Search

Background Pancreatic ductal adenocarcinoma（PDAC）is the seventh leading cause of cancer-related death globally. It has an extremely poor prognosis, and its incidence rate and mortality are considered to increase sharply over the next few years. Combined chemotherapy after surgery is still the best treatment, and it is also the only curative option. Improvements in the understanding of genetic mutations, the tumor microenvironment (TME), and targeted therapies continue to improve the progression of PDAC. Nerves are an important component of the TME of pancreatic cancer. However, the role of cancer-nerve crosstalk-related genes in PDAC is still unclear. Results In our study, we constructed a prognostic model based on cancer-nerve crosstalk-related genes with prognostic value. The xCell algorithm was used to analyse the cell component enriched from samples in The Cancer Genome Atlas (TCGA) PDAC cohort. We found the neuronal content was significantly correlated with prognosis. Protein-protein interaction (PPI) network, GO, and KEGG enrichment analyses were used to identify nerve-related genes in PDAC. From the forty-two nerve-cancer crosstalk genes, we used K-M plotter to identify the canditate genes for LASSO regression. We constructed a three-gene prognostic model (CHRNB2, CHRNA10, NGFR). The model could effectively test and verify its 1-, 3- and 5-year survival rates in the TCGA-PDAC cohort. The effectiveness of the model was verified by external test data. The genes of this model were highly related to tumor progression and other immune microenvironments. Conclusion In summary, we used bioinformatics analysis to construct an effective prognostic model, explored the key mechanism of nerve-cancer cross-talk and revealed the potential of cancer-nerve cross-talk-related genes as prognostic biomarkers and therapeutic targets in PDAC.

To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p

Yong Gao,1,* Baobao Cai,1,* Lingdi Yin,1,* Guoxin Song,2 Zipeng Lu,1 Feng Guo,1 Jianmin Chen,1 Chunhua Xi,1 Jishu Wei,1 Junli Wu,1 Wentao Gao,1 Kuirong Jiang,1 Yi Miao1,3 1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Miao, Email miaoyi@njmu.edu.cnBackground: Undifferentiated carcinoma of pancreas with osteoclast-like giant cells is an extremely rare tumor in pancreas. It is relatively difficult to have preoperative diagnosis due to the lack of specific tumor markers and pre-operative images.Methods: In the present study, database of the pancreas center in the First Affiliated Hospital of Nanjing Medical University was retrospectively screened. A total of thirteen cases diagnosed as undifferentiated carcinoma of pancreas with osteoclast-like giant cells were included. Their clinical data and treatments were collected.Results: Thirteen patients include eight males and five females, and the median age was 67 (60– 72) years old. The lesions were found in more than half patients through health examination with no symptoms. NSE was elevated in eight cases (66%). CT scan revealed that cystic and solid lesions often had thick (4/5), contrast-enhanced (5/5) wall with smooth edges (5/5) and the boundary of lesions mainly with solid composition (4/10) is not well demarcated with normal pancreatic parenchyma. All patients received surgical resection. Eight patients had adjuvant chemotherapy and only one patient had adjuvant radiotherapy. The median survival time was 13 months. Five patients had postoperative metastasis or recurrence of tumor and four of them had died of this disease during follow-up.Conclusion: Our data showed that elevated level of NSE and characteristic pre-operative images might provide aid with the pre-operative diagnosis for undifferentiated carcinoma of pancreas with osteoclast-like giant cells. Patients with suspected diagnosis should receive surgical intervention as soon as possible, supplemented with postoperative chemotherapy, in order to prolong the survival of patients.Keywords: pancreatic cancer, undifferentiated carcinoma of pancreas, osteoclast-like giant cells, retrospective, pre-operative image

