Quality of life after pancreatic surgery

BACKGROUND Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas.Increasing attention has been paid to changes in quality of life(QOL)after pancreatic surgery.AIM To summarize and analyze current research results on QOL after pancreatic surgery.METHODS A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Relevant studies were identified by screening the references of retrieved articles.Studies on patients’QOL after pancreatic surgery published after January 1,2012,were included.These included prospective and retrospective studies on patients'QOL after several types of pancreatic surgeries.The results of these primary studies were summarized inductively.RESULTS A total of 45 articles were included in the study,of which 13 were related to pancreaticoduodenectomy(PD),seven to duodenum-preserving pancreatic head resection(DPPHR),nine to distal pancreatectomy(DP),two to central pancre-atectomy(CP),and 14 to total pancreatectomy(TP).Some studies showed that 3-6 months were needed for QOL recovery after PD,whereas others showed that 6-12 months was more accurate.Although TP and PD had similar influences on QOL,patients needed longer to recover to preoperative or baseline levels after TP.The QOL was better after DPPHR than PD.However,the superiority of the QOL between patients who underwent CP and PD remains controversial.The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL.Minimally invasive surgery could improve patients’QOL in the early Core Tip:This review summarizes and analyzes current research results on quality of life(QOL)after pancreatic surgery.The article covers the discussion and analysis of the QOL of various pancreatic surgeries.Which kind of surgical procedure has better QOL is controversial.The long-term benefits on QOL of minimally invasive surgery over open surgery are contro-INTRODUCTION The pancreas,located in the retroperitoneum,is a glandular organ with endocrine and exocrine functions.It can be divided into four main parts:Head,neck,body,and tail.Pancreatic surgery can be divided into pancreaticoduoden-ectomy(PD),duodenum-preserving pancreatic head resection(DPPHR),distal pancreatectomy(DP),central pancre-atectomy(CP),and total pancreatectomy(TP).Pancreatic surgery is challenging due to the organ’s complex anatomical structure,peripheral vascularity,and intractable postoperative complications.Following the standardization of surgical steps and improvements in relevant medical techniques and surgical instruments,the safety of pancreatic surgery has significantly improved.Perioperative morbidity,mortality,and other related indicators have become more acceptable.However,owing to the organ’s essential role in digestion,absorption,and blood glucose regulation,changes in the quality of life(QOL)of patients after pancreatic surgery have attracted the attention of surgeons.More patients with non-malignant pancreatic diseases are willing to undergo surgical treatment because of the acceptable safety.In this case,from the perspective of the patient postoperatively,the significance of rehabilitation reflects the traditional perioperative outcome and QOL[1].The QOL is a new concept that extends beyond health.Although there is no consensus on its conception[2],we can consider it a multi-dimensional architecture that incorporates objective and individual subjective views of aspects of one’s physical,psychological,and social well-being[3-5].It includes evaluating physical health,and many subscales,such as emotion,job,culture,family,sociability,economy,cognition,happiness,sex,and some symptoms[6].Since people have realized the importance of QOL,many QOL scales have emerged,including the European Organization for Research and Treatment of Cancer QLQ-C30,European Quality of Life 5-dimension,36-item Short,etc.However,it is challenging to follow up on patients’QOL once they are discharged from the hospital.Consequently,most relevant studies had small sample sizes or lacked long-term follow-up results.Moreover,a summary of studies on QOL after pancreatic surgery is lacking.This study assessed the QOL in patients who underwent PD,DPPHR,DP,CP and TP.We conducted this study to describe the existing findings on the QOL after pancreatic surgery to make it easier for surgeons and patients to decide on a surgical approach.In addition,we attempted to identify controversial results to encourage further targeted research.

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

Subdiaphragmatic abscess caused by the recently identifi ed pathogen Cutibacterium modestum: a case report

Subdiaphragmatic abscess is uncommon in patients who undergo resection for hepatocellular carcinoma.The identifi cation of pathogens and appropriate treatment can be challenging.[1]Herein,we present a case of subdiaphragmatic abscess caused by Cutibacterium modestum.A 66-year-old man was admitted to our hospital with fever,cough,and persistent,dull pain in the right upper quadrant for two days.The patient’s medical history included liver cirrhosis,radical resection of hepatocellular carcinoma three months prior to admission,and type 2 diabetes mellitus.Physical examination revealed tachycardia with small moist rales in the right lower chest.Abdominal examination revealed an L-shaped,well-healed surgical incision in the right upper quadrant without intra-abdominal mass or tenderness.

