Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5-year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT-PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

Biological functions and clinical significance of tRNA-derived small fragment (tsRNA) in tumors: Current state and future perspectives.

A new class of noncoding RNAs, tsRNAs are not only abundant in humans but also have high tissue specificity. Recently, an increasing number of studies have explored the correlations between tsRNAs and tumors, showing that tsRNAs can affect biological behaviors of tumor cells, such as proliferation, apoptosis and metastasis, by modulating protein translation, RNA transcription or posttranscriptional regulation. In addition, tsRNAs are widely distributed and stably expressed, which endows them with broad application prospects in diagnosing and predicting the prognosis of tumors, and they are expected to become new biomarkers. However, notably, the current research on tsRNAs still faces problems that need to be solved. In this review, we describe the characteristics of tsRNAs as well as their unique features and functions in tumors. Moreover, we also discuss the potential opportunities and challenges in clinical applications and research of tsRNAs.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). CONCLUSION: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

The incidence and risk factors of marginal ulcers in the short and medium term in symptomatic post-pancreaticoduodenectomy patients ---- single-center experience.

BACKGROUND: Marginal ulcer (MU) is one of the postoperative complications of pancreaticoduodenectomy (PD), which needs particular attention in postoperative treatments. METHODS: The data of 190 patients who underwent PD and follow-up gastroscopic review due to upper GI symptoms within two years were retrospectively analyzed. The incidence of MU and risk factors were analyzed based on personal history, surgical procedure, past medical history, postoperative complications, and other relevant indicators. RESULTS: The proportion of MU in patients who underwent endoscopic follow-up for upper gastrointestinal symptoms in the postoperative period in this cohort was 10.5% (20/190). Advanced age (69y vs. 59y, P â€‹= â€‹0.012), alcohol consumption (20% vs. 8.2%, P â€‹= â€‹0.03), and cigarette smoking (35% vs. 14.7%, P â€‹= â€‹0.022) were associated with an increased incidence of MU. Longer surgery time (276.5min vs. 240min, P â€‹= â€‹0.049), postoperative bleeding (10% vs. 1.8%, P â€‹= â€‹0.030), and failure to take antacid regularly postoperatively (75% vs. 97.1%, P â€‹= â€‹0.000) would increase the risk of MU; taking antacid regularly was an independent protective factor for postoperative anastomotic ulceration (OR: 0.091, CI: 0.022-0.383, P â€‹= â€‹0.001). CONCLUSION: Advanced age, alcohol consumption, smoking, longer operation time, or postoperative extraluminal hemorrhage are associated with MU. Regular use of antacids is an independent protective factor against the development of MU.

Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4-HDAC4-RUNX2-GAMT-mediated apoptosis.

BACKGROUND: Pancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC. METHODS: qRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues. The function of circCGNL1 in PC progression was examined both in vitro and in vivo. circCGNL1-interacting proteins were identified by performing RNA pulldown, co-immunoprecipitation, GST-pulldown, and dual-luciferase reporter assays. RESULTS: Overexpressing circCGNL1 inhibited PC proliferation via promoting apoptosis. CircCGNL1 interacted with phosphatase nudix hydrolase 4 (NUDT4) to promote histone deacetylase 4 (HDAC4) dephosphorylation and subsequent HDAC4 nuclear translocation. Intranuclear HDAC4 mediated RUNX Family Transcription Factor 2 (RUNX2) deacetylation and thereby accelerating RUNX2 degradation. The transcription factor, RUNX2, inhibited guanidinoacetate N-methyltransferase (GAMT) expression. GAMT was further verified to induce PC cell apoptosis via AMPK-AKT-Bad signaling pathway. CONCLUSIONS: We discovered that circCGNL1 can interact with NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation, subsequently activating HDAC4-RUNX2-GAMT-mediated apoptosis to suppress PC cell growth. These findings suggest new therapeutic targets for PC.

High pyroptosis activity in pancreatic adenocarcinoma: poor prognosis and oxaliplatin resistance.