Pasireotide was recently suggested for the prevention of postoperative pancreatic fistula (POPF) after pancreatic surgery. However, its efficacy remains to be controversially dicussed. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of pasireotide for preventing POPF after pancreatic surgery. A systematic literature search was conducted in PubMed, Web of Science, and The Cochrane Library to identify clinical studies investigating the efficacy of pasireotide after pancreatic surgery. The identified studies were critically appraised, and meta-analyses were then performed. The study was performed in accordance with PRISMA guidelines and was registered at the PROSPERO study database (CRD42018112334). Four studies with a total of 919 patients were included: 418 with pasireotide treatment and 501 controls. Meta-analysis showed that pasireotide could reduce neither clinically relevant POPF rate (OR = 0.78; 95% CI, 0.49–1.24; P = 0.29) nor overall POPF rate (OR = 0.94; 95% CI, 0.60–1.48; P = 0.80) after pancreatic resections. There were no significant differences in delayed gastric emptying, mortality, and postoperative hospital stay after pancreatic surgery. However, pasireotide reduces readmission after pancreatic surgery (OR = 0.61; 95% CI, 0.44–0.85; P = 0.004). Subgroup analyses revealed that prophylactic use of pasireotide did not reduce the incidence of clinically relevant POPF after pancreaticoduodenectomy or distal pancreatectomy compared with the control. Based on the available evidence, use of pasireotide may not reduce clinically relevant POPF as well as it may not improve postoperative course substantially after pancreatic surgery. Further investigator-initiated high-quality trials are needed.

Multimodal sentiment analysis has been an active subfield in natural language processing. This makes multimodal sentiment tasks challenging due to the use of different sources for predicting a speaker’s sentiment. Previous research has focused on extracting single contextual information within a modality and trying different modality fusion stages to improve prediction accuracy. However, a factor that may lead to poor model performance is that this does not consider the variability between modalities. Furthermore, existing fusion methods tend to extract the representational information of individual modalities before fusion. This ignores the critical role of intermodal interaction information for model prediction. This paper proposes a multimodal sentiment analysis method based on cross-modal attention and gated cyclic hierarchical fusion network MGHF. MGHF is based on the idea of distribution matching, which enables modalities to obtain representational information with a synergistic effect on the overall sentiment orientation in the temporal interaction phase. After that, we designed a gated cyclic hierarchical fusion network that takes text-based acoustic representation, text-based visual representation, and text representation as inputs and eliminates redundant information through a gating mechanism to achieve effective multimodal representation interaction fusion. Our extensive experiments on two publicly available and popular multimodal datasets show that MGHF has significant advantages over previous complex and robust baselines.

Middle segment-preserving pancreatectomy (MPP) can treat multilocular diseases in the pancreatic head and tail while avoiding impairments caused by total pancreatectomy (TP). We conducted a systematic literature review of MPP cases and collected individual patient data (IPD). MPP patients (N = 29) were analyzed and compared to a group of TP patients (N = 14) in terms of clinical baseline characteristics, intraoperative course, and postoperative outcomes. We also conducted a limited survival analysis following MPP. Pancreatic functionality was better preserved following MPP than TP, as new-onset diabetes and exocrine insufficiency each occurred in 29% of MPP patients compared to near-ubiquitous prevalence among TP patients. Nevertheless, POPF Grade B occurred in 54% of MPP patients, a complication avoidable with TP. Longer pancreatic remnants were a prognostic indicator for shorter and less eventful hospital stays with fewer complications, whereas complications of endocrine functionality were associated with older patients. Long-term survival prospects after MPP appeared strong (median up to 110 months), but survival was lower in cases with recurring malignancies and metastases (median < 40 months). This study demonstrates MPP is a feasible treatment alternative to TP for selected cases because it can avoid pancreoprivic impairments, but at the risk of perioperative morbidity.

Simple Summary Pancreatic ductal adenocarcinoma is a devastating illness but guidelines consider it unresectable once metastasized. However, resection of the primary tumor is carried out in select cases and retrospective analyses indicate that this may improve survival. Even so, these analyses are limited to single centers or fail to account for biased patient selection. We overcome these limitations with a propensity score-matched SEER database analysis that reliably demonstrates surgery can extend overall survival. Furthermore, we identify prognostic factors that could aid the selection of patients for randomized controlled trials. Thus, this study paves the way for future work that aims to update treatment guidelines in accordance with surgical developments. Abstract Guidelines do not recommend resection surgery for oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, reports in small samples of selected patients suggest that surgery extends survival. Thus, this study aims to gather evidence for the benefits of cancer-directed surgery (CDS) by analyzing a national cohort and identifying prognostic factors that aid the selection of candidates for CDS or recruitment into experimental trials. Data for patients with PDAC and hepatic metastasis were extracted from the population-based Surveillance, Epidemiology, and End Results database (SEER). The bias between CDS and non-CDS groups was minimized with Propensity Score Matching (PSM), and the prognostic role of CDS was investigated by comparing Kaplan-Meier estimators and Cox proportional hazard models. A total of 12,018 patients were extracted from the database, including 259 patients who underwent CDS that were 1:1 propensity score-matched with patients who did not receive CDS. CDS appeared to significantly prolong median overall survival from 5 to 10 months. Multivariate analysis revealed chemotherapy as a protective prognostic, whilst survival was impaired by old age and tumors that were poorly differentiated (Grades III–IV). These factors can be used to select patients likely to benefit from CDS treatment, which may facilitate recruitment into randomized controlled trials.