Assessment of early factors for identification or prediction severe acute pancreatitis in pregnancy

BACKGROUND Acute pancreatitis in pregnancy(APIP)is a rare and serious condition,and severe APIP(SAPIP)can lead to pancreatic necrosis,abscess,multiple organ dysfunction,and other adverse maternal and infant outcomes.Therefore,early identification or prediction of SAPIP is important.AIM To assess factors for early identification or prediction of SAPIP.METHODS The clinical data of patients with APIP were retrospectively analyzed.Patients were classified with mild acute pancreatitis or severe acute pancreatitis,and the clinical characteristics and laboratory biochemical indexes were compared between the two groups.Logical regression and receiver operating characteristic curve analyses were performed to assess the efficacy of the factors for identification or prediction of SAPIP.RESULTS A total of 45 APIP patients were enrolled.Compared with the mild acute pancreatitis group,the severe acute pancreatitis group had significantly increased(P<0.01)heart rate(HR),hemoglobin,neutrophil ratio(NEUT%),and neutrophil–lymphocyte ratio(NLR),while lymphocytes were significantly decreased(P<0.01).Logical regression analysis showed that HR,NEUT%,NLR,and lymphocyte count differed significantly(P<0.01)between the groups.These may be factors for early identification or prediction of SAPIP.The area under the curve of HR,NEUT%,NLR,and lymphocyte count in the receiver operating characteristic curve analysis was 0.748,0.732,0.821,and 0.774,respectively.The combined analysis showed that the area under the curve,sensitivity,and specificity were 0.869,90.5%,and 70.8%,respectively.CONCLUSION HR,NEUT%,NLR,and lymphocyte count can be used for early identification or prediction of SAPIP,and the combination of the four factors is expected to improve identification or prediction of SAPIP.

Treatment of choice for malignant gastric outlet obstruction: More than clearing the road

In this editorial,we comment on the in-press article in the World Journal of Gas-trointestinal Endoscopy concerning the treatment of malignant gastric outlet obstruction(mGOO).The original theory of treatment involves bypassing the obstruction or reenabling the patency of the passage.Conventional surgical gastroenterostomy provides long-term relief of symptoms in selected patients,with substantial morbidity and a considerable rate of delayed gastric emptying.Endoscopic stenting was introduced as an alternative minimally invasive proce-dure with less procedural morbidity and rapid clinical improvement;however,it presented a high rate of long-term recurrence.Therefore,challenges remain in the treatment of mGOO patients to improve clinical outcomes.Endoscopic ultra-sound-guided gastroenterostomy has recently emerged as a promising method because of the combined effects of surgery and endoscopy,whereas stomach-partitioning gastrojejunostomy has been reported as a modified surgical proce-dure to reduce the rate of delayed gastric emptying.In decision-making regarding the treatment of choice,it should be taken into account that mGOO might be accompanied by a variety of pathological conditions,including cancer cachexia,anorexia,malabsorption,and etc.,all of which can also lead to the characteristic symptoms and poor nutritional status of mGOO.The treatment plan should consider comprehensive aspects of patients to achieve practical improve-ments in prognosis and the quality of life.

ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer

Background: ADAMTS(a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma(PDAC). Methods: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition(EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction(q PCR) and Western blotting. Results: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. Conclusions: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.

Role of intelligent/interactive qualitative and quantitative analysisthree-dimensional estimated model in donor-recipient size mismatch following deceased donor liver transplantation

BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

Relationships between Chronic Diseases and Depression among Middleaged and Elderly People in China: A Prospective Study from CHARLS

Given the rapid increase in the prevalence of chronic diseases in aging populations,this prospective study including 17707 adults aged≥45 years from China Health and Retirement Longitudinal Study was used to estimate the associations between chronic discase,multimorbidity,and depression among middle-aged and elderly adults in China,and explore the mediating factors.Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale(CES-D-10)questionnaire.Twelve chronic physical conditions,including hypertension,diabetes,dyslipidemia,cancer,chronic lung disease,liver disease,heart failure,stroke,kidney disease,arthritis or rheumatism,asthma,digestive disease were assessed.The prevalence rates for physical multimorbidity and depression(CES-D-10≥10)were 43.23%and 36.62%,respectively.Through multivariable logistic models and generalized estimating equation(GEE)models,we found all 12 chronic physical conditions,and multimorbidity were significantly associated with depression.Both mobility problems and chronic pain explained more than 30%of the association for all chronic conditions,with particularly high percentages for stroke(51.56%)and cancer(51.06%)in mobility problems and cancer(53.35%)in chronic pain.Limited activities of daily living(ADL)explained 34.60%of the stroke-cancer relationship,while sleep problems explained between 10.15%(stroke)and 14.89%(chronic lung disease)of the association.Individuals with chronic diseases or multimorbidity are significantly more likely to be depressed.Functional symptoms involving limitations of ADL and mobility difficulties mediated much of the association between chronic diseases and incident depression.These symptoms could be targeted for interventions to ameliorate the incidence of depression among individuals with chronic conditions.

