An-Ping Su

MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the epithelial-mesenchymal transition in pancreatic cancer cells.

The platelet-derived growth factor (PDGF) signaling pathway has been found to play important roles in the development and progression of human cancers by regulating the processes of cell proliferation, apoptosis, migration, invasion, metastasis, and the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Moreover, PDGF signaling has also been found to alter the expression profile of miRNAs, leading to the reversal of EMT phenotype. Although the role of miRNAs in cancer has been documented, there are very few studies documenting the cellular consequences of targeted re-expression of specific miRNAs. Therefore, we investigated whether the treatment of human pancreatic cancer cells with PDGF could alter the expression profile of miRNAs, and we also assessed the cellular consequences. Our study demonstrates that miR-221 is essential for the PDGF-mediated EMT phenotype, migration, and growth of pancreatic cancer cells. Down-regulation of TRPS1 by miR-221 is critical for PDGF-mediated acquisition of the EMT phenotype. Additionally, the PDGF-dependent increase in cell proliferation appears to be mediated by inhibition of a specific target of miR-221 and down-regulation of p27Kip1.

Evaluation of the World Health Organization 2010 Grading System in Surgical Outcome and Prognosis of Pancreatic Neuroendocrine Tumors

Objective The objective of this study was to evaluate the clinical consistency of the new World Health Organization 2010 grading and the European Neuroendocrine Tumor Society 2006 TNM staging systems on the surgical outcome for patients with pancreatic neuroendocrine tumors (p-NETs). Moreover, we will discuss their prognostic value. Methods The medical records of 110 consecutive patients with p-NETs who were surgically treated in our center from January 2002 to December 2012 were reviewed. Results Sixty-five patients were diagnosed as having neuroendocrine tumor G1, 27 patients had neuroendocrine tumor G2, 14 patients had neuroendocrine carcinoma G3, and 4 patients had mixed adenoneuro endocrine carcinoma; the survival rates at 5 years were 82.6%, 52.7%, 25.7%, and 0%, respectively (P < 0.001). The TNM stage was I in 48 patients, II in 39 patients, III in 11 patients, and IV in 12 patients; the 5-year survival rates were 83.1%, 72.1%, 0%, and 0%, respectively (P < 0.001). The patients who underwent R0 resection gained a statistically longer survival time than those who did not (P < 0.001). Conclusions Both classifications accurately reflect the clinical outcome of p-NETs. Surgical margin, the World Health Organization 2010 grading, and the TNM staging systems may all be meaningful prognostic factors impacting the long-term survival of patients with p-NETs.

Does antecolic reconstruction for duodenojejunostomy improve delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy? A systematic review and meta- analysis

AIM To evaluate whether antecolic reconstruction for duodenojejunostomy (DJ) can decrease delayed gastric emptying (DGE) rate after pylorus-preserving pancreaticoduodenectomy (PPPD) through literature review and meta-analysis. METHODS Articles published between January 1991 and April 2012 comparing antecolic and retrocolic reconstruction for DJ after PPPD were retrieved from the databases of MEDLINE (PubMed), EMBASE, OVID and Cochrane Library Central. The primary outcome of interest was DGE. Either fixed effects model or random effects model was used to assess the pooled effect based on the heterogeneity. RESULTS Five articles were identified for inclusion: two randomized controlled trials and three non-randomized controlled trials. The meta-analysis revealed that antecolic reconstruction for DJ after PPPD was associated with a statistically significant decrease in the incidence of DGE [odds ratio (OR), 0.06; 95% CI, 0.02-0.17; P < 0.00001] and intra-operative blood loss [mean difference (MD), -317.68; 95% CI, -416.67 to -218.70; P < 0.00 001]. There was no significant difference between the groups of antecolic and retrocolic reconstruction in operative time (MD, 25.23; 95% CI, -14.37 to 64.83; P = 0.21), postoperative mortality, overall morbidity (OR, 0.54; 95% CI, 0.20-1.46; P = 0.22) and length of postoperative hospital stay (MD, -9.08; 95% CI, -21.28 to 3.11; P = 0.14). CONCLUSION Antecolic reconstruction for DJ can decrease the DGE rate after PPPD.

Is laparoscopic approach for pancreatic insulinomas safe? Results of a systematic review and meta-analysis.