Pancreatic anastomosis reconstruction is one of the most technically demanding and complicated procedures in general surgery. No single technique has been demonstrated to be superior to the others in the prevention of postoperative pancreatic fistula (POPF), and the accumulation of surgical experience is closely related to the quality of this anastomosis. The aim of the current study was to evaluate the feasibility of our simplified technique, single-layer continuous duct-to-mucosa pancreaticojejunostomy.A single-center prospective single-arm trial was performed. The first 20 patients who underwent Whipple's procedure with the new technique performed by a single surgeon in our center were recruited. General information, preoperative treatments, risk factors for POPF, and postoperative morbidity of the patients were prospectively recorded and reported.From January to February 2020, 13 male and 7 female patients were included. Ten cases were classified as intermediate/high risk according to validated fistula prediction models. The median operation time was 260 min, including a median pancreaticojejunostomy time of 7.7 min. There were 2 cases (10%) of grade B POPF, and no grade C POPF occurred. The overall morbidity rate was 30%, including 2 cases with severe complications (Clavien-Dindo grade ≥ 3). No patients underwent reoperation, and no patient died within 90 days after surgery. The median length of hospitalization was 11 days.Single-layer continuous duct-to-mucosa pancreaticojejunostomy is a simplified and feasible method for pancreatic anastomosis. Further studies are warranted to evaluate the indications or contraindications and efficacy of preventing POPF with our new technique.

Background: Idiopathic chronic calcific pancreatitis is a rare entity. Early surgical intervention and a parenchyma sparing procedure should be advocated to prevent further decay of the pancreas and the occurrence of cancer. Case Presentations: Case 1: A 14-year-old boy presented with a 3-year history of right upper abdominal pain that has been aggravated in the last 2 months. Imaging revealed a dilated pancreatic duct of 6 mm with pancreatic duct stones in the head of pancreas. He underwent a Frey's procedure. Unfortunately, he was discharged with grade B pancreatic fistula. Case 2: A 12-year-old boy presented with a 1-year history of dull and recurring epigastric pain. Imaging studies showed multiple stones in a 12 mm dilated pancreatic duct. The patient underwent a modified Puestow procedure. Up to the 42th month follow-up, the patient had no pain complaints. Case 3: A 12-year-old boy with a 1-week history of a dull epigastric pain presented with with multiple stones in a 10 mm duct. He underwent a modified Puestow procedure and was discharged with alleviated pain. Conclusions: “Conservative” surgery allows satisfactory pancreatic duct drainage, reduced rehospitalizations, and longer pain relief than alternative endoscopic procedures.

Pancreatic cancer (PC) has posed a great health threat to a growing number of people all over the world. Detection of serum miRNAs, being sensitive, noninvasive, and easy to obtain, has a great potential of being a novel screening method for PC patients. In this study, we investigated miRNA expression levels in serum by qRT‐PCR. The study was divided into four phases: the screening, training, testing, and external validation stage. We firstly chose candidate miRNAs using Exiqon panels in the screening phase. Then, a total of 129 PC serum samples and 107 normal controls (NCs) were further analyzed in the following training and testing phases to identify differently expressed miRNAs. A cohort of 30 PC serum samples vs 30 NCs was used to confirm the diagnostic value of the identified miRNAs in the external validation phase. Moreover, miRNA expressions in additional 44 PC tumor tissue samples and the matched adjacent normal tissue samples as well as 32 pairs of serum‐derived exosomes samples were also further explored. As a result, we identified six significantly upregulated miRNAs in the serum of PC: let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p. A six‐miRNA panel in serum was then established. The area under the receiver operating characteristic curves (AUC) for the panel was 0.910 for the combined training and testing phases, which showed higher diagnostic value than the individual miRNA. Prognostic value prediction using Cox's proportional hazards model and Kaplan‐Meier curves showed that increased serum miR‐19a‐3p was closely related to worse overall survival (OS). In addition, significant upregulation of miR‐192‐5p, miR‐19a‐3p, and miR‐19b‐3p was observed in both PC tissue and serum‐derived exosomes samples. In conclusion, we identified a six‐miRNA (let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p) panel in the serum for PC early and noninvasive diagnosis.

