Exploring the landscape of minimally invasive pancreatic surgery: Progress, challenges, and future directions

Minimally invasive surgery(MI)has become the standard of care for many surgical procedures aimed at reducing the burden on patients.However,its adoption in pancreatic surgery(PS)has been limited by the pancreas’s unique location and the complexity of the dissection and reconstruction phases.These factors continue to contribute to PS having one of the highest morbidity and mortality rates in general surgery.Despite a rough start,MIPS has gained widespread acceptance in clinical practice recently.Robust evidence supports MI distal pancreatectomy safety,even in oncological cases,indicating its potential superiority over open surgery.However,definitive evidence of MI pancre-aticoduodenectomy(MIPD)feasibility and safety,particularly for malignant lesions,is still lacking.Nonetheless,reports from high-volume centers are emer-ging,suggesting outcomes comparable to those of the open approach.The robotic PS increasing adoption,facilitated by the wider availability of robotic platforms,may further facilitate the transition to MIPD by overcoming the technical con-straints associated with laparoscopy and accelerating the learning curve.Alth-ough the MIPS implementation process cannot be stopped in this evolving world,ensuring patient safety through strict outcome monitoring is critical.Investing in younger surgeons with structured and recognized training programs can promote safe expansion.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.

Unraveling the enigma:A comprehensive review of solid pseudopapillary tumor of the pancreas

Solid pseudopapillary tumor of the pancreas(SPTP)is a rare neoplasm predom-inantly observed in young females.Pathologically,CTNNB1 mutations,β-catenin nuclear accumulation,and subsequent Wnt-signaling pathway activation are the leading molecular features.Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies.Surgical resection remains the mainstay treatment.Risk models,such as the Fudan Prognostic Index,show promise as predictive tools for assessing the prognosis of SPTP.Establishing three types of metachronous liver metastasis can be beneficial in tailoring individu-alized treatment and follow-up strategies.Despite advancements,challenges persist in understanding its etiology,establishing standardized treatments for unresectable or metastatic diseases,and developing a widely recognized grading system.This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology,clinical presentation,pathology,molecular characteristics,diagnostic methods,treatment options,and prognostic factors.

Optimizing prediction models for pancreatic fistula after pancreatectomy:Current status and future perspectives

Postoperative pancreatic fistula(POPF)is a frequent complication after pancre-atectomy,leading to increased morbidity and mortality.Optimizing prediction models for POPF has emerged as a critical focus in surgical research.Although over sixty models following pancreaticoduodenectomy,predominantly reliant on a variety of clinical,surgical,and radiological parameters,have been documented,their predictive accuracy remains suboptimal in external validation and across diverse populations.As models after distal pancreatectomy continue to be pro-gressively reported,their external validation is eagerly anticipated.Conversely,POPF prediction after central pancreatectomy is in its nascent stage,warranting urgent need for further development and validation.The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance.Moreover,there is potential for the development of personalized prediction models based on patient-or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF.In the future,prospective multicenter studies and the integration of novel imaging technologies,such as artificial intelligence-based radiomics,may further refine predictive models.Addressing these issues is anticipated to revolutionize risk stratification,clinical decision-making,and postoperative management in patients undergoing pancre-atectomy.

Identifying the risk factors for pancreatic fistula after laparoscopic pancreaticoduodenectomy in patients with pancreatic cancer

BACKGROUND Laparoscopic pancreaticoduodenectomy(LPD)is a surgical procedure for treating pancreatic cancer;however,the risk of complications remains high owing to the wide range of organs involved during the surgery and the difficulty of anastomosis.Pancreatic fistula(PF)is a major complication that not only increases the risk of postoperative infection and abdominal hemorrhage but may also cause multi-organ failure,which is a serious threat to the patient’s life.This study hypothesized the risk factors for PF after LPD.AIM To identify the risk factors for PF after laparoscopic pancreatoduodenectomy in patients with pancreatic cancer.METHODS We retrospectively analyzed the data of 201 patients admitted to the Fudan University Shanghai Cancer Center between August 2022 and August 2023 who underwent LPD for pancreatic cancer.On the basis of the PF’s incidence(grades B and C),patients were categorized into the PF(n=15)and non-PF groups(n=186).Differences in general data,preoperative laboratory indicators,and surgery-related factors between the two groups were compared and analyzed using multifactorial logistic regression and receiver-operating characteristic(ROC)curve analyses.RESULTS The proportions of males,combined hypertension,soft pancreatic texture,and pancreatic duct diameter≤3 mm;surgery time;body mass index(BMI);and amylase(Am)level in the drainage fluid on the first postoperative day(Am>1069 U/L)were greater in the PF group than in the non-PF group(P<0.05),whereas the preoperative monocyte count in the PF group was lower than that in the non-PF group(all P<0.05).The logistic regression analysis revealed that BMI>24.91 kg/m²[odds ratio(OR)=13.978,95%confidence interval(CI):1.886-103.581],hypertension(OR=8.484,95%CI:1.22-58.994),soft pancreatic texture(OR=42.015,95%CI:5.698-309.782),and operation time>414 min(OR=15.41,95%CI:1.63-145.674)were risk factors for the development of PF after LPD for pancreatic cancer(all P<0.05).The areas under the ROC curve for BMI,hypertension,soft pancreatic texture,and time prediction of PF surgery were 0.655,0.661,0.873,and 0.758,respectively.CONCLUSION BMI(>24.91 kg/m²),hypertension,soft pancreatic texture,and operation time(>414 min)are considered to be the risk factors for postoperative PF.

Recurrence scoring system predicting early recurrence for patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy and portomesenteric vein resection

BACKGROUND Pancreatectomy with concomitant portomesenteric vein resection(PVR)enables patients with portomesenteric vein(PV)involvement to achieve radical resection of pancreatic ductal adenocarcinoma,however,early recurrence(ER)is frequently observed.AIM To predict ER and identify patients at high risk of ER for individualized therapy.METHODS Totally 238 patients undergoing pancreatectomy and PVR were retrospectively enrolled and were allocated to the training or validating cohort.Univariate Cox and LASSO regression analyses were performed to construct serum recurrence score(SRS)based on 26 serum-derived parameters.Uni-and multivariate Cox regression analyses of SRS and 18 clinicopathological variables were performed to establish a Nomogram.Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy.Survival analysis was performed using Kaplan-Meier method and log-rank test.RESULTS Independent serum-derived recurrence-relevant factors of LASSO regression model,including postoperative carbohydrate antigen 19-9,postoperative carcinoembryonic antigen,postoperative carbohydrate antigen 125,preoperative albumin(ALB),preoperative platelet to ALB ratio,and postoperative platelets to lymphocytes ratio,were used to construct SRS[area under the curve(AUC):0.855,95%CI:0.786–0.924].Independent risk factors of recurrence,including SRS[hazard ratio(HR):1.688,95%CI:1.075-2.652],pain(HR:1.653,95%CI:1.052-2.598),perineural invasion(HR:2.070,95%CI:0.827-5.182),and PV invasion(HR:1.603,95%CI:1.063-2.417),were used to establish the recurrence nomogram(AUC:0.869,95%CI:0.803-0.934).Patients with either SRS>0.53 or recurrence nomogram score>4.23 were considered at high risk for ER,and had poor long-term outcomes.CONCLUSION The recurrence scoring system unique for pancreatectomy and PVR,will help clinicians in predicting recurrence efficiently and identifying patients at high risk of ER for individualized therapy.

Current status and progress of pancreatic cancer in China

Cancer is currently one of the most important public health problems in the world.Pancreatic cancer is a fatal disease with poor prognosis.As in most other countries,the health burden of pancreatic cancer in China is increasing,with annual mortality rates almost equal to incidence rates.The increasing trend of pancreatic cancer incidence is more significant in the rural areas than in the urban areas.Annual diagnoses and deaths of pancreatic cancer in China are now beyond the number of cases in the United States.GLOBOCAN 2012 estimates that cases in China account for 19.45%(65727/337872) of all newly diagnosed pancreatic cancer and 19.27%(63662/330391) of all deaths from pancreatic cancer worldwide.The population's growing socioeconomic status contributes to the rapid increase of China's proportional contribution to global rates.Here,we present an overview of control programs for pancreatic cancer in China focusing on prevention,early diagnosis and treatment.In addition,we describe key epidemiological,demographic,and socioeconomic differences between China and developed countries.Facts including no nationwide screening program for pancreatic cancer,delay in early detection resulting in a late stage at presentation,lack of awareness of pancreatic cancer in the Chinese population,and low investment compared with other cancer types by government have led to backwardness in China's pancreatic cancer diagnosis and treatment.Finally,we suggest measures to improve health outcomes of pancreatic cancer patients in China.

