Mapping global new-onset, worsening, and resolution of diabetes following partial pancreatectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Partial pancreatectomy, commonly used for chronic pancreatitis, or pancreatic lesions, has diverse impacts on endocrine and metabolism system. The study aims to determine the global prevalence of new-onset, worsening, and resolution of diabetes following partial pancreatectomy. METHODS: The authors searched PubMed, Embase, Web of Science, and Cochrane Library from inception to October, 2023. DerSimonian-Laird random-effects model with Logit transformation was used. Sensitivity analysis, meta-regression, and subgroup analysis were employed to investigate determinants of the prevalence of new-onset diabetes. RESULTS: A total of 82 studies involving 13 257 patients were included. The overall prevalence of new-onset diabetes after partial pancreatectomy was 17.1%. Univariate meta-regression indicated that study size was the cause of heterogeneity. Multivariable analysis suggested that income of country or area had the highest predictor importance (49.7%). For subgroup analysis, the prevalence of new-onset diabetes varied from 7.6% (France, 95% CI: 4.3-13.0) to 38.0% (UK, 95% CI: 28.2-48.8, P <0.01) across different countries. Patients with surgical indications for chronic pancreatitis exhibited a higher prevalence (30.7%, 95% CI: 21.8-41.3) than those with pancreatic lesions (16.4%, 95% CI: 14.3-18.7, P <0.01). The type of surgical procedure also influenced the prevalence, with distal pancreatectomy having the highest prevalence (23.7%, 95% CI: 22.2-25.3, P <0.01). Moreover, the prevalence of worsening and resolution of preoperative diabetes was 41.1 and 25.8%, respectively. CONCLUSIONS: Postoperative diabetes has a relatively high prevalence in patients undergoing partial pancreatectomy, which calls for attention and dedicated action from primary care physicians, specialists, and health policy makers alike.

Laparoscopic versus open central pancreatectomy: a propensity score-matched analysis in a single centre.

PURPOSE: Laparoscopic central pancreatectomy (LCP) has been implemented in pancreatic surgery; however, open surgery is still the predominant approach for central pancreatectomy (CP). Our objective was to compare LCP with open CP (OCP). METHODS: Data were collected from patients with tumours located in the pancreatic neck and proximal body who underwent CP in the Department of Pancreatic Surgery West China Hospital from January 1, 2010, to June 30, 2019. A comparison between the LCP and OCP groups was performed. RESULTS: Fifteen patients underwent CP via the laparoscopic approach, and 96 patients underwent CP via the open approach. Using 1:2 propensity score matching (PSM), 12 patients in the LCP group were matched to 21 in the OCP group. Regarding safety, postoperative pancreatic fistula (POPF) was not significantly different between the two groups (13.3% vs. 12.5%, P = 1.000), even with PSM (16.7% vs. 14.3%, P = 1.000). However, regarding effectiveness, the operative time in the OCP group was significantly shorter than that in the LCP group before (307.0 ± 92.3 ml vs. 220.6 ± 63.6 ml, P < 0.000) and after (300.3 ± 90.2 ml vs. 212.7 ± 44.4 ml, P = 0.002) PSM. Regarding length of stay (LOS), there was no difference between the two groups before (13.1 ± 13.7 days vs. 12.7 ± 10.1 days, P = 0.376) and after PSM (14.4 ± 15.1 days vs. 14.5 ± 16.2 days, P = 0.985). The length of the resected pancreas was shorter in the OCP group than in the LCP group before PSM (50.0 ± 13.2 mm vs. 41.1 ± 11.1 mm, P = 0.043). However, there was no difference between the two groups after PSM (47.9 ± 12.5 mm vs. 37.9 ± 10.4 mm, P = 0.084). Moreover, the other variables showed no difference between the two groups before and after PSM. CONCLUSION: LCP can demonstrate similar safety and effectiveness to OCP, even in the early stages of the learning curve.