Central pancreatectomy (CP) has been applied for treating benign and low-grade malignant tumors in pancreatic neck, but studies regarding CP for pancreatic ductal adenocarcinoma (PDAC) are quite limited. We aimed to investigate the role of central pancreatectomy in the treatment of PDAC in the neck of the pancreas. Patients who underwent CP at our hospital between 2009 and 2016 were identified. Patients treated by distal pancreatectomy (DP) were matched according to the tumor size, location, and staging. The surgical and survival outcomes were compared between the CP and DP groups. Nine patients had CP. Five (56%) had postoperative complications and three (33%) had clinically significant (grade B + C) fistula. No significant difference was found between the CP and DP groups for the rate of overall morbidity, pancreatic fistula, reoperation, and readmission. Tumor size was smaller in the CP group compared to the DP group. The mortality of both groups was zero. The median postoperative survival was similar between the two groups (20.4 months for CP vs 19.4 months for DP, P = 0.842). CP is safe for patients with small PDAC at the neck of the pancreas. Considering the good preservation of pancreatic endocrine and exocrine functions, CP could be considered as an alternative procedure for single small PDAC in pancreatic neck.

HHLA2 is a newly identified member of the B7 immune checkpoint family, but its function and crosstalk with immune cells is not fully understood. To gain insights into the HHLA2 expression profile and to determine the clinical significance and function of HHLA2 in pancreatic cancer, we performed immunohistochemistry (IHC) analyses on tissue microarrays (TMAs) of pancreatic ductal adenocarcinoma (PDAC, n = 92) with matched peritumoral tissues as well as in cohorts of precancerous lesions: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). We found that HHLA2 was rarely detected in normal acinar, islet, and ductal cells but widely expressed from early pancreatic precancerous lesions to invasive PDAC. The overall HHLA2 positivity was 95% (19/20) in low grade PanIN and 70.73% (29/41) in IPMN. HHLA2 expression was detected in 77.17% (71/92) of the PDAC cases and was significantly associated with better prognosis in this cohort. Our findings suggest that HHLA2 may behave as a costimulatory ligand in pancreatic cancer, which differs from other B7 family members that are largely characterized as checkpoint inhibitors. Further investigation of the HHLA2 signaling pathway and its receptors is warranted by our data and may lead to novel therapeutic interventions.

To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated.In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery.From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively.The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

Background: Abdominal tuberculosis (TB) remains an issue as it masquerades as many malignant or benign abdominal conditions. Objective: To analyze the clinical and laboratory features of abdominal ...

This study is to analyze differentially expressed genes (DEGs) and mutation signatures of pancreatic head cancer and pancreatic body/tail cancer. Pancreatic Adenocarcinoma (PAAD) RNA-seq data, mutation data and clinical data were downloaded and collected from The Cancer Genome Atlas (TCGA), FireHose and CBioPortal. According to the anatomic location, the patients were divided into 146 cases of pancreatic head cancer and 28 cases of pancreatic body/tail cancer. Then survival analysis was performed by Kaplan–Meier and log-rank test. Furthermore, DEGs were screened by R package Deseq2. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) were then carried out by DAVID and String. Online tool TIMER was used to analyze the immune cells infiltration. R package maftools and GenVisR were applied to analyze frequently mutated genes and mutant-allele tumor heterogeneity (MATH) of PAAD. Survival of patients with pancreatic body/tail cancer was better than those with pancreatic head cancer (median survival, 24.05 vs 19.45 months, p = 0.048). And 496 significant DEGs (|log2 FoldChange| > 1.5,false discovery rate (FDR)

A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited.To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China.This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from China from the ChinaMAP database. Data were updated and analyzed in July 2021.Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups.A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort.In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.

