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Purpose: To investigate whether multiparametric quantitative diffusion weighted magnetic resonance imaging (DWI) can effectively predict the neoadjuvant therapy (NAT) response in borderline resectable pancreatic ductal adenocarcinoma (BRPC)., Methods: The clinicopathological data, including tumor size, location, and CA19-9 values, as well as DWI parameters(ADC, D, and f values) from 72 patients with BRPC, were analyzed. The differences and changes in these factors before and after NAT were compared to identify those most accurately reflect the response to NAT. ROC analysis was used to evaluate the diagnostic efficacy, and Kaplan-Meier survival analysis explored the relationship between DWI parameters and prognosis. Subgroup survival analysis to further identify populations potentially benefiting from NAT based on multiparametric DWI., Results: After-NAT, the response group showed significantly higher ADC and D values and lower f values compared to the non-response group. The ΔADC (OR: 12.24, P = 0.013) emerged as the most important independent factor for tumor response, demonstrating the highest diagnostic accuracy for NAT response with an AUC of 0.936. Kaplan-Meier showed the high ADC value group, high D value group and low f value group were associated with better prognosis after NAT; and the ΔADC ≥ 0 group, ΔD ≥ 0 group, and Δf < 0 group was significantly associated with better prognosis. In addition, subgroup analysis suggested two groups of patients might potentially benefit from NAT., Conclusions: Multiparametric quantitative DWI may offer valuable insights into the efficacy and prognosis of NAT in BRPC. These findings have the potential to support the evaluation and decision-making process for patients undergoing NAT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

Background: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30., Methods: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias., Results: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD., Conclusions: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD., (© 2023. The Author(s).)

Introduction: Postoperative pancreatic fistula (POPF) remains one of the main complications following pancreatic resection. Despite pancreatic fistula having a low postoperative mortality rate, the readmission and intervention rates in patients with pancreatic fistula are still considerable. Although there are several studies on pancreatic fistula development after pancreaticoduodenectomy, there are only a few studies on the feeding protocols applied after distal pancreatectomy or enucleation of pancreatic tumours. We designed this trial to test the hypothesis that early feeding does not increase the incidence of POPF and positively influences the long-term prognosis in patients who undergo distal pancreatectomy or enucleation of pancreatic tumours., Methods and Analysis: This is a prospective randomised controlled trial that will be conducted in a single centre. A total of 106 patients undergoing distal pancreatectomy or enucleation of pancreatic tumours will be recruited after providing informed consent. They will be randomly assigned to either an early or late feeding group. The early feeding group will begin enteral nutrition on postoperative day (POD) 3, and the late feeding group will begin enteral nutrition on POD7. The primary outcome is the incidence of POPF. The secondary outcomes include the length of postoperative hospital stay, postoperative complications, and indicators of long-term prognosis., Ethics and Dissemination: Peking University Third Hospital Medical Science Research Ethics Committee approved the study (M2021395). Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice., Trial Registration Number: ChiCTR2100053978., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The preoperative prediction of lymph node metastasis (LNM) in pancreatic ductal adenocarcinoma (PDAC) is essential in prognosis and treatment strategy formulation., Purpose: To compare the performance of computed tomography (CT) and magnetic resonance imaging (MRI) radiomics models for the preoperative prediction of LNM in PDAC., Material and Methods: In total, 160 consecutive patients with PDAC were retrospectively included, who were divided into the training and validation sets (ratio of 8:2). Two radiologists evaluated LNM basing on morphological abnormalities. Radiomics features were extracted from T2-weighted imaging, T1-weighted imaging, and multiphase contrast enhanced MRI and multiphase CT, respectively. Overall, 1184 radiomics features were extracted from each volume of interest drawn. Only features with an intraclass correlation coefficient ≥0.75 were included. Three sequential feature selection steps-variance threshold, variance thresholding and least absolute shrinkage selection operator-were repeated 20 times with fivefold cross-validation in the training set. Two radiomics models based on multiphase CT and multiparametric MRI were built with the five most frequent features. Model performance was evaluated using the area under the curve (AUC) values., Results: Multiparametric MRI radiomics model achieved improved AUCs (0.791 and 0.786 in the training and validation sets, respectively) than that of the CT radiomics model (0.672 and 0.655 in the training and validation sets, respectively) and of the radiologists' assessment (0.600-0.613 and 0.560-0.587 in the training and validation sets, respectively)., Conclusion: Multiparametric MRI radiomics model may serve as a potential tool for preoperatively evaluating LNM in PDAC and had superior predictive performance to multiphase CT-based model and radiologists' assessment.