BACKGROUND: Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal adenocarcinoma (PDAC) remains further exploration. METHODS: A TCGA-PDAC cohort was enrolled for bioinformatics analysis to investigate the effect of pyroptosis on the prognosis and drug sensitivity of patients. PA-TU-8988T and CFPAC-1 cells were selected for investigating the role of GSDMC in PDAC. RESULTS: A distinct classification pattern of PDAC mediated by 21 pyroptosis-related genes (PRGs) was identified. It was suggested that higher pyroptosis activity was associated with poor prognosis of patients and higher tumor proliferation rates. We further established a prognostic model based on three PRGs (GSDMC, CASP4 and NLRP1) and the TCGA-PDAC cohort was classified into low and high-risk subgroups. It is noteworthy that the high-risk group showed significantly higher tumor proliferation rates and was proved to be highly correlated with oxaliplatin resistance. Further experiments suggested that overexpression of GSDMC promoted the proliferation and oxaliplatin resistance of PA-TU-8988T cells in vitro and vivo, while downregulation of GSDMC showed opposite effects in CFPAC-1 cells. Finally, we found that the activation of pentose phosphate pathway (PPP) was the mechanism by which GSDMC overexpression promoted the proliferation and oxaliplatin resistance of pancreatic cancer cells. CONCLUSIONS: In this study, we found that higher pyroptosis activity is associated with worse prognosis and oxaliplatin resistance of PDAC patients. In addition, as a core effector of pyroptosis, GSDMC promoted proliferation and oxaliplatin resistance of pancreatic cancer cells, which will provide new therapeutic target for PDAC patients.

Comprehensive prognostic and immune analysis of a glycosylation related risk model in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a malignant tumor with extremely poor prognosis, exhibiting resistance to chemotherapy and immunotherapy. Nowadays, it is ranked as the third leading cause of cancer-related mortality. Glycation is a common epigenetic modification that occurs during the tumor transformation. Many studies have demonstrated a strong correlation between glycation modification and tumor progression. However, the expression status of glycosylation-related genes (GRGs) in PC and their potential roles in PC microenvironment have not been extensively investigated. METHOD: We systematically integrated RNA sequencing data and clinicopathological parameters of PC patients from TCGA and GTEx databases. A GRGs risk model based on glycosylation related genes was constructed and validated in 60 patients from Pancreatic biobank via RT-PCR. R packages were used to analyze the relationships between GRGs risk scores and overall survival (OS), tumor microenvironment, immune checkpoint, chemotherapy drug sensitivity and tumor mutational load in PC patients. Panoramic analysis was performed on PC tissues. The function of B3GNT8 in PC was detected via in vitro experiments. RESULTS: In this study, we found close correlations between GRGs risk model and PC patients' overall survival and tumor microenvironment. Multifaceted predictions demonstrated the low-risk cohort exhibits superior OS compared to high-risk counterparts. Meanwhile, the low-risk group was characterized by high immune infiltration and may be more sensitive to immunotherapy or chemotherapy. Panoramic analysis was further confirmed a significant relationship between the GRGs risk score and both the distribution of PC tumor cells as well as CD8 + T cell infiltration. In addition, we also identified a unique glycosylation gene B3GNT8, which could suppress PC progression in vitro and in vivo. CONCLUSION: We established a GRGs risk model, which could predict prognosis and immune infiltration in PC patients. This risk model may provide a new tool for PC precision treatment.

A Risk Score for Predicting the Necessity of Surgical Necrosectomy in the Treatment of Infected Necrotizing Pancreatitis.

BACKGROUND: For infected necrotizing pancreatitis (INP), percutaneous catheter drainage (PCD) is now widely acknowledged as the initial intervention in a step-up approach, followed, if necessary, by minimally invasive necrosectomy or even open pancreatic necrosectomy. However, an overemphasis on PCD may cause a patient's condition to deteriorate, leading to missed surgical opportunities or even death. This study aimed to develop a simple and convenient scoring tool for assessing the need for surgery in INP patients who received PCD procedures. METHODS: In an observational study conducted between April 2015 and December 2020, PCD was utilized as the initial step to treat 143 consecutive INP patients. A surgical necrosectomy was performed when the patient failed to respond. Risk factors of PCD failure (i.e., need for surgical necrosectomy) were identified by multivariate logistic regression models. An integer-based risk scoring tool was developed using the ß coefficients derived from the logistic regression model. RESULTS: In 62 (43.4%) patients, PCD was successful, while the remaining 81 (56.6%) individuals required subsequent surgical necrosectomy. In the multivariate model, organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume were associated with a need for surgical necrosectomy. A predictive scoring tool based on these four factors demonstrated an area under the receiver operating characteristic curve (AUC) of 0.893. Under the scoring tool, a total score of 4 or more indicates a high possibility of surgical necrosectomy being required (at least 80%). Using the coordinates of the receiver operating characteristic curve (ROC), the sensitivity and specificity at this threshold are 0.802 and 0.903, respectively. CONCLUSIONS: A risk score model integrating organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume can identify INP patients at high risk for necrosectomy. The straightforward risk assessment tool assists clinicians in stratifying INP patients and making more judicious medical decisions.