Postoperative pancreatic fistula (POPF) is a major complication and main cause of mortality after pancreaticoduodenectomy (PD). Afferent loop decompression technique (ALDT) has theoretical feasibility to reduce the rate of POPF. The aim of this study is to determine whether ALDT is a protective factor for POPF. A total of 492 consecutive patients who underwent PD between January 2012 and December 2014 were identified from a prospective database. All data were extracted and events were judged based on medical records. Propensity score matching was conducted to balance several variables. Univariate and multivariate analyses were performed, respectively, to investigate the independent risk factors for pancreatic fistula. ALDT required a nasogastric tube with multiple side holes to be placed deep into the afferent jejunal limb. The rationale for this technique was to prevent pancreatic fistula by decreasing intraluminal pressure in the afferent jejunal loop by placement of the nasogastric tube and the application of continuous low-pressure suction after surgery. The total rate of POPF for the entire cohort was 30.7%, and ISGPS grade-A/B/C POPF rates were 18.1, 10.6 and 2.0%, respectively. In-hospital mortality was 1.6%. Among the 331 patients who received ALDT, 89 developed pancreatic leakage (26.9 vs. 38.5% for non-ALDT; P = 0.009) and eight developed biliary leakage (2.4 vs. 6.2% for non-ALDT; P = 0.035). Apart from ALDT, decreased preoperative ALT, soft pancreas, long operative time and tumour presence in the lower common bile duct (as opposed to the pancreas) were identified as other independent risk factors for POPF following multivariate logistic regression analysis. ALDT may reduce the incidence of POPF after PD.

Postoperative pancreatic fistula (POPF) is a major source of morbidity after pancreaticoduodenectomy (PD). The purpose of this retrospective study comparing 1-layer pancreaticojejunostomy (PJ) with 2-layer PJ after PD was to evaluate whether the 1-layer duct-to-mucosa PJ after PD can reduce the incidence of POPF. A total of 194 consecutive patients who underwent PD by one group of surgeons (led by Y.M.) from January 2011 to February 2014 were included in this study. Among those patients, 104 underwent 1-layer PJ (1-layer group), and 90 patients underwent 2-layer PJ (2-layer group). Preoperative clinicopathologic features, intraoperative parameters, and postoperative morbidity with a focus on POPF were compared between the 2 groups. The overall incidence of POPF was 19.6% (38 of 194 patients), and clinically relevant grade B and C POPF rates were 8.6% (16 of 194 patients) and 3.1% (6 of 194 patients), respectively. There were no differences in patient demographics and operation-related factors between the 2 groups. However, the incidence of POPF in the 1-layer group was significantly lower than in the 2-layer group [13.5% (14 of 104) of patients and 26.7% (24 of 90) of patients, respectively; P = 0.021]. The median postoperative hospital stay was also significantly shorter in the 1-layer group compared with the 2-layer group (13 versus 15 days, P = 0.035). One patient in the 2-layer group died of postoperative hemorrhage. One-layer duct-to-mucosa PJ is a simple and easy technique for pancreaticojejunal anastomosis after PD, and it can reduce the POPF rate in comparison with the 2-layer technique.

Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.

Background: Pancreatic solid pseudopapillary tumors (SPTs) are rare neoplasms with low-grade malignancy. The main treatment for them is surgical resection. However, some SPTs relapse after resection. The risk factors associated with the recurrences of resected SPTs remain controversial to date. We performed a systematic review and meta-analysis to identify the risk factors of the recurrences of pancreatic SPTs. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 2017. Studies that focused on the risk factors of postoperative relapses of pancreatic SPTs were enrolled. Combined ORs with 95% CIs were calculated to evaluate the effects of relevant factors investigated in eligible studies. Heterogeneity among combined results was assessed by Cochran's Q test and by the degree of inconsistency (I2). Statistical analyses were performed by Review Manager (version 5.3) using random effects models. Results: We included 10 studies, which enrolled 1091 patients. The pooled results suggested that patients with larger tumors (diameter > 5cm), lymphovascular invasion, lymph node metastasis, synchronous metastasis and positive margin were prone to suffer from the recurrences of SPTs. In addition, some factors like gender, location of tumors, perineural invasion, calcification and capsular invasion did not show any correlation with the relapses of resected SPTs. Conclusion: Factors including a larger tumor size (diameter > 5cm), lymphovascular invasion, lymph node metastasis, synchronous metastasis and positive margin may increase the risk of recurrences of resected pancreatic SPTs. All SPTs should be excised and patients with high-risk features should undergo a long-term follow-up.