Background & Aims: Tumor-initiating cells (TICs) drive pancreatic cancer tumorigenesis, therapeutic resistance, and metastasis. However, TICs are highly plastic and heterogenous, which impede the robust identification and targeted therapy of such a population. The aim of this study is to identify the surface marker and therapeutic target for pancreatic TICs., Methods: We isolated voltage-gated calcium channel α2δ1 subunit (isoform 5)-positive subpopulation from pancreatic cancer cell lines and freshly resected primary tissues by fluorescence-activated cell sorting and evaluated their TIC properties by spheroid formation and tumorigenic assays. Coimmunoprecipitation was used to identify the direct substrate of CaMKⅡδ., Results: We demonstrate that the voltage-gated calcium channel α2δ1 subunit (isoform 5) marks a subpopulation of pancreatic TICs with the highest TIC frequency among the known pancreatic TIC markers tested. Furthermore, α2δ1 is functionally sufficient and indispensable to promote TIC properties by mediating Ca 2+ influx, which activates CaMKⅡδ to directly phosphorylate PKM2 at T454 that results in subsequent phosphorylation at Y105 to translocate into nucleus, enhancing the stem-like properties. Interestingly, blocking α2δ1 with its specific antibody has remarkably therapeutic effects on pancreatic cancer xenografts by reducing TICs., Conclusions: α2δ1 promotes pancreatic TIC properties through sequential phosphorylation of PKM2 mediated by CaMKⅡδ, and targeting α2δ1 provides a therapeutic strategy against TICs for pancreatic cancer., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases., Methods: pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors., Results: From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade., Conclusions: The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Abuduhaibaier Sadula et al.)

Background: Pancreatic cancer (PC) is a highly aggressive and refractory disease, with disappointing 5-year survival rates. Regarding the wide application of neoadjuvant treatment in patients with PC, how the post-neoadjuvant Carbohydrate antigen 19-9 (CA19-9) response could translate into a survival benefit is not clearly understood. We aimed to evaluate the correlation of the CA19-9 response with overall survival (OS) in patients with PC receiving neoadjuvant therapy., Methods: An extensive electronic search in PubMed, Embase, and the Cochrane Library was performed to identify relevant articles, from which data relevant to independent correlations of the CA19-9 response with overall survival (OS) were extracted for analysis. A random-effects model was used to calculate the pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs)., Results: Altogether, 17 eligible studies were identified in the systematic review. Pooled analysis showed that CA19-9 response > 50% (HR, 0.43; 95% CI 0.29-0.56; P < 0.001) and normalization of CA19-9 (HR, 0.52; 95% CI 0.42-0.63; P < 0.001) after neoadjuvant treatment are significantly associated with promising overall survival. The results also showed that optimal CA19-9 response after neoadjuvant treatment was significantly related to a favorable prognosis (HR = 0.49, 95% CI 0.42-0.55, P < 0.001; I2 = 45.1%, P = 0.04). Subgroup analysis revealed there were no prognostic difference between CA19-9 > 50% and normalization of CA19-9 after neoadjuvant treatment (P = 0.338), but the duration of neoadjuvant chemotherapy over 4 months was significantly associated with expanded postoperative survival (P = 0.013)., Conclusions: Serum CA19‑9 is valuable in determining the effect of neoadjuvant treatment in patients with PC. Post-neoadjuvant CA19-9 response > 50% or CA19-9 normalization was related to a more promising overall survival, suggesting that optimal CA19-9 response may be a suitable prognostic index to guide treatment decisions.

