoperative complications and the mortality rate. However, many recent studies have argued that routine drainage after abdominal operations, including pancreaticoduodenectomies, does not affect the incidence of postoperative complications. Although inserting drains after pancreatic resections continues to be a routine procedure, its necessity remains controversial. This article reviews studies of the advantages and disadvantages of routine drainage after pancreaticoduodenectomy and discusses the necessity of this procedure.

With the development of nanotechnology, special attention has been given to the nanomaterial application in tumor treatment. Here, a modified desolvation-cross-linking method was successfully applied to fabricate gemcitabine-loaded albumin nanospheres (GEM-ANPs), with 110 and 406 nm of mean diameter, respectively. The aim of this study was to assess the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. Intravenous injection of 406-nm GEM-ANPs exhibited a significant increase of gemcitabine in the pancreas, liver, and spleen of Sprague–Dawley rats (p < 0.05). Moreover, no signs of toxic side effects analyzed by blood parameter changes were observed after 3 weeks of administration although a high dose (200 mg/kg) of GEM-ANPs were used. Additionally, in PANC-1-induced tumor mice, intravenous injection of 406-nm GEM-ANPs also could effectively reduce the tumor volume by comparison with free gemcitabine. With these findings, albumin nanosphere-loading approach might be efficacious to improve the antitumor activity of gemcitabine, and the efficacy is associated with the size of GEM-ANPs.

Pancreatic tumors rarely occur in adolescents, and the appropriateness of radical resection for these patients remains controversial. Medical records were retrospectively reviewed for patients younger than 19 years who underwent radical resection or limited resection (enucleation) between 2000 and 2015. Patient demographics, clinical characteristics, operative details, growth, and survival were analyzed. During the study period, 11 adolescents (mean age, 16.18 years; standard deviation, 1.99; interquartile range, 15.0–18.0) underwent radical resection (n = 7) or enucleation (n = 4) to treat solid pseudopapillary tumors (n = 5), pancreatic neuroendocrine tumors (n = 5), or pancreatic ductal adenocarcinoma (n = 1). None of the 7 patients who underwent radical resection experienced recurrence or serious complications, while 3 of 4 patients who underwent enucleation experienced recurrence (P = 0.02). Recurrence-free survival was slightly longer in patients who underwent radical resection, and this procedure did not appear to affect adolescent growth and development. Radical resection might be safe and effective for adolescents with pancreatic tumors.

Primary retroperitoneal cavernous hemangioma (PRCH) in an adult is extremely rare. We report on the diagnosis and treatment of a patient with PRCH with subtle clinical features and atypical findings on imaging scans. A 38-year-old man was admitted to hospital with a 5-day history of epigastralgia after alcohol drinking. Using various imaging methods, we found a giant cyst-like retroperitoneal mass compressing the surrounding organs. Surgical resection of the tumor was performed, and the mass was found to be a cavernous hemangioma measuring 90 × 80 × 60 mm, with a thick fibrotic wall and extensive intracystic hemorrhage. Physicians should be aware that PRCH may mimic a cystic neoplasm, and that a large tumor size probably indicates intracystic hemorrhage. Surgical resection is a curative approach for PRCH.

The aim of this study is to summarize the experience of preoperative diagnosis for nonfunctioning pancreatic neuroendocrine tumors (NFPNETs). The medical records of patients with NFPNETs were identified from 2001 to 2009 in a single center. They were all reviewed and analyzed for their demographics, clinical presentation, preoperative laboratory evaluation and radiographic characterization. Twenty-six patients (11 men and 15 women) in the past 8 years were diagnosed with NFPNETs. Almost all patients had the normal level of exocrine tumor markers. Although it was not difficult to find tumors by traditional imaging modalities including CT and MRI, the misdiagnosis rate was as high as 81.2%. Perfusion CT was helpful to predict the biological behavior of tumors and even identified NFPNETs as benign or malignant. The preoperative diagnosis for NFPNETs can be confirmed by one or the combination of CgA, perfusion CT, FNA-EUS, PET and octreoscans. NFPNETs should be aroused suspicion of normal exocrine tumor markers and relative specific imaging appearance, which can be proved by one or the combination of CgA, perfusion CT, FNA-EUS, PET and octreoscans.