Single-minded homolog 2 as a potential prognostic signature and assessment of its correlation with immune cell infiltration in pancreatic cancer.

Single-minded homolog 2 (SIM2) has been identified as a potential contributor to the development of solid tumors. Despite this, there is a lack of comprehensive research regarding its biological role and underlying mechanism within pancreatic cancer (PC), as well as its prognostic impact. This study systematically evaluated the expression level and clinical significance of SIM2 in patients with PC using various databases, including The Cancer Genome Atlas, KM Plotter, and gene expression profiling interactive analysis. To investigate the relationship between SIM2 expression and immune cell infiltration, we conducted ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) analyses. Single-minded homolog 2 was up-regulated in patients with PC. Pancreatic cancer patients with higher SIM2 expression had poorer overall survival rates. Gene set enrichment analysis results suggested that SIM2 may have a significant impact on the progression of PC and the regulation of immune responses. According to the ssGSEA algorithm, SIM2 has a negative correlation with the levels of infiltrating TFH, mast cells, and pDC. Our study demonstrated that SIM2 serves as a biomarker, and is associated with both prognosis and immune infiltration in PC. This provides a solid foundation for future investigations into the precise role of SIM2 in the carcinogenesis and progression of PC.

Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement.

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

LncRNA GAS8-AS1 is a Novel Prognostic and Diagnostic Biomarker for Pancreatic Cancer.

BACKGROUND: LncRNA GAS8-AS1 inhibits thyroid carcinoma, but its function in other malignancies is unknown. The present study aimed to investigate the involvement of GAS8-AS1 in pancreatic cancer (PC). METHODS: The present study included 68 PC patients (38 males and 30 females, 42-66 years, 52.1 ± 4.5) and 62 healthy volunteers (28 males and 24 females, 43-67 years, 52.3 ± 4.9). Real-time quantitative PCR, transient cell transfection, and in vitro cell migration and invasion assays were applied for the research. RESULTS: The study showed that plasma GAS8-AS1 was lower in PC patients than in healthy controls. Downregulation of plasma GAS8-AS1 distinguished early-stage PC patients from healthy controls. Patients with low GAS8-AS1 plasma levels showed a significantly lower 5-year overall survival rate. Plasma miR-1179 levels were also significantly lower in PC patients than in healthy controls and were positively correlated with plasma GAS8-AS1 levels in PC patients but not healthy controls. GAS8-AS1 overexpression upregulated miR-1179, and MiR-1179 overexpression increased GAS8-AS1 level. Overexpression of both GAS8-AS1 and miR-1179 inhibited PC cell migration and invasion. CONCLUSION: GAS8-AS1 may promote PC by positively interacting with miR-1179.

Development and validation of a prediction model for deep vein thrombosis in older non-mild acute pancreatitis patients.

BACKGROUND: Deep vein thrombosis (DVT) may cause pulmonary embolus, leading to late deaths. The systemic inflammatory and hypercoagulable state of moderate and severe acute pancreatitis (non-mild acute pancreatitis, NMAP) patients may contribute to the development of venous thromboembolism. Accurate prediction of DVT is conducive to clinical decisions. AIM: To develop and validate a potential new prediction nomogram model for the occurrence of DVT in NMAP. METHODS: NMAP patient admission between 2013.1.1 and 2018.12.31 at the West China Hospital of Sichuan University was collected. A total of 220 patients formed the training set for nomogram development, and a validation set was constructed using bootstrapping with 100 resamplings. Univariate and multivariate logistic regression analyses were used to estimate independent risk factors associated with DVT. The independent risk factors were included in the nomogram. The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis, respectively. RESULTS: A total of 220 NMAP patients over 60 years old were enrolled for this analysis. DVT was detected in 80 (36.4%) patients. The final nomogram included age, sex, surgery times, D-dimer, neutrophils, any organ failure, blood culture, and classification. This model achieved good concordance indexes of 0.827 (95%CI: 0.769-0.885) and 0.803 (95%CI: 0.743-0.860) in the training and validation sets, respectively. CONCLUSION: We developed and validated a prediction nomogram model for DVT in older patients with NMAP. This may help guide doctors in making sound decisions regarding the administration of DVT prophylaxis.