Background: Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs., Methods: SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821., Findings: Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3-19·4) in the surufatinib group and 11·1 months (5·7-35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5-13·8) for surufatinib versus 3·7 months (2·8-5·6) for placebo (hazard ratio 0·49, 95% CI 0·32-0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression., Interpretation: Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population., Funding: Hutchison MediPharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs., Methods: SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing., Findings: Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1-16·7) in the surufatinib group and 16·6 months (9·2-not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4-11·1) in the surufatinib group versus 3·8 months (3·7-5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22-0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure)., Interpretation: Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population., Funding: Hutchison MediPharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Neuroendocrine tumor(NET) is a kind of highly heterogeneous and ubiquitous tumor, frequently localized in the gastrointestinal tract and pancreas. Surgery combined with regional ablation, endocrine therapy,chemotherapy and targeted therapy presents a favorable prognosis when treated with G1 or G2 gastroenteropancreatic neuroendocrine tumor(GEP-NET). However, there are only limited therapeutic strategies for metastatic unresectable tumors and poorly differentiated NEC,which are closely related to the special tumor microenvironment of neuroendocrine tumors.Targeting tumor microenvironment therapy is an important method in current systematic therapy, but till now the knowledge of neuroendocrine tumor microenvironment and its related treatment are limited. This article will specifically introduce the characteristics of tumor microenvironment in GEP-NET from the following aspects: the formation of enrichment vascular supply in TME,the role of tumor stroma,immune cells and cancer associacted fibroblast, and immune checkpoint and future trend of immunotherapy.

Introduction: Pancreatic cancer (PC) is one of the most aggressive malignancies, and it's difficult to diagnosis PC at an early stage, which leads to the poor prognosis of PC., Objectives: To identifiy the possible prognosis or dignosis metabolite biomarkers in the serum exosome of PC patients., Methods: We employed LC-DDA-MS based untargeted lipidomic analysis to search for potential candidate biomarkers in the serum exosome of PC patients. Then LC-MRM-MS based targeted lipid quantification was used to validate the trends of the candidate biomarkers in larger sample cohorts., Results: About 270 lipids belonging to 20 lipid species were found significantly dysregulated between the serum exosome of PC patients and healthy controls. 61 of them were validated in larger samples size. We further analysis the correlation between these dysregulated lipids and other PC related factors, and results show that LysoPC 22:0, PC (P-14:0/22:2) and PE (16:0/18:1) are all associated with tumor stage, CA19-9, CA242 and tumor diameter. What's more, PE (16:0/18:1) is also found to be significantly correlated with the patient's overall survival., Conclusion: These data reveal dysregulated lipids in serum exosome of PC patients, which have potential to be biomarkers for diagnosis, or unveil pathological relationship between exosome and PC progress.

Background: There were many reports suggesting that different kinds of tumors can express B7-H4; however, the prognostic value in cancer was still unclearly. Therefore, we conducted a meta-analysis to investigate the relationship between overexpression of B7-H4 with the prognostic value in pancreatic cancer patients., Materials and Methods: The Pubmed, Embase, Cochrane Library, Ovid, Web of Science, and Chinese research database (including CBM, CNKI, and WAN FANG) were searched for related literature published until October 12, 2017. The pooled odds ratios (ORs) and/or pooled hazard ratios (HRs) for clinical pathological factors and overall survival (OS) were calculated and analyzed using Stata software. To assess whether an individual study had an impact on the result, sensitivity analysis was performed for all included individual studies using the fixed-effects model. Publication bias was evaluated using Egger's and Begg's tests., Results: Data from 6 observational studies including 442 patients were summarized in this meta-analysis, and each study was eligible for inclusion based on included and exclude criteria. The pooled results indicated that the B7-H4 overexpression could predict the presentation of lymph node metastasis (OR = 3.94, 95% CI: 1.22-12.66, P = .022), advanced TNM stage (T = the extent of the primary tumor, N = regional lymph nodes, M = distant metastases) (III+IV vs I+II; OR = 7.63, 95% CI: 2.46-23.66, P < .001), and the poor OS (HR = 3.00, 95%CI = 2.20-4.10, P < .001) in PC patients., Conclusions: This study reveals that high expression of B7-H4 is an unfavorable prognostic factor for patients with pancreatic cancer. These results may guide the clinical management of this patient population.