BACKGROUND No consensus exists as to whether laparoscopic treatment for pancreatic insulinomas (PIs) is safe and feasible. The aim of this meta-analysis was to assess the feasibility, safety, and potential benefits of laparoscopic approach (LA) for PIs. The abovementioned approach is also compared with open surgery. METHODS A systematic literature search (MEDLINE, EMBASE, Cochrane Library, Science Citation Index, and Ovid journals) was performed to identify relevant articles. Articles that compare the use of LA and open approach to treat PI published on or before April 30, 2013, were included in the meta-analysis. The evaluated end points were operative outcomes, postoperative recovery, and postoperative complications. RESULTS Seven observational clinical studies that recruited a total of 452 patients were included. The rates of conversion from LA to open surgery ranged from 0%-41.3%. The meta-analysis revealed that LA for PIs is associated with reduced length of hospital stay (weighted mean difference, -5.64; 95% confidence interval [CI], -7.11 to -4.16; P < 0.00001). No significant difference was observed between LA and open surgery in terms of operation time (weighted mean difference, 2.57; 95% CI, -10.91 to 16.05; P = 0.71), postoperative mortality, overall morbidity (odds ratio [OR], 0.64; 95% CI, 0.35-1.17; P = 0.14], incidence of pancreatic fistula (OR, 0.86; 95% CI, 0.51-1.44; P = 0.56), and recurrence of hyperglycemia (OR, 1.81; 95% CI, 0.41-7.95; P = 0.43). CONCLUSIONS Laparoscopic treatment for PIs is a safe and feasible approach associated with reduction in length of hospital stay and comparable rates of postoperative complications in relation with open surgery.

Surgical treatment and clinical outcome of nonfunctional pancreatic neuroendocrine tumors: a 14-year experience from one single center.

AbstractOur primary aim of the present study was to analyze the clinical characteristics and surgical outcome of nonfunctional pancreatic neuroendocrine tumors (non-F-P-NETs), with an emphasis on evaluating the prognostic value of the newly updated 2010 grading classification of the World Health Organization (WHO).Data of 55 consecutive patients who were surgically treated and pathologically diagnosed as non-F-P-NETs in our single institution from January 2000 to December 2013 were retrospectively collected.This entirety comprised of 55 patients (31 males and 24 females), with a mean age of 51.24 ± 12.95 years. Manifestations of non-F-P-NETs were nonspecific. Distal pancreatectomy, pancreaticoduodenectomy, and local resection of pancreatic tumor were the most frequent surgical procedures, while pancreatic fistula was the most common but acceptable complication (30.3%). The overall 5-year survival rate of this entire cohort was 41.0%, with a median survival time of 60.4 months. Patients who underwent R0 resections obtained a better survival than those who did not (P < 0.005). As for the prognostic analysis, tumor size and lymph invasion were only statistically significant in univariate analysis (P = 0.046 and P < 0.05, respectively), whereas the newly updated 2010 grading classification of WHO (G1 and G2 vs G3), distant metastasis, and surgical margin were all meaningful in both univariate and multivariate analysis (P = 0.045, 0.001, and 0.042, respectively).Non-F-P-NETs are a kind of rare neoplasm, with mostly indolent malignancy. Patients with non-F-P-NETs could benefit from the radical resections. The new WHO criteria, distant metastasis and surgical margin, might be independent predictors for the prognosis of non-F-P-NETs.

Triple-layer duct-to-mucosa pancreaticojejunostomy with resection of jejunal serosa decreased pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). We described a new method of pancreaticojejunostomy (PJ) developed by combining triple-layer duct-to-mucosa PJ with resection of jejunal serosa, which was named as modified layer-to-layer PJ (MLLPJ). The aim of the present study was to observe whether the new technique would effectively reduce the PF rate in comparison with two-layer duct-to-mucosa PJ (TLPJ). METHODS Data on 184 consecutive patients who underwent the two methods of PJ after standard PD between January 1, 2010 and January 31, 2013 were collected retrospectively from a prospective database. The primary endpoint was the PF rate. The risk factors of PF were investigated by using univariate and multivariate analyses. RESULTS A total of 88 patients received TLPJ and 96 underwent MLLPJ. Rate of PF for the entire cohort was 8.2%. There were 11 fistulas (12.5%) in the TLPJ group and four fistulas (4.2%) in the MLLPJ group (P = 0.039). Body mass index, pancreatic texture, pancreatic duct diameter, and methods of PJ anastomosis had significant effects on the formation of PF on univariate analysis. Multivariate analysis showed that pancreatic duct diameter ≤3 mm and TLPJ were the significant risk factors of PF. CONCLUSIONS MLLPJ effectively reduces the PF rate after PD in comparison with TLPJ. Results confirm increased PF rates in patients with pancreatic duct diameter ≤3 mm compared with pancreatic duct diameter >3 mm.