Translation and validation of the Pancreatic Cancer Disease Impact score for Chinese patients with pancreatic cancer: A methodological and cross-sectional study.

Objective: We aimed to establish and validate the Chinese version of the Pancreatic Cancer Disease Impact (C-PACADI) score for Chinese patients with pancreatic cancer (PC). Methods: This was a methodological and cross-sectional study. We established the C-PACADI score following Beaton's translation guidelines and then included 209 patients with PC to evaluate C-PACADI's reliability and validity. Results: The Cronbach's alpha coefficient of the C-PACADI score was 0.822. The correlation coefficient between "skin itchiness" score and the total score was 0.224, while the correlation coefficients ranged from 0.515 to 0.688 (P â€‹< â€‹0.001) for all the other items. The item content validity index and the scale content validity index, evaluated by eight experts were 0.875 and 0.98, respectively. Regarding concurrent validity, the total score of the C-PACADI score was moderately correlated with the EuroQol-5D (EQ-5D) index and the EQ-5D VAS score (r â€‹= â€‹-0.738, P â€‹< â€‹0.01; r â€‹= â€‹-0.667, P â€‹< â€‹0.01, respectively); the individual-item scores of C-PACADI on pain/discomfort, anxiety, loss of appetite, fatigue, and nausea were strongly associated with the corresponding symptoms of the Edmonton Symptom Assessment System scale (r ranged from 0.879 to 0.916, P â€‹< â€‹0.01). The known-group validity was demonstrated by C-PACADI's ability to detect significant symptom differences between groups stratified by treatment modalities (P â€‹< â€‹0.05) and health status (P â€‹< â€‹0.001). Conclusions: The C-PACADI score is a suitable disease-specific tool for measuring the prevalence and severity of multiple symptoms in the Chinese population with PC.

Management and Outcome of Blunt Pancreatic Trauma: A Retrospective Cohort Study.

BACKGROUND: Pancreatic injury is rare, but it has a high mortality rate and its optimal treatment remains controversial. This study aimed to evaluate the clinical characteristics, management strategies, and outcomes of patients with blunt pancreatic injury. METHODS: This retrospective cohort study was performed on patients with a confirmed blunt pancreatic injury who were admitted to our hospital from March 2008 to December 2020. The clinical characteristics and outcomes of patients receiving different management strategies were compared. The risk factors for in-hospital mortality were evaluated by performing a multivariate regression analysis. RESULTS: A total of 98 patients diagnosed with blunt pancreatic injury were identified, with 40 patients having undergone nonoperative treatment (NOT) and 58 patients having undergone surgical treatment (ST). The overall in-hospital deaths were 6 (6.1%), including 2 (5.0%) and 4 (6.9%) in the NOT and ST groups, respectively. Pancreatic pseudocysts occurred in 15 (37.5%) and 3 (5.2%) of the NOT and ST groups, respectively, showing a significant difference between the two groups (P < 0.001). In the multivariate regression analysis, concomitant duodenal injury (OR = 14.42, 95% CI 1.27-163.52; P = 0.031) and sepsis (OR = 43.47, 95% CI, 4.15-455.75; P = 0.002) were independently associated with in-hospital mortality. CONCLUSIONS: Except for the higher incidence of pancreatic pseudocysts in the NOT group than in the ST group, there were no significant differences in the other clinical outcomes between the two groups. Concomitant duodenal injury and sepsis were the risk factors for in-hospital mortality.

Risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: a comprehensive systematic review and meta-analysis.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). However, its risk factors are still unclear. This meta-analysis aimed to identify the potential risk factors of DGE among patients undergoing PD or PPPD. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrial.gov for studies that examined the clinical risk factors of DGE after PD or PPPD from inception through 31 July 2022. We pooled odds ratios (ORs) with 95% CIs using random-effects or fixed-effects models. We also performed heterogeneity, sensitivity, and publication bias analyses. RESULTS: The study included a total of 31 research studies, which involved 9205 patients. The pooled analysis indicated that out of 16 nonsurgical-related risk factors, three risk factors were found to be associated with an increased incidence of DGE. These risk factors were older age (OR 1.37, P =0.005), preoperative biliary drainage (OR 1.34, P =0.006), and soft pancreas texture (OR 1.23, P =0.04). On the other hand, patients with dilated pancreatic duct (OR 0.59, P =0.005) had a decreased risk of DGE. Among 12 operation-related risk factors, more blood loss (OR 1.33, P =0.01), postoperative pancreatic fistula (POPF) (OR 2.09, P <0.001), intra-abdominal collection (OR 3.58, P =0.001), and intra-abdominal abscess (OR 3.06, P <0.0001) were more likely to cause DGE. However, our data also revealed 20 factors did not support stimulative factors influencing DGE. CONCLUSION: Age, preoperative biliary drainage, pancreas texture, pancreatic duct size, blood loss, POPF, intra-abdominal collection, and intra-abdominal abscess are significantly associated with DGE. This meta-analysis may have utility in guiding clinical practice for improvements in screening patients with a high risk of DGE and selecting appropriate treatment measures.

Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice.

Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/- (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1ß. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.

Perioperative safety and prognosis following parenchyma-preserving surgery for solid pseudopapillary neoplasm of the pancreas.

BACKGROUND/OBJECTIVES: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN). METHODS: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated. RESULTS: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration. CONCLUSIONS: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow.

The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer.

Background: Pancreatic cancer (PC) is a malignant cancer with poor prognosis and high mortality rate. Sine oculis homeobox homolog 1 (SIX1) participates in the development of many cancers. However, the function of SIX1 in PC is not fully understood. Methods: SIX1 expression was determined using immunohistochemistry in PC tissues and cell lines. Glucose consumption, lactate production, and ATP assays were used to detect the function of SIX1. PC cells and NK cells were cocultured to study the effect of SIX1 overexpression in PC cells on NK cell function. Chromatin immunoprecipitation (ChIP) assays were used to study the relationship between SIX1 and lactate dehydrogenase A (LDHA). A series of in vitro and in vivo assays were further applied to elucidate the important role of the SIX1/LDHA axis in metabolism and NK cell dysfunction in PC. Results: SIX1 was significantly upregulated in PC tissue; SIX1 overexpression promoted the glycolysis capacity of PANC-1 and CFPAC-1 cells and resulted in NK cell dysfunction after the NK cells had been cultured with PC cells. LDHA inhibitor partially restored the promotion of PC caused by SIX1 overexpression. According to ChIP assays, SIX1 directly binds to the LDHA promoter region. Moreover, LDHA inhibitor and lactate transporter blocker treatment promoted the function of NK cells cocultured with PC cells. In vivo experiments yielded the same results. Conclusion: The SIX1/LDHA axis promotes lactate accumulation and leads to NK cell dysfunction in PC.

Cancer-testis gene STK31 is regulated by methylation and promotes the development of pancreatic cancer.

BACKGROUD: Pancreatic cancer (PC) is a highly invasive malignancy with extremely poor prognosis. STK31 has been identified as a cancer-testis (CT) gene, but its function in PC has not been elucidated well. METHODS: The effect of STK31 on cell proliferation, migration and invasion was investigated by in vitro and in vivo experiments and total RNA sequencing and targeted bisulfite sequencing was applied to explore the potential regulatory mechanisms of STK31 in PC. RESULTS: By analysis of tissue samples and the clinicopathologic features, we found that STK31 was reactivated in PC and associated with poor prognosis. In addition, the vitro and vivo studies indicated that STK31 could promote PC progression by facilitating cell proliferation, migration and invasion, and the indication. Targeted Bisulfite Sequencing showed that STK31 was regulated by methylation. Furthermore, the results of total RNA sequencing suggested that STK31 was closely related to signal transduction, metabolism, and the immune system. CONCLUSIONS: This study demonstrates that STK31, as a CT gene, can promote the development of PC and is regulated by methylation. STK31 could be considered as a potential therapeutic target for PC.

A histopathological study of artery wall involvement in pancreatic cancer surgery.