Background: Platelet to lymphocyte ratio (PLR) was recently reported being associated with the prognosis of pancreatic cancer (PC), but the prognostic value of PLR in pancreatic cancer remains inconsistent. We conduct a meta-analysis to evaluate the prognostic role of PLR in patients with PC., Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for eligible studies which investigated the relationship between PLR and clinical outcome of patients with pancreatic cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic role of PLR in overall survival (OS) and progression-free survival (PFS)/time to progression (TTP)., Results: A total of 16 studies comprising 3028 patients with PC were enrolled in this meta-analysis. Pooled analysis demonstrated that elevated PLR predicted a poor OS (HR = 1.22, 95% CI: 1.09-1.36, P < .001). Prognostic role of PLR on OS were significant in subgroup of Asians (HR = 1.22, 95% CI: 1.11-1.34, P < .001), patients treated with chemotherapy (HR = 1.18, 95% CI: 1.04-1.35, P = .01) and mixed methods (HR = 1.29, 95% CI: 1.07-1.57, P = .009), American joint committee on cancer (AJCC) stage of III-IV (HR = 1.22, 95% CI: 1.09-1.36, P < .001), pathological subtype of pancreatic adenocarcinoma (HR = 1.21, 95% CI: 1.08-1.36, P = .001), and cut-off value of PLR ≥160 (HR = 1.48, 95% CI: 1.25-1.75, P < .001)., Conclusions: An elevated PLR is associated with unfavorable overall survival in patients with pancreatic cancer.

Liver metastasis is the one of the main prognostic factors of pancreatic neuroendocrine neoplasm (PNEN). With the development of multidisciplinary collaboration among surgical oncology, medical oncology, and intervention treatment, the treatment of PNEN with liver metastasis gradually tends to become diversification. Surgery is still the only way for curing the patients with pancreatic neuroendocrine tumor with liver metastasis when the histological types are G1 and G2. Medical oncology and intervention treatment could be selected for those having PNEN with diffuse liver metastasis or those cannot tolerate surgery. Liver transplantation only suits for a small number of selected patients. The present article explored the relationship between histological classifications and the treatment options of PNEN with liver metastasis, and discussed the specific treatments from perspectives of surgical treatment, medical treatment and intervention treatment.

As a poor prognosis indicator in patients with pancreatic ductal adenocarcinoma (PDCA), lymph node (LN) metastasis is of great importance in treatment. Present study was performed to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and possible clinical parameters on the LN metastasis in PDCA patients. A total of 159 operable patients with PDCA were enrolled in our study. The clinical utility of NLR and other clinical parameters was evaluated by receiver operating characteristic (ROC) curves. Overall survival analysis indicated that LN metastasis is an independent prognostic factor. The logistic analysis was used to determine the independent parameters associated with LN metastasis. Ideal cutoff values for predicting LN metastasis are 2.12 for NLR and 130.96 for PLR according to the ROC curve. Multivariate analyses indicate that NLR (HR 2.588; 95% CI 1.246-5.376; P = 0.011), CA125 (HR 6.348; 95% CI 2.056-19.594; P = 0.001) and CA19-9 (HR 2.738; 95% CI 1.151-6.515; P = 0.023) are associated significantly with LN metastasis independently. Preoperative NLR, CA125 and CA19-9 are useful biomarkers for the prediction of LN metastasis in PDCA patients.