Clinical study on cystogastrostomy and Roux-en-Y-type cystojejunostomy in the treatment of pancreatic pseudocyst: A single-center experience.

ABSTRACT: The main purpose is to compare the efficacy of cystogastrostomy (CG) and Roux-en-Y-type cystojejunostomy (RCJ) in the treatment of pancreatic pseudocyst (PPC), and to explore the risk factors of recurrence and complications after internal drainage.Two hundred eight patients undergoing either CG or RCJ for PPC Between January 1, 2013and February 1, 2019, at West China Hospital of Sichuan University were retrospectively analyzed. The cure rate, complication rate and related factors were compared between the 2 groups.Two hundred eight patients with PPC underwent either a CG (n = 119) or RCJ (n = 89). The median follow-up time was 42.7 months. Between the 2 cohorts, there were no significant differences in cure rate, reoperation rate, and mortality (all P > .05). The operative time, estimated intraoperative blood loss, install the number of drainage tubes and total expenses in CG group were lower than those in RCJ group (all P < .05). The Logistic regression analysis showed that over twice of pancreatitis' occurrence was were independent risk factor for recurrence after internal drainage of PPC (OR 2.760, 95% CI 1.006∼7.571, P = .049). Short course of pancreatitis (OR 0.922, 95% CI 0.855∼0.994, P = .035), and RCJ (OR 2.319, 95% CI 1.033∼5.204, P = .041) were independent risk factors for complications after internal drainage of PPC.Both CG and RCJ are safe and effective surgical methods for treating PPC. There were no significant differences in cure rate, reoperation rate, and mortality between the 2 groups, while the CG group had a short operation time, less intraoperative bleeding and less cost.

miR-25 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation by targeting ABI2.

MicroRNAs (miRNAs) are reported to play a critical role in the regulation of cancer cell proliferation; however, the role of microRNA-25 (miR-25) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the present study, the role of miR-25 in PDAC cell proliferation was investigated. Upregulated expression of miR-25 was found in PDAC tissues and cell lines by reverse transcription-quantitative PCR. Cell proliferation was significantly enhanced by overexpression of miR-25 as shown by CCK-8 assay results. Meanwhile, overexpression of miR-25 also promoted G1-to-S phase transition of the cell cycle in Aspc-1 cells via flow cytometry analysis. However downregulation of miR-25 inhibited the tumor cell proliferation and cell cycle transition. Online software was used to predict the target gene for miR-25 and luciferase reporter assay confirmed that Abl interactor 2 (ABI2) was a target of miR-25 via direct binding of its 3' untranslated region with miR-25. Moreover, results of the western blot analysis demonstrated that miR-25 negatively regulated the expression of ABI2 at the protein level. In addition, introduction of ABI2 mRNA into cells overexpressing miR-25 attenuated the carcinogenic effects of miR-25. In conclusion, these findings demonstrate that miR-25 plays an oncogenic role and promotive role in PDAC cell proliferation via targeting of ABI2.

Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF­ß signaling.