Outcome and costs of laparoscopic pancreaticoduodenectomy during the initial learning curve vs laparotomy

AIM:To compare laparoscopic pancreaticoduodenectomy(TLPD) during the initial learning curve with open pancreaticoduodenectomy in terms of outcome and costs.METHODS:This is a retrospective review of the consecutive patients who underwent TLPD between December 2009 and April 2014 at our institution.The experiences of the initial 15 consecutive TLPD cases,considered as the initial learning curve of each surgeon,were compared with the same number of consecutive laparotomy cases with the same spectrum of diseases in terms of outcome and costs.Laparoscopic patients with conversion to open surgery were excluded.Preoperative demographic and comorbidity data were obtained.Postoperative data on intestinal movement,pain score,mortality,complications,and costs were obtained for analysis.Complications related to surgery included pneumonia, intra-abdominal abscess,postpancreatectomy hemorrhage,biliary leak,pancreatic fistula,delayed gastric emptying,and multiple organ dysfunction syndrome.The total costs consisted of cost of surgery,anesthesia,and admission examination.RESULTS:A total of 60 patients,including 30 consecutive laparoscopic cases and 30 consecutive open cases,were enrolled for review.Demographic and comorbidity characteristics of the two groups were similar.TLPD required a significantly longer operative time(513.17 ± 56.13 min vs 371.67 ± 85.53 min,P < 0.001).The TLPD group had significantly fewer mean numbers of days until bowel sounds returned(2.03 ± 0.55 d vs 3.83 ± 0.59 d,P < 0.001) and exhaustion(4.17 ± 0.75 d vs 5.37 ± 0.81 d,P < 0.001).The mean visual analogue score on postoperative day 4 was less in the TLPD group(3.5 ± 9.7 vs 4.47 ± 1.11,P < 0.05).No differences in surgery-related morbidities and mortality were observed between the two groups.Patients in the TLPD group recovered more quickly and required a shorter hospital stay after surgery(9.97 ± 3.74 d vs 11.87 ± 4.72 d,P < 0.05).A significant difference in the total cost was found between the two groups(TLPD 81317.43 ± 2027.60 RMB vs laparotomy 78433.23 ± 5788.12 RMB,P < 0.05).TLPD had a statistically higher cost for both surgery(24732.13 ± 929.28 RMB vs 19317.53 ± 795.94 RMB,P < 0.001)and anesthesia(6192.37 ± 272.77 RMB vs 5184.10 ± 146.93 RMB,P < 0.001),but a reduced cost for admission examination(50392.93 ± 1761.22 RMB vs 53931.60 ± 5556.94 RMB,P < 0.05).CONCLUSION:TLPD is safe when performed by experienced pancreatobiliary surgeons during the initial learning curve,but has a higher cost than open pancreaticoduodenectomy.

Utility of PET/CT in diagnosis, staging, assessment of resectability and metabolic response of pancreatic cancer

Pancreatic cancer is one of the most common gastrointestinal tumors, with its incidence staying at a high level in both the United States and China. However, the overall 5-year survival rate of pancreatic cancer is still extremely low. Surgery remains the only potential chance for long-term survival. Early diagnosis and precise staging are crucial to make proper clinical decision for surgery candidates. Despite advances in diagnostictechnology such as computed tomography(CT)and endoscopic ultrasound,diagnosis,staging and monitoring of the metabolic response remain a challenge for this devastating disease.Positron emission tomography/CT(PET/CT),a relatively novel modality,combines metabolic detection with anatomic information.It has been widely used in oncology and achieves good results in breast cancer,lung cancer and lymphoma.Its utilization in pancreatic cancer has also been widely accepted.However,the value of PET/CT in pancreatic disease is still controversial.Will PET/CT change the treatment strategy for potential surgery candidates?What kind of patients benefits most from this exam?In this review,we focus on the utility of PET/CT in diagnosis,staging,and assessment of resectability of pancreatic cancer.In addition,its ability to monitor metabolic response and recurrence after treatment will be emphasis of discussion.We hope to provide answers to the questions above,which clinicians care most about.

Risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy

BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1. serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level.1.68.tmol/L were the risk factors of PPFH. CONCLUSIONS; The risk of PPFH was found to be increased with high potential malignancy and high grade of POPE Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.