During our research on circulating tumor cells (CTCs) derived from tumor-adjacent vessels in pancreatic ductal adenocarcinoma (PDAC), we found that CTCs are sometimes surrounded by white blood cells (WBCs) in blood. We hypothesize that such interaction between WBCs and CTCs in blood is a mechanism by which WBCs assist in the metastasis of CTCs. We present our laboratory finding, with our evaluation of the association between the neutrophil-to-lymphocyte ratio (NLR, the most investigated clinical parameter of WBCs) and distant metastasis after curative surgery in PDAC. The laboratory finding was presented through immunofluorescence. In the clinical segment, we performed a retrospective study on PDAC patients with distant metastasis after curative surgery who were referred to Peking University Third Hospital between 2005 and 2014. The data on the possible clinical factors were collected by a retrospective review of the patients' records. Immunofluorescence results showed that CTCs are surrounded by WBCs in tumor-adjacent vessels of PDAC patients. In the clinical segment, 112 (70%) of a total of 160 PDAC patients were found to have developed distant metastases after surgery; among the 112 patients, only 89 had entire data and were enrolled for further analysis (84.3% patients had liver metastasis). No significant association was found between the NLR and overall survival (hazard ratio [HR] = 1.027, 95% confidence interval [CI] 0.723-1.459, P = 0.88); however, a significant relationship between the NLR and distant metastasis after curative surgery was found on the univariate (HR = 1.641, 95% CI 1.058-2.545, P = 0.027) and multivariate analyses (HR = 2.15, 95% CI 1.279-3.615, P = 0.004). Neutrophils might assist in distant metastasis through interaction with CTCs in blood. Moreover, NLR is an effective predictor for distant metastasis after curative surgery for PDAC., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To explore the value of Roux-en-Y pancreaticojejunostomy after local pancreatic head resection in treating benign tumors of pancreatic head (BTPH)., Methods: The clinical data of 12 patients diagnosed as BTPH and treated by Roux-en-Y pancreaticojejunostomy after local pancreatic head resection in Department of General Surgery, Peking University Third Hospital from November 2006 to October 2013 were retrospectively analyzed.Of the 12 cases, 5 patients were male, 7 patients were female, the age of patients ranged from 21 to 64 years(average 42.3 years). Diameter of tumors was 3.0-4.8 cm.Diameter of pancreatic wound after resection was 5.1-7.9 cm, and main pancreatic duct injury happened in 1 case., Results: Two cases of mucinous cystadenoma, 2 insulinoma, 3 solid pseudopapillary tumor and 4 nonfunctional pancreatic neuroendocrine tumors were confirmed histopathologically.No mortality and pancreatic leakage occurred during the perioperative period.All the 12 patients had no sign of recurrence.Experienced good life quality without occurrence of diabetes during the follow-up period of 24-108 months(more than 60 months in 4 cases)., Conclusions: Roux-en-Y pancreaticojejunostomy after local pancreatic head resection is a reasonable choice for benign tumors of the pancreatic head as long as the patient is properly selected.

Background: Alpha-fetoprotein (AFP)-producing pancreatic neuroendocrine tumors (pNETs) are rare, and the few reported cases usually coexisted with other malignant components such as adenocarcinoma or hepatoid carcinoma. We present here the first case of pure AFP-producing pNET., Case Presentation: A 56-year-old male patient underwent resection of the pancreatic tail and body because of elevated serum AFP levels and pancreatic mass. Microscopy showed that the tumor tissue consisted of large and small solid nests of polygonal cells. The tumor cells were positive for chromogranin A, synaptophysin, CD99, cytokeratin 19, pan-cytokeratin and β-catenin, and also showed diffuse immunoreactivity for AFP and human chorionic gonadotrophin. The mitotic rate was nearly 30 per 10 high-power fields and the Ki-67 index was nearly 25%. The histopathologic findings supported the diagnosis of an AFP-producing pNET. Other malignant components were not found. Serum AFP levels decreased to near-normal after operation and gradually increased to >1000 ng/ml at 5 months post-surgery. Recurrence and hepatic metastases were revealed by computed tomography. The patient died 21 months after surgery., Conclusion: This was the first case of pure AFP-producing pNET to be reported in the English literature. Serum AFP levels may provide useful information for monitoring the therapeutic effectiveness, early recurrence or metastases.