Combined Hangzhou criteria with neutrophillymphocyte ratio is superior to other criteria in selecting liver transplantation candidates with HBV-related hepatocellular carcinoma

BACKGROUND： The elevation of neutrophil-lymphocyte ratio （NLR） has adverse effects on the prognosis of patients with hepatocellular carcinoma （HCC） who have received liver transplantation （LT）. The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou crite- ria for selecting HCC patients for LT.

CD133^+ gallbladder carcinoma cells exhibit self-renewal ability and tumorigenicity

AIM： To identify cancer stern cells （CSCs） in human gallbladder carcinomas （GBCs）. METHODS： Primary GBC cells were cultured under serum-free conditions to produce floating spheres. The stem-cell properties of the sphere-forming cells, including self-renewal, differentiation potential, chemoresistance and tumorigenicity, were determined in vitro or in vivo. Cell surface expression of CD133 was investigated in primary tumors and in spheroid cells using flow cytometry. The sphere-colony-formation ability and tumorigenicity of CD133＋ cells were assayed.floating spheroids were generated from primary GBC cells, and these sphere-forming cells could generate new progeny spheroids in serum-free media. Spheroid cells were differentiated under serum-containing conditions with downregulation of the stem cell markers Oct-4, Nanog, and nestin （P 〈 0.05）. The differentiated cells showed lower spheroid-colony-formation ability than the original spheroid cells （P 〈 0.05）. Spheroid ceils were more resistant to chemotherapeutic reagents than the congenetic adherent cells （P 〈 0.05）. Flow cytometry showed enriched CD133＋ population in sphereforming cells （P 〈 0.05）. CD133＋ cells possessed high colony-formation ability than the CD133 population （P 〈 0.01）. CD133＋ cells injected into nude mice revealed higher tumorigenicity than their antigen-negative counterparts （P 〈 0.05）. CONCLUSION： CD133 may be a cell surface marker for CSCs in GBC.

Feasibility and safety of single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy in an ambulatory setting

Background: Single-incision laparoscopic surgery has emerged as an alternative to conventional laparoscopic cholecystectomy(LC) in the clinical setting. Limited information is available on the possibility of performing single-incision laparoscopic surgery as an ambulatory procedure. This study aimed to determine the feasibility and safety of single-incision laparoscopic cholecystectomy(SILC) versus conventional LC in an ambulatory setting. Methods: Ninety-one patients were randomized to SILC( n = 49) or LC( n = 42). The success rate, operative duration, blood loss, hospital stay, gallbladder perforation, drainage, delayed discharge, readmission, total cost, complications, pain score, vomiting, and cosmetic satisfaction of the two groups were then compared. Results: There were significant differences in the operative time(46.89 ± 10.03 min in SILC vs. 37.24 ± 10.23 min in LC;P < 0.001). As compared with LC, SILC was associated with lower total costs(8012.28 ± 752.67 RMB vs. 10258.91 ± 1087.63 RMB;P < 0.001) and better cosmetic satisfaction(4.94 ±0.24 vs. 4.74 ± 0.54;P = 0.031). There were no significant differences between-group in terms of general data, success rate, blood loss, hospital stay, gallbladder perforation, drainage, delayed discharge, readmission, complications, pain score, and vomiting( P > 0.05). Conclusions: Ambulatory SILC is safe and feasible for selected patients. The advantages of SILC as compared with LC are improved cosmetic satisfaction and lower total costs.