Meta-analysis of subtotal stomach-preserving pancreaticoduodenectomy vs pylorus preserving pancreaticoduodenectomy

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy(PPPD) and subtotal stomach-preserving pancreaticoduodenectomy(SSPPD).METHODS: Major databases including Pub Med(Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials(CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying(DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios(OR) or weighted mean difference(WMD) with 95% confidence intervals(95%CI) were calculated using either a fixed-effects or random-effects model. RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE(OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation(OR = 2.68; 95%CI: 0.77-4.58,P < 0.00001), with a tendency towards shorter time to liquid(WMD = 2.97, 95%CI:-0.46-7.83; P = 0.09) and solid diets(WMD = 3.69, 95%CI:-0.46-7.83; P = 0.08) as well as shorter inpatient stay(WMD = 3.92, 95%CI:-0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD =-217.70, 95%CI:-429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time(WMD =-5.30, 95%CI:-43.44-32.84; P = 0.79), pancreatic fistula(OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage(OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess(OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection(OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube(OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality(OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.

Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability

AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group.RESULTS CA125 > 38 U/mL(OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus(OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL(OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years(OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with postoperatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels(7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone(7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula(P = 0.072) or other complications(P = 0.230) and no greater impacts on length of hospital stay(P = 0.602) or post-operative diabetic control(P = 0.479).CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.

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

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

microRNA-218 suppresses the proliferation, invasion and promotes apoptosis of pancreatic cancer cells by targeting HMGB1

Objective： To detect the expression profiles of micro RNA-218（mi R-218） in human pancreatic cancer tissue（PCT） and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of mi R-218 on the expression of the target gene high mobility group box 1（HMGB1）, with an attempt to provide new treatment methods and strategies for pancreatic cancer.Methods： The expressions of mi R-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including As PC-1, Bx PC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction（q RT-PCR）. The change of mi R-218 expression in PANC-1 cells was detected using qR T-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8（CCK-8） was applied for detecting the effect of mi R-218 on the activity of PANC-1 cells. The effects of mi R-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of mi R-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of mi R-218 by luciferase reporter assay, and the effect of mi R-218 on the expression of HMGB1 protein in cells were determined using Western blotting.Results： As shown by q RT-PCR, the expressions of mi R-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue（NPT）（P〈0.01）. Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of mi R-218 mimic for 48 h（P〈0.01）. Growth curve showed that the cell viability significantly dropped after the overexpression of mi R-218 in the PANC-1 cells for two days（P〈0.05）. Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of mi R-218（P〈0.01） and the percentage of apoptotic cells significantly increased（P〈0.01）. As shown by the Trans-well migration assay, the enhanced mi R-218 expression was associated with a significantly lower number of cells that passed through a Transwell chamber（P〈0.01）. Luciferase reporter assay showed that, compared with the control group, the relative luciferase activity significantly decreased in the mi R-218 mimic group（P〈0.01）. As shown by the Western blotting, compared with the control group, the HMGB1 protein expression significantly decreased in the PANC-1 group after the transfection of mi R-218 mimic for 48 h（P〈0.01）.Conclusions： The mi R-218 expression decreases in human PCT and cell lines. mi R-218 can negatively regulate the HMGB1 protein expression and inhibit the proliferation and invasion of pancreatic cancer cells. A treatment strategy by enhancing the mi R-218 expression may benefit the patients with pancreatic cancer.

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 arterialreconstruction 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.

Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer

AIM:To determine the expression of toll-like receptor 9(TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216(CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance.METHODS:The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues,and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1.To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells,in vitro cell adhesion,wound-healing scrape,and invasion and cell colony formation were evaluated.RESULTS:TLR9 was highly expressed in pancreaticcancer tissues and PANC-1 cells.The percentage of positive cells expressing TLR9 protein in human pancreatic tissues,paracancerous tissues and normal tissues were 73.3%,33.3% and 20.0%,respectively,and the protein expression level of TLR9 was gradually descending(P < 0.05).In vitro tests in wound-healing scrape,cell adhesion,colony formation and matrigel invasion showed that the adhesion and motility of PANC-1 cells in CPG ODN 2216 treatment group were signif icantly lower than in the control group(P < 0.05).The cell growth assay showed that the proliferative ability of PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner(P < 0.05).CONCLUSION:The gene of TLR9 is correlated with the invasive and metastatic potential of human pancreatic carcinoma,and CPG ODN2216 induces the inhibition of migration and invasion of Panc-1 cells.

Diffusion-weighted imaging of pancreatic cancer

Magnetic resonance imaging(MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma(PDAC). Diffusion-weighted imaging(DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues(the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion(IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation(perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.