Regional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.Patients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.The pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups.Multiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.

e15231 Background: Previous researches in pancreatic cancer demonstrated a negative correlation between SPARC expression in the primary tumor and survival benefit, but not for lymph node SPARC expr...

e15266 Background: The preoperative identification of pancreatic cystic neoplasms (PCNs) is crucial to the surgical decision-making. Besides pursuing better imaging and laboratory techniques, this ...

AIM: To assess the efficacy of cross-sectional multidetector computed tomography (MDCT) imaging without arterial reconstruction to identify aberrant right hepatic artery (RHA) and celiac artery stenosis (CAS) in patients scheduled for pancreaticoduodenectomy. METHODS: Patients with peri-ampullary and pancreatic head tumors who underwent routine preoperative MDCT and subsequent computed tomography (CT) angiography (CTA), conventional angiography or pancreaticoduodenectomy between September 2007 and August 2013 were identified. Retrospective analysis of imaging data was undertaken using CTA, conventional angiographic and surgical findings as the reference standards. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MDCT in evaluation of aberrant RHA and CAS were calculated. RESULTS: A group of 458 patients met the inclusion criteria of this study to detect aberrant RHA, and 181 cases were included to identify CAS. Fifty-four (11.8%) patients were confirmed to have aberrant RHA, while 12 (6.6%) patients with CAS were demonstrated. MDCT yielded an accuracy of 98.5%, sensitivity of 96.3% and specificity of 98.8% in the detection of aberrant RHA. The sensitivity, specificity, PPV and NPV of MDCT for detecting CAS were 58.3%, 98.2%, 70% and 97.1%, respectively. CONCLUSION: Routine MDCT is recommended such that surgeons and radiologists be alerted to the importance of arterial variants on preoperative CT scans in patients scheduled for pancreaticoduodenectomy.

e14651 Background: Early lymph node metastasis is one of the most important characteristic features of pancreatic ductal adenocarcinoma (PDAC) with a dismal prognosis. MicroRNAs (miRNAs) have been shown to have a role in oncogenesis, invasion, and metastasis via epigenetic posttranscriptional gene regulation. However lymphatic metastasis related miRNAs of pancreatic cancer (PC) has not been well documented. Methods: Through microarray analysis aberrantly expressing miRNAs potentially regulating lymphatic metastasis in PC were gained from PDAC tissue specimens and cell lines. Candidate miRNAs were confirmed in total 40 resected PDAC cases and cell lines by quantitative reverse transcription-PCR (qRT-PCR). In situ hybridization was performed to elucidate the expression features of miRNA-218 in PDAC, precursor lesions, metastatic lymph nodes and cell lines. Results: MiRNA-218 and other five miRNAs were found aberrantly expressing both in PDAC and BxPC-3-LN5 (cell line with high-metastasis characteristics) by microarray analysis. Down-regulated expression of miRNA-218 was validated in PDAC tissue samples (4 fold decrease) compared to adjacent benign tissue (p=0.006) and cell line BxPC-3-LN5 (3 fold decrease) compared to BxPC-3 (p=0.01). Clinicopathological data demonstrated inverse correlation of miRNA-218 expression with lymph node metastasis (p=0.045). Expression of miRNA-218 was down-regulated in IPMN and even decreased in PDAC in a grade-dependent manner. Almost negative expression of miRNA-218 was revealed in metastatic lymph nodes. Conclusions: Down-regulated expression of miRNA-218 in PDAC and its expression features in precursor lesions suggests a tumor suppressor action of miRNA-218 in PDAC. Decreased expression of miRNA-218 may be associated with lymphatic metastasis of PDAC and interpret the high-metastasis ability of BxPC-3-LN5 cell line.