Impact of Percutaneous Transhepatic Biliary Drainage on Clinical Outcomes of Patients with Malignant Obstructive Jaundice Undergoing Laparoscopic Pancreaticoduodenectomy

Preoperative biliary drainage may increase the morbidity and mortality of pancreatico-duodenectomy.Studies on percutaneous transhepatic biliary drainage(PTBD)before laparoscopic pancreaticoduodenectomy(LPD),however,are scarce.The aim of this study was to examine the impact of PTBD on clinical outcomes of patients with malignant obstructive jaundice undergoing LPD.Clinical data of 172 patients who had malignant obstructive jaundice and underwent LPD from 2014 to 2017 in our hospital were retrospectively analyzed.Demographics,catheterrelated complications,postoperative complications,and oncological outcormes were collected and analyzed.Propensity score matching was performed to minimize selection bias associated with the comparison of data between patients who underwent PTBD and then LPD(PTBD group),and those given LPD alone(LPD group).The results showed that,in the PTBD group relative to the LPD group,the operating time was significantly shortened(250.28±69.95 vs.278.58±86.51 min,P=0.0196),the intraopcrative blood loss was markedly reduced(271.96±403.47 vs.429.72±482.47 mL,P=0.022),and overall rates of complications(16.33%vs.36.49%,P=0.0025)including postoperative haemorrhage(2.04%vs.12.16%,P=0.0072)and delayed gastric emptying(4.08% vs.13.51%,P=0.0251)were greatly decreased.The propensity score-matched analysis,with 48 patients enrolled in each group,revealed no statistically significant differences in operating duration(262.71±68.64 vs.280.25±83.52 min,P=0.264),intraoperative blood loss(290.21±407.71 vs.373.75±422.33 mL,P=0.327)and delayed gastric emptying(4.17% vs.12.50%,P=0.1396).PTBD group had lower incidences in overall complications(22.92% vs.39.58%,P=0.0481)and postoperative haemorrhage(2.08% vs.12.50%,P=0.0497)than LPD group.In conclusion,patients with malignant obstructive jaundice may benefit from PTBD procedure before LPD in terms of perioperative outcomes.

Circulating myeloid-derived suppressor cells in patients with pancreatic cancer

BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS： Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells （PBMCs） to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor （GM-CSF） and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS： CD14＋/CD11b＋/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS： MDSCs were tumor related： tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14＋/CD11b＋/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

Study on acute recent stage pancreatitis

Acute pancreatitis(AP)is an inflammatory disease of the pancreas which involves the pancreas and surrounding tissue,and systemic inflammation with a characteristic systemic increase of vascular permeability and increased risk of multiple organ dysfunction.Currently,the pathogenesis of AP is fuzzy,and the diagnosis and treatment need to be standardized.Nevertheless,increased knowledge of AP may achieve more thorough understanding of the pathogenesis.The use of further advanced diagnostic tools and superior treatment,potentially will help clinicians to manage AP at an appropriate stage.However,in view of the multi factorial disease and the complex clinical manifestations,the management of patients with AP is also remaining areas for improvement.

Clinical significance of programmed death 1/programmed death ligand 1 pathway in gastric neuroendocrine carcinomas

BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.

mi R-1181 inhibits invasion and proliferation via STAT3 in pancreatic cancer

AIM To examine the role of microRNA 1181 (miR-1181) in invasion and proliferation in pancreatic cancer. METHODS We analyzed the expression of miR-1181 in several pancreatic cancer cell lines and generated stable MIA- PaCa- 2 and PANC-1 cell lines with up-regulated miR-1181 expression using an adenovirus delivery system. We then investigated miR-1181 ' s effect on invasion and proliferation of pancreatic cancer cells by transwell assay, wound healing assay, cell counting kit-8 assay and colony-forming assay, and explored any underlying mechanisms by western bolt. Beyond that, we observed the change of the PANC-1 cell ' s cytoskeleton by immunofluorescence staining. RESULTS Our data showed that miR-1181 was relatively downregulated in pancreatic cancer cell lines compared with normal pancreatic ductal epithelial cells. And miR-1181 inhibited the migration, invasion and proliferation activities of MIA-PaCa-2 and PANC-1 cells. Notably,after over-expressing of miR-1181 in PANC-1 cells, F-actin depolymerized. Immunofluorescence staining shows decreased F-actin and beta-tubulin expression in PANC-1 cells over-expressing miR- 1181 compared with the control cells. Furthermore, we found that over-expressing miR- 1181 inhibited the expression of signal transducer and activator of transcription 3(STAT3) while knocking- down miR-1181 up-regulated the expression of STAT3. Knocking-down miR-1181 promoted the invasion and proliferation of pancreatic cancer cells. And inhibition of STAT3 blocked the promotion effects of knocking- down miR-1181 on proliferation and invasion in pancreatic cancer. CONCLUSION Together our findings suggest that miR-1181 may be involved in pancreatic cancer cell invasion and proliferation by targeting STAT3 and indicate that miR-1181 may be a potential therapeutic agent for pancreatic cancer.