Recurrence and survival after surgery for pancreatic cancer with or without acute pancreatitis

BACKGROUND In pancreatic cancer,acute pancreatitis(AP)is a serious morbidity,but its negative effect on long-term outcomes remains to be elucidated.AIM To investigate the effects of AP on the tumor recurrence pattern of pancreatic ductal adenocarcinoma(PDAC)and tumor-specific survival.METHODS The medical records of 219 patients with curative pancreatectomy for pancreatic cancer at the Pancreatic Surgery Center of West China Hospital from July 2012 to December 2016 were analyzed retrospectively.The severity of acute pancreatitis was classified according to the Atlanta classification of AP.The patient demographics and tumor characteristics were assessed.Early recurrence was defined as a relapse within 12 mo after surgery.Overall and disease-free survival and recurrence patterns were analyzed.Mild acute pancreatitis was excluded because its negative effects can be negligible.RESULTS Early recurrence in AP group was significantly higher than in non-AP group(71.4%vs 41.2%;P=0.009).Multivariate analysis of postoperative early recurrence showed that moderate or severe AP was an independent risk factor for an early recurrence[odds ratio(OR):4.13;95%confidence interval(CI):1.41-12.10;P=0.01].The median time to recurrence was shorter in patients with AP than in those without(8.4 vs 12.8 mo;P=0.003).Multivariate analysis identified AP as an independent prognostic factor for overall survival[relative risk(RR):2.35;95%CI:1.45-3.83]and disease-free survival(RR:2.24;95%CI:1.31-3.85)in patients with PDAC.CONCLUSION Patients with moderate or severe acute pancreatitis developed recurrences earlier than those without.Moderate or severe AP is associated with shorter overall and disease-free survival of patients with PDAC.

Time to think: Selecting patients who may benefit from synchronous resection of primary pancreatic cancer and liver metastases

Pancreatic cancer remains a lethal disease and is associated with poor prognosis, particularly for patients with distant metastasis at diagnosis. Recently, Oweira reported a retrospective study that included 13233 metastatic pancreatic cancer patients from the Surveillance, Epidemiology and End Results database. They demonstrated that pancreatic cancer patients with isolated liver metastases had worse outcomes than patients with isolated lung metastases or distant nodal metastases. At present, the standard treatment for metastatic pancreatic cancer is chemotherapy. However, improvement in the safety of pancreatic surgery has led to the consideration of more aggressive surgical approaches. Schneitler reported two cases of hepatic metastatic pancreatic cancer in which negative margin(R0) resection and long survival were achieved after effective preoperative chemotherapy. In general, these two studies indicate that although pancreatic cancer patients with liver metastasis have a poor prognosis, surgical approaches may prolong survival for a few of these patients. A strategy to select hepatic metastatic pancreatic cancer patients who may benefit from surgical intervention is urgently needed.

Correlation between Protein Expression of PTEN in Human Pancreatic Cancer and the Proliferation,Infiltration,Metastasis and Prognosis

Summary： In order to investigate the correlation between protein expression of PTEN and the proliferation, infiltration, metastasis and prognosis in pancreatic cancer, immunohistochemical SP method was used to examine the protein expression of PTEN, PCNA, MVD, MMP-2, MMP-9 and TUNEL method to detect the levels of apoptosis of pancreatic cells in 41 pancreatic head cancers from regional pancreatectomy （RP） and 10 normal pancreatic tissues. The results showed that among 41 cases of pancreatic cancers, the positive staining of PTNE （39.02 %） was significantly weaker than that in normal pancreatic tissues （P〈0.05）. The levels of PCNA labeling index （LI）, apoptotic index （AI）, microvessel density （MVD）, MMP-2 LI and MMP-9 LI were decreased gradually with the increase of the expression intensity of PTEN, and there was a significant difference in the above parameters among the patients having different expression levels of PTEN （P〈0.01 or P〈0.05）. There was a negative correlation between the expression of PTEN and PCNA LI, MVD, MMP-2 LI, MMP-9 LI, and a positive correlation between AI and the expression of PTEN. The expression intensity of PTEN was correlated with the postoperative survival of the patients with pancreatic cancer （x^2=22.3400, P〈0.0001, RR=2.030）. It was suggested that the expression levels of PTEN protein were closely related with proliferation, infiltration and metastasis in human pancreatic cancer, and the expression of PTEN protein was one of the prognostic factors for pancreatic cancer following RP.