Objective: To analyze the R1 rate of the pancreatic head carcinoma resection specimens which delt with a unified protocol by two different R1 criteria., Methods: Between November 2011 and October 2013, a unified pathological protocol was prospectively used to handle 70 consecutive pancreatioduodenectomy specimens for pancreatic ductal adenocarcinoma. Apart from the pancreatic transection margin, the bile duct and stomach/jejunum margins, different colors were used to stain the anterior surface, the superior mesenteric vein (SMV) groove margin, the superior mesenteric artery (SMA) margin, and the posterior surface. Axial slicing technique was used to dissect the pancreatioduodenectomy specimens., Results: Among the 70 patients, 3, 30 and 37 patients were classified as well, moderately and poorly differentiated respectively;7, 15 and 48 patients were classified as pT1, pT2 and pT3 respectively.Forty patients (57.1%) had metastases in regional lymph nodes (pN1) , and 16 patients (22.9%) had metastases in para-aortic nodes.Resection of the portal vein and/or the superior mesenteric vein was performed in 13 patients (18.6%) .When applying the UICC criteria, 26 cancer resections were classified R1 (37.1%) , 33 margins were turned out to be R1. The SMV groove margin and SMA margin were infiltrated in 13 specimens (13/33, 39.4%) respectively.When applying the Royal College of Pathologist's criteria, 39 cancer resections were classified R1 (55.7%) , 51 margins were turned out to be R1. The SMV groove margin and SMA margin were infiltrated in 18 (18/51, 35.3%) and 19 (19/51, 37.3%) specimen respectively.Until April 2014, the median follow-up was 18(range 6-42) months., Conclusions: Applying the unified protocol for pancreatic head ductal adenocarcinoma specimens results in an significant R1 rate of the resection margins, and the R1 rate is related to the R1 criterion. The SMV groove margin and SMA margin are the two most frequent sites of R1.

Aims: It has been reported that glucagon-like peptide-1 (GLP-1) agents are associated with an increased risk of pancreatic cancer in patients with type 2 diabetes. Reports have indicated that GLP-1 promotes pancreatic metaplasia and premalignant lesions. The aims of this study were to determine the effects of GLP-1-based therapy on pancreatic cancer cells., Methods: Immunohistochemistry was used to investigate GLP-1 receptor (GLP-1R) expression in 30 human pancreatic cancer tissues. We also analysed associated clinicopathological data and each patient's prognosis. Two human pancreatic cancer cell lines were used to evaluate the in vitro effects of the GLP-1R agonist liraglutide on cell growth, migration and invasion. Mouse xenograft models of human pancreatic cancer were established to evaluate the effects of liraglutide in vivo., Results: Human pancreatic cancer tissues showed lower levels or a lack of GLP-1R expression when compared with levels in the tumour-adjacent pancreatic tissues. Negative GLP-1R expression occurred more frequently in advanced tumours with larger diameters and lymphatic metastasis, and was associated with a poor prognosis. GLP-1R activation with liraglutide inhibited tumourigenicity and metastasis of human pancreatic cancer cells in vitro and in vivo. Akt activation was dose-dependently inhibited by liraglutide, and the PI3K inhibitors, LY294002 and wortmannin, displayed similar suppressive effects to liraglutide in human pancreatic cancer cells., Conclusions: GLP-1R activation has an antitumour effect on human pancreatic cancers via inhibition of the PI3K/Akt pathway. This finding suggests that GLP-1-based therapies may be beneficial, rather than harmful, in treating type 2 diabetic patients with pancreatic cancer., (© 2014 John Wiley & Sons Ltd.)

Background: Pancreatic neuroendocrine tumors (pNETs) are a type of tumors with the characteristics of easy metastasis and recurrence. Till date, the risk factors affecting the prognosis are still in the debate. In this study, several risk factors will be discussed combined with our cases and experience., Methods: Thirty-three patients diagnosed as pNETs were enrolled and the clinical features, blood tests, pathological features, surgical treatment, and follow-up data of these patients were collected and analyzed., Results: In this study, operation time of G3 cases was longer than G1/G2 cases (P = 0.017). The elevated level of tumor markers such as AFP, CEA, Ca125, and Ca19-9 may predict easier metastasis, earlier recurrence, and poor prognosis (P = 0.007). The presence of cancer embolus and nerve invasion increases along with the TNM stage (P = 0.037 and P = 0.040), and the incidence of positive surgical margin increased (P = 0.007). When the presence of nerve invasion occurs, the chance of cancer embolus and lymph node metastasis also increases (P = 0.016 and P = 0.026)., Conclusions: pNETs were tumors with the features of easy recurrence and metastasis and many risk factors could affect its prognosis such as the elevated levels of tumor markers and the presence of nerve invasion, except some recognized risk factors. If one or more of these factors existed, postoperative treatments may be needed to improve prognosis.