LINC01638 is a long non­coding RNA (lncRNA) with an oncogenic role in breast cancer, while its involvement in other malignancies is unknown. This study was performed to investigate the potential role of LINC01638 in pancreatic ductal adenocarcinoma (PDAC). The expression of LINC01638 was determined via reverse transcription­quantitative polymerase chain reaction analysis, whereas the levels of transforming growth factor­ß1 (TGF­ß1) in plasma were measured via ELISA. Receiver operating characteristic curve analysis was conducted to determine the diagnostic value of LINC01638. Additionally, the migratory and invasive abilities of cells were evaluated via Transwell migration and invasion assays. In the present study, LINC01638 was significantly upregulated in tumor tissues compared with adjacent healthy tissues in the majority of patients with PDAC. Plasma levels of LINC01638 were significantly higher in patients with PDAC compared with in healthy controls. In effect, upregulation of plasma LINC01638 distinguished patients with PDAC from healthy controls in receiver operating characteristic analysis. Plasma levels of LINC01638 and TGF­ß1 were positively correlated in patients with PDAC, but not in healthy controls. LINC01638 overexpression increased TGF­ß1 expression, while silencing of LINC01638 using short hairpin RNA (shRNA) led to reduced TGF­ß1 expression in a PDAC cell line. LINC01638 overexpression promoted, while shRNA silencing inhibited, migration and invasion of cell of a PDAC cell line. Treatment with exogenous TGF­ß1 attenuated the inhibitory effect of LINC01638 shRNA silencing on cancer cell migration and invasion. It is concluded that LINC01638 lncRNA may be involved in the migration and invasion of PDAC cells via regulation of TGF­ß1.

Total pancreatectomy compared with pancreaticoduodenectomy: a systematic review and meta-analysis.

Aim: To assess whether total pancreatectomy (TP) is as feasible, safe, and efficacious as pancreaticoduodenectomy (PD). Materials and Methods: Major databases, including PubMed, EMBASE, Science Citation Index Expanded, Scopus and the Cochrane Library, were searched for studies comparing TP and PD between January 1943 and June 2018. The meta-analysis only included studies that were conducted after 2000. The primary outcomes were morbidity and mortality. Pooled odds ratios (ORs), weighted mean differences (WMDs) or hazard ratios (HRs) with 95 percent confidence intervals (CIs) were calculated using fixed effects or random effects models. The methodological quality of the included studies was evaluated by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Results: In total, 45 studies were included in this systematic review, and 5 non-randomized comparative studies with 786 patients (TP: 270, PD: 516) were included in the meta-analysis. There were no differences in terms of mortality (OR: 1.44, 95% CI: 0.66-3.16; P=0.36), hospital stay (WMD: -0.60, 95% CI: -1.78-0.59; P=0.32) and rates of reoperation (OR: 1.12; 95% CI: 0.55-2.31; P=0.75) between the two groups. In addition, morbidity was not significantly different between the two groups (OR: 1.41, 95% CI: 1.01-1.97; P=0.05); however, the results showed that the TP group tended to have more complications than the PD group. Furthermore, the operation time (WMD: 29.56, 95% CI: 8.23-50.89; P=0.007) was longer in the TP group. Blood loss (WMD: 339.96, 95% CI: 117.74-562.18; P=0.003) and blood transfusion (OR: 4.86, 95% CI: 1.93-12.29; P=0.0008) were more common in the TP group than in the PD group. There were no differences in the long-term survival rates between the two groups. Conclusion: This systematic review and meta-analysis suggested that TP may not be as feasible and safe as PD. However, TP and PD may have the same efficacy.

Linc-pint inhibits early stage pancreatic ductal adenocarcinoma growth through TGF-ß pathway activation.

Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a newly identified long non-coding RNA, which has demonstrated antitumor activities in various types of cancer. The present study aimed to investigate the role of Linc-pint in pancreatic ductal adenocarcinoma (PDAC). Plasma samples from patients with PDAC, and PDAC and normal cell lines were used in the study. Gene expression was analyzed by reverse transcription-quantitative polymerase chain reaction. Western blotting was used to assess protein level. Transforming growth factor ß1 (TGF-ß1) plasma level was determined by ELISA. Cancer cell proliferation was measured in vitro with the Cell Counting Kit-8 assy. The results demonstrated that Linc-pint plasma levels were significantly lower in patients with stage 0-1 PDAC compared with healthy controls. In addition, Linc-pint downregulation effectively distinguished patients with PDAC from healthy controls. Linc-pint and TGF-ß1 plasma levels were positively correlated in patients with PDAC but not in healthy controls. Furthermore, Linc-pint overexpression upregulated TGF-ß1 expression in PDAC cells but not in normal pancreatic ductal cells; however, exogenous TGF-ß1 exhibited no significant effects on Linc-pint expression. Linc-pint overexpression and TGF-ß1 both inhibited PDAC cell proliferation, whereas treatment with a TGF-ß inhibitor reduced their inhibitory effects on cell proliferation. In conclusion, results from the present study suggested that Linc-pint may inhibit early stage PDAC growth through TGF-ß pathway activation.