Background Pathology is the gold standard for diagnosis of pancreatic cancer. Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that is not routine in developing countries, hence a cheap, reliable alternative is required. Aim To evaluate the effectiveness and safety of a new technique of intraoperative biopsy from pancreatic head mass. Methods Patients undergoing intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from January 2000 to June 2015 were included in this study. Following Kocher's maneuver, a biopsy was taken from the mass through the duodenum transluminally, using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens were obtained for intraoperative frozen section examination. Depending on the pathological results, a decision was taken to either perform pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass surgery, or to just terminate the operation. The malignancy status of the lesion was confirmed by postoperative pathological examination and/or long-term follow-up of the patients. Results A total of 525 patients were included. Intraoperative pathological reports revealed 436 malignant cases and 89 cases without evidence of malignancy. The sensitivity, specificity, false positive rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively. Complications occurred in 2 patients. Conclusion TLCB is a quick, safe, effective, and accurate method for intraoperative diagnosis method in patients with pancreatic head mass; it can provide reliable evidence for surgical decision-making.

Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis.

Purpose: Glucagonoma is an extremely rare neuroendocrine tumor arising from pancreatic islet cells. Although patients with glucagonoma manifest multiple typical symptoms, early diagnosis remains difficult due to the scarcity of this disease. Methods: In this study, we retrospectively screened the database of the pancreas center of Nanjing Medical University. A total of six cases diagnosed as glucagonoma during the past 17 years were included. Their clinical characteristics and treatments were reviewed. Results: The six patients consisted of four females and two males. Their median age at diagnosis was 48.7 years (range 35–77). The time from onset of symptoms to diagnosis of glucagonoma ranged from 1.3 months to >10 years. Common symptoms included necrotizing migratory erythema shown in six of six patients (100%), diabetes mellitus in five of six patients (83%), stomatitis in four of six patients (67%), and weight loss in four of six patients (67%). Plasma glucagon levels were elevated in all patients (range 245.6–1132.2 pg/mL; n

Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models. In human luminal tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was positively correlated with CD31-positive microvascular density, induced angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial cell tube formation in vitro. VASH2 expression was absent in the concentrated conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing luminal breast cancer cells. Further, VASH2 regulated the expression of fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2 neutralization in vitro. Additionally, dual luciferase reporter assay and Chromatin immunoprecipitation analysis results showed that FGF2 promoter was transcriptionally activated by VASH2 via histone modifications. In conclusion, VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms.

Introduction Few studies have compared patency rates of the different methods of venous reconstruction (VR) during a pancreatectomy. This study aimed to evaluate the patency rates and the clinical impact of various reconstruction methods. Methods For the meta-analysis, databases were systematically searched to identify studies reporting the outcomes of patients who underwent PVR/SMVR. For the retrospective study, clinical data were retrospectively analyzed from patients who underwent a pancreatectomy and VR between Feb. 2009 and Oct. 2015. Patency was assessed by CT and/or ultrasound. Results For the meta-analysis, the long-term patency rates of the primary repair group and the autologous graft group were significantly higher than that of the synthetic graft group. For the retrospective study, the reconstruction consisted of primary repair in 62 cases (89.8%) and synthetic grafting in 7 cases (10.1%). Synthetic grafting was more likely to cause acute thrombosis compared with primary repair for PVR/SMVR (85.7% versus 16.7%). Acute thrombosis was associated with decreased median survival (12 versus 6 months) and increased hazard of death. Late thrombosis and stenosis were not associated with survival or serious clinical impact. Median survival for the primary repair group and the synthetic grafting group was 12 and 7 months, respectively. Conclusion Primary repair following PVR/SMVR is preferred and can be achieved in most situations. Stenosis should be noted when with risk factors (long segmental and tension), but it produced little clinical impact. Synthetic grafting was associated with a higher thrombosis rate. Acute thrombosis is associated with increased mortality and decreased survival.