PURPOSE: This study aims to study the depth of artery wall tumour invasion in patients undergoing surgery for pancreatic ductal adenocarcinoma. METHODS: Specimens from 47 pancreatic cancer patients with major arterial (splenic, SA; celiac, CA; common hepatic, CHA) invasion were examined: 45 left (distal) pancreatectomies, including 11 celiac artery resections, and two total pancreatectomies. Dissection of tumour-invaded arteries in 25 fresh specimens was attempted ex vivo using the sub-adventitial dissection technique (SDT). Tumour invasion of 66 arteries was graded using the tumour-free distance (TFD) from the external elastic lamina (EEL): 0 = no arterial invasion; I = TFD ≥ 1 mm; II = TFD < 1 mm; and grade III = EEL invasion. RESULTS: AJCC TNM staging was IA = 1 (2%), IB = 4 (9%), IIA = 5 (11%), IIB = 17(36%) and III = 20 (43%). Grade III tumour invasion was found in 17/47(36%) SAs, in 5/11 (45%) CAs and in 1/8 (13%) CHAs (p = 0.318). Attempted ex vivo SDT undertaken in 33 arteries from 25 specimens was complete in 16 and incomplete in 17 arteries. The median (IQR) TFD was 0.97 (0.11-2.54) mm in dissected and 0.14 (0.10, 0.14) mm in non-dissected SAs (p = 0.034). EEL tumour invasion occurred in 0/12 (0%) dissected compared to 7/13 (54%) non-dissected SAs (p = 0.005). Grades 0, I, II and III invasion were found in four (33%), two (17%) and six (50%), respectively, of 12 dissected SAs and grades II and III in six 6 (46%) and seven (54%), respectively, of 13 non-dissected SAs (p = 0.002). CONCLUSIONS: The grading system described may form the basis for classification to further develop arterial dissection techniques for pancreatic cancer.

Suppressive effect of YY1-mediated RGS22 regulation on the proliferation, migration and invasion of pancreatic ductal adenocarcinoma.

Regulator of G-protein signaling 22 (RGS22) is specifically expressed in the testis and in tumors of epithelial origin, but the expression and role of RGS22 in pancreatic cancer are unclear. In this study, 52 pairs of pancreatic ductal adenocarcinoma (PDAC) and adjacent non-neoplastic tissue samples with the corresponding clinical data were used to examine the expression of RGS22 and its relationship with PDAC prognosis. The findings showed that the expression of RGS22 was higher in the PDAC tissues than in the adjacent non-tumorous tissues and its expression was associated with the degree of blood vessel invasion. The in vitro experiments with PDAC cell lines and a normal control cell line showed that the proliferation, invasion, and metastasis of PDAC cells were suppressed by RGS22 overexpression and enhanced by RGS22 knockdown. The in vivo effect of RGS22 on PDAC xenografts was studied using subcutaneous implantation of tumor cells in BALB/cA-nu mice, and the results corroborated the in vitro findings. Analysis of the regulators of RGS22 showed that it was positively regulated by the transcription factor Yin Yang-1 (YY1). Thus, YY1-mediated RGS22 regulation suppressed the proliferation, migration, and invasion of PDAC.

Targeting pancreatic stellate cells in chronic pancreatitis: Focus on therapeutic drugs and natural compounds.

Chronic pancreatitis (CP) is a precancerous illness linked to pancreatic ductal adenocarcinoma (PDAC), although the evolutionary mechanism is uncertain. CP is distinguished by severe fibrosis caused by the activation of pancreatic stellate cells (PSCs). The current clinical therapeutic protocol for CP lacks specific therapeutic medicines for the prevention and suppression of inflammation and fibrosis aggravating in CP. More research on specifically targeting PSCs would help facilitate the development of novel therapies for pancreatic fibrosis. Notably, using natural compounds from medicinal plants as new antifibrotic agents has become a focus of recent research and is widely employed as an alternative and complementary approach. Our goal was to shed light on the role of PSCs in the development of CP and provide a focused update on the new potential therapeutic strategies against PSCs in CP models. Future studies can refer to these possible strategies for drug design, bioavailability, pharmacokinetics, and other issues to obtain better clinical outcomes for treating CP.

Laparoscopic treatment for an intrapancreatic accessory spleen: A case report.

Malignant pancreatic tumors have early metastasis, aggressive behavior and poor prognosis. Surgeons often need to judge whether a patient needs prompt surgery when a pancreatic lesion is found. The accessory spleen is a congenital developmental malformation rather than a tumor and does not require surgical resection. Here, we report a 47-year-old man who underwent routine gastroscopic examination, and a submucosal eminence of the duodenal bulb was detected. The patient was asymptomatic and laboratory tests were unremarkable. Duodenal neuroendocrine neoplasm (G2) was considered following endoscopic submucosal dissection (ESD). Further examination showed a lesion in the tail of the pancreas and multiple accessory spleens. The lesion in the tail of the pancreas was Ga-68 positive and was highly considered a pancreatic neuroendocrine tumor (pNET). Based on this clinical evidence, laparoscopic spleen-preserving distal pancreatectomy (Kimura) was performed. However, the results of the postoperative pathological diagnosis indicated an intrapancreatic accessory spleen (IPAS). Given the findings of this case, we should explore more accurate diagnostic methods for IPAS to avoid unnecessary surgery.