Side Population Cells in Human Gallbladder Cancer Cell Line GBC-SD Regulated by TGF-β-induced Epithelial-mesenchymal Transition

Mounting evidence has shown that side population （SP） cells are enriched for cancer stem cells （CSCs） responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-β （TGF-β）-induced epithelial-mesenchymal transition （EMT）, and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-β and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-β. In conclusion, TGF-β-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-β-induced EMT may provide a novel strategy for preventing cancer progression.

Construction of a lentiviral vector for RNA interference of human VIM gene and its silencing effect in pancreatic cancer cells

Objective： To construct a lentiviral expression vector for RNA interference （RNAi） of human VIM gene; and assess its gene silencing effect in pancreatic cancer cell line Panc-1. Methods： Three pairs of human VIM gene short hairpin RNA（shRNA） sequences were designed using a software available on-line and one pair came from document. After synthesis and annealing, four double-stranded oligonucleotides （dsOligo） were cloned into the pGCL-GFP/U6 plasmid, which were subsequently confirmed by polymerase chain reaction （PCR） and DNA sequencing analysis. Real-time PCR and Westemblotting were used to screen the effective pGCL-GFP-shRNA plasmid in 293T cells, then the most effective one was packed into the recombinant lentivirus Lv-VIM-shRNA with lentiviral packing materials pHelper 1.0 and pHelper 2.0 in 293T cells. The titer of lentivirus was determined by hole-by-dilution titer assay. The silencing effect of Lv-VIM-shRNA in Panc-1 calls were validated by real-time PCR and Western-blotting. Results： An effective Lv-VIM-shRNA was successfully constructed. The titer of lentivirus was determined on 2× 10^9TU/mL. The expressions of VIM mRNA and vimentin were down-regluated in the Panc-1 cells infected with Lv-VIM-shRNA. Conclusion： An effective Lv-VIM-shRNA could inhibit the expression of VIM gene in Panc-1 cells in vitro, which provides a tool for investigating the role of VIM gene in the signaling pathway involved in tumorigenesis and progression of pancreatic cancer and searching new therapeutic targets.

Expression and Significance of HIF-1α and HIF-2α in Pancreatic Cancer

Summary： The expression levels of hypoxia-inducible factor lalpha （HIF-lct） and HIF-2a in pancreatic cancer （PC） and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1 α and HIF-2α mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1 α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α mRNA was up-regulated in most cancer tis- sues （P〈0.05）. HIF-1α staining was weakly positive in most cancer tissues and strongly positive in ad- jacent pancreas tissues （P〈0.05）. Clinicopathologic analysis revealed that relatively strong HIF-1α ex- pression in cancer tissues was related to greater invasion （P〈0.05）, higher tumor pathologic stage （P〈0.05）, higher American Joint Committee on Cancer （AJCC） stage （P〈0.05） and shorter overall sur- vival time （P〈0.05）. Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion （P〈0.05）, lower tumor pathologic stage （P〈0.05）, lower AJCC stage （P〈0.05） and longer overall survival time （P〈0.05）. Moreover, the HIF-1αhigh/HIF-2αlow group showed a shorter survival time than the HIF-1αlow/HIF-2αhigh group. In con- clusion, although HIF-1α and HIF-2α mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.

Mutual regulation between microRNA-373 and methyl-CpGbinding domain protein 2 in hilar cholangiocarcinoma

AIM:To investigate the reciprocal modulation between microRNA(miRNA) and DNA methylation via exploring the correlation between miR-373 and methyl-CpGbinding domain protein(MBD)2.METHODS:MiR-373 expression was examined using the TaqMan miRNA assay.Methylation of miR-373 was investigated using methylation-specific polymerase chain reaction,and recruitment of methyl binding proteins was studied using the chromatin immunoprecipitation assay.Mutation analysis was conducted using the QuikChange Site-Directed Mutagenesis kit.The activity of miR-373 gene promoter constructs and targeting at MBD2-three prime untranslated region(3'UTR) by miR-373 were evaluated by a dual-luciferase reporter gene assay.RESULTS:In hilar cholangiocarcinoma,miR-373 decreased and was closely associated with poor cell differentiation,advanced clinical stage,and shorter survival.The promoter-associated CpG island of miR-373 gene was hypermethylated and inhibited expression of miR-373.MBD2 was up-regulated and enriched at the promoter-associated CpG island of miR-373.Methylation-mediated suppression of miR-373 required MBD2 enrichment at the promoter-associated CpG island,and miR-373 negatively regulated MBD2 expression through targeting the 3'UTR.CONCLUSION:MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2 activity through a feedback loop of CpG island methylation.