Regulating the expression of CD80/CD86 on dendritic cells to induce immune tolerance after xeno-islet transplantation

BACKGROUND Antigen present cells (APCs) have been demonstrated to play dual roles in immune tolerance. Recently, compelling evidence indicates that APCs that express CD80, but not CD86 can protect allograft. We investigated whether modulation of CD80 in dendritic cells (DCs) offer protection for xeno-islets. METHODS In vitro, isolated mature murine DCs received untransfection, transfection with CD86 siRNA or negative control siRNA. The DCs were used in mixed lymphocyte reaction in which rat islets and murine splenocytes were further added. On day 3 of co-culturing, the proliferation of lymphocytes was measured and interleukin (IL)-2, IL-4, IL-10, transforming growth factor β (TGF-β), interferon γ (INF-γ) and indoleamine 2,3-dioxygenase (IDO) from the supernatants were determined. Islets viability and function were also assessed. In vivo, streptozotocin-induced diabetic mice underwent rat islets transplantation were pre-treated with above DCs. At designated time, xeno-islets were subjected to histopathology, immunohistochemistry, survival time and functional tests. Peripheral blood T lymphocyte profiles were also examined. RESULTS CD86-silenced-DCs had unchanged expression of CD80 and significantly suppressed the proliferation of lymphocytes. CD86-silenced-DCs simultaneously reduced IL-2 and INF-γ and increased IL-10, TGF-β and IDO, while had minimal effect on IL-4. The CD86-silenced-DCs also improved cell viability and function of xeno-islets when compared to untransfection and transfection control groups. In xeno-islets transplanted diabetic mice, transfer of CD86-silenced-DCs resulted in improved histopathology and dramatically prolonged survival time of the islets. These effects were also mirrored by the functional tests. Further analysis revealed that CD86-silenced-DCs had up-regulated levels of CD4(+)CD25(+)T cells in the peripheral blood compared to the other groups. CONCLUSIONS CD86-silenced-DCs induced immune tolerance of rat xeno-islets in recipient diabetic mice with up-regulated peripheral blood CD4(+)CD25(+)T cells.

Pancreatic Castleman’s Disease: Studies of Three Cases And A Cumulative Review of the Literature

Castleman’s disease (CD) is a relatively rare and benign disorder. Pancreatic localization of CD is even more rare and is usually indistinguishable from pancreatic neoplasms. We report three cases of CD in which pancreas was all involved. One located in the tail of the pancreas, who accepted distal pancreatectomy, and the others in the head accepted enucleation. In addition, we review current data on its pathogenesis, imaging findings, diagnosis, differential diagnosis, and treatment.

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding

BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB. METHODS The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014. RESULTS A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED. CONCLUSION For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

Epidemiology, diagnosis, surgical treatment and prognosis of the pancreatic neuroendocrine tumors: Report of 125 patients from one single center

OBJECTIVE The objective of the following study is to summarize the epidemiology of pancreatic neuroendocrine tumors (p-NETs) in our single institution, analyze the diagnostic characteristics, share the experience of surgical treatments and discuss the prognostic factors. METHODS A retrospective collection and analysis of clinical data of 125 patients with p-NETs which were pathologically confirmed in our hospital from January 2002 to December 2012. RESULTS A total of 125 patients of which 52 were males and 73 were females. Totally 92 patients had functional p-NETs, while non-functional p-NETs were diagnosed in 33 patients. The most common operative procedures performed were local resection of pancreatic tumor (47.2%), followed by distal pancreatectomy (29.6%). Thirty patients (28%) had post-operative complications, the most common of which was pancreatic fistula (22.4%). The overall survival rate at 5 years was 68.4%. The 5-year survival rate for patients with functional tumors was 75.1%, compared with 50.0% for those with non-functional tumors (P = 0.021). The survival time of patients with R0 resection was statistically longer than that of patients with Not R0 resection (P < 0.005). In univariate analysis, the most powerful predictors of poor outcome were gender, age, tumor size, functional status, surgical margins, lymph node invasion and distant metastasis. However only surgical margin and distant metastasis were significant predictors in multivariate analysis (P = 0.001, 0.047, respectively). CONCLUSION p-NETs are an uncommon and heterogeneous group of tumors, with a rising incidence. Surgery is the most effective treatment. Surgical margin and distant metastasis were the most significant prognostic factors. Radical resection should be taken more into considerations.