Background: Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic cystic neoplasm, accounting for 1% of all exocrine pancreatic neoplasms. This study aimed to summarize the clinicopathological and biological behaviors, as well as the experience in diagnosis and treatment of IPMN., Methods: Clinicopathological data were collected from 36 cases with IPMN who were treated in Department of General Surgery, Peking University Third Hospital from May 2001 to July 2011., Results: The 36 cases of IPMN patients included 27 males and 9 females (M:F = 3:1). The age of patients ranged from 52 to 78 years, with an average of 67.3 years. Regarding tumor location, 20 tumors were located in pancreatic head, 3 in pancreatic neck, 10 in pancreatic body and tail, and 3 in the whole pancreas. All the 36 cases underwent surgical treatment, with 13 cases of pancreaticoduodenectomy, 3 cases of middle pancreatectomy, 7 cases of tumor resection plus pancreaticojejunostomy, 3 cases of distal pancreatectomy, 7 cases of distal pancreatectomy plus spleen resection, and 3 cases of total pancreaticoduodenectomy. Of the 36 patients, 9 patients underwent the operations under laparoscopy. The 36 cases included main duct type (14 cases, 38.9%), branch duct type (10 cases, 27.7%), and mixed duct type (12 cases, 33.3%). Pathologically, of the 36 cases, there were 7 IPMN adenomas, 11 borderline IPMNs, 6 IPMN with carcinomas in situ, and 12 IPMNs with invasive carcinomas. All the 36 cases were followed up. During an average of 42 months follow-up period (26-129 months), no recurrence occurred., Conclusions: IPMN, which primarily occurs in male, is a low-grade malignancy which may involve any part of the pancreas, with specific clinicopathological features. IPMN is a different malignancy type from pancreatic ductal carcinoma. Imaging and laboratory examination are helpful for the diagnosis and differential diagnosis. The prediction of invasive IPMN is still difficult. Surgical resection is recommended as the first choice of treatment. Aggressive and proper operation procedure produces better prognosis. Long-term follow-up is necessary for patients after operation. Laparoscopic distal pancreatectomy is a feasible and safe procedure for the indicated patients.

Background: To assess the efficacy of intraoperative ultrasound-guided implantation of 125I seeds for the treatment of unresectable pancreatic carcinoma, and analyze the associated prognostic factors., Methods: Twenty-eight patients with pancreatic carcinoma who underwent laparotomy and were considered to have unresectable tumors were included in this study. Nine patients were pathologically diagnosed with Stage II disease, and nineteen patients with Stage III disease. Twenty-eight patients received intraoperative ultrasound-guided 125I seed implantation and received a D90 (at least 90% of the tumor volume received the reference dose) ranging from 60 to 163 Gy, with a median of 120 Gy. Seven patients received an additional 35-50 Gy external beam radiotherapy after seed implantation, and ten patients received two to ten cycles of chemotherapy. Overall survival of the patients was calculated and prognostic factors were evaluated., Results: Of the patients, 94.1% (16/17) achieved good to medium pain relief. The tumor response rate was 78.6% (22/28), and local control was achieved in 85.7% (24/28) of patients. The 1-, 2- and 3-year survival rates were 30%, 11% and 4%, and the median survival was 10.1 months (95% CI: 9.0-10.9). Analysis using the Cox proportional hazards model suggested that patients younger than 60 years and patients who received a D90 higher than 110 Gy may survive for a longer period., Conclusions: I seed implantation provides a safe and effective method to relieve pain, control local tumor growth and, to some extent, prolong the survival of patients with stage II and III pancreatic disease, without additional complications. Age and accumulated dose may be factors predictive of a favorable outcome for patients with unresectable pancreatic carcinoma treated with 125I seeds. These findings need to be validated by conducting further studies with larger cohorts.

Background: To assess the feasibility and efficacy of using 125I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma., Methods: Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with 125I seed implantation guided by intraoperative ultrasound and received D90 of 125I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35-50 Gy from external beam radiotherapy after seed implantation and six patients received 2-6 cycles of chemotherapy., Results: 87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7-12.3)., Conclusion: There were no deaths related to 125I seed implant. In this preliminary investigation, 125I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.