The oncological safety in minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

The safety of minimally invasive distal pancreatectomy (MIDP) and open distal pancreatectomy (ODP) regarding oncological outcomes of pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. Therefore, the aim of this study was to examine the oncological safety of MIDP and ODP for PDAC. Major databases including PubMed, Embase, Science Citation Index Expanded, and the Cochrane Library were searched for studies comparing outcomes in patients undergoing MIDP and ODP for PDAC from January 1994 to August 2018. In total, 11 retrospective comparative studies with 4829 patients (MIDP: 1076, ODP: 3753) were included. The primary outcome was long-term survival, including 3-year overall survival (OS) and 5-year OS. The 3-year OS (hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.89, 1.21; P = 0.66) and 5-year OS (HR: 0.91, 95% CI: 0.65, 1.28; P = 0.59) showed no significant differences between the two groups. Furthermore, the positive surgical margin rate (weighted mean difference (WMD): 0.71, 95% CI: 0.56, 0.89, P = 0.003) was lower in the MIDP group. However, patients in the MIDP group had less intraoperative blood loss (WMD: -250.03, 95% CI: -359.68, -140.39; P < 0.00001), a shorter hospital stay (WMD: -2.76, 95% CI: -3.73, -1.78; P < 0.00001) and lower morbidity (OR: 0.57, 95% CI: 0.46, 0.71; P < 0.00001) and mortality (OR: 0.50, 95% CI: 0.31, 0.81, P = 0.005) than patients in the ODP group. The limited evidence suggested that MIDP might be safer with regard to oncological outcomes in PDAC patients. Therefore, future high-quality studies are needed to examine the oncological safety of MIDP.

MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy.

Ribonucleotide reductase subunit M2 (RRM2) acts as an important gemcitabine resistance-related gene in pancreatic cancer (PC). Here, we aimed to investigate the potential microRNA that regulates gemcitabine chemosensitivity by targeting RRM2 and explores the clinical significance of candidate miRNA in PC. MTT assay and Western blot analysis revealed that long-time gemcitabine treatment in PC cells induced drug resistance and RRM2 increase, and silence of RRM2 blocked gemcitabine resistance. Among the predicted eight RRM2-related microRNAs, the expression of miR-20a-5p showed the most significant discrepancy between gemcitabine-resistant cells and parental cells. Furthermore, the Dual-Luciferase reporter gene assay indicated that miR-20a-5p directly targeted RRM2 3'UTR, thus inhibited expression of RRM2 and overcame gemcitabine resistance of PC cells. Retrospective study suggested that plasma miR-20a-5p level was correlated with gemcitabine resistance in PC patient. ROC curve showed that miR-20a-5p abundant level might predict gemcitabine resistance with an AUC of 89% (P<0.0001). Additionally, the PFS of patients with high and low expression levels miR-20a-5p was 2.8 and 4.5 months (P<0.001), respectively. Taken together, our results suggests that miR-20a-5p regulated gemcitabine chemosensitivity by targeting RRM2 in PC cells and could serve as a predictor for predicting the efficacy of gemcitabine-based chemotherapy in first-line treatment of PC patients.

Timing of Laparoscopic Cholecystectomy After Mild Biliary Pancreatitis: A Systematic Review and Meta-Analysis.

AIM: To compare the safety of cholecystectomy in early laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC). METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library for studies that were published from January 1992 to March 2017. We included studies on patients with mild biliary pancreatitis and that reported the timing of cholecystectomy and the number of complications, readmissions, and conversion to open cholecystectomy. