Lie Yao

The microRNA-218 and ROBO-1 signaling axis correlates with the lymphatic metastasis 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.

Gemcitabine-loaded albumin nanospheres (GEM-ANPs) inhibit PANC-1 cells in vitro and in vivo

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.

MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1

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.

Adult primary retroperitoneal cavernous hemangioma: a case report

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.

Is routine drainage necessary after pancreaticoduodenectomy

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.

Accuracy of routine multidetector computed tomography to identify arterial variants in patients scheduled for pancreaticoduodenectomy

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.

Novel and supplementary management of pancreatic fluid collections: Endoscopic ultrasound-guided drainage

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.

Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA (lncRNA) in Human Pancreatic Ductal Adenocarcinoma:

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 <0.05). These differentially expressed long noncoding RNAs were not evenly distributed among chromosomes in human genome. Hierarchical clustering of these differentially expressed long noncoding RNAs revealed large variabilities in long noncoding RNA expression among individual patient, indicating that certain long noncoding RNAs could play a unique role or be used as a biomarker for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-γ-mediated signaling pathway, mitotic cell cycle and proliferation, extracellular matrix receptor interaction, focal adhesion, and regulation of actin cytoskeleton. The co-expression network analysis detected 393 potential interactions between 80 differentially expressed long noncoding RNAs and 105 messenger RNAs. We experimentally verified 7 most markedly dysregulated long noncoding RNAs from the network. Conclusion: Our study provided a genome-wide survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA co-regulation networks in pancreatic ductal adenocarcinoma tissue. These dysregulated long noncoding RNA/messenger RNA networks could be used as biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its subtype, predict prognosis, and evaluate treatment efficacy.

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

BackgroundPlatelets 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.MethodsA 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).ResultsTIPs, 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).ConclusionTIPs 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.

Radical resection and enucleation in Chinese adolescents with pancreatic tumors: A 15-year case series

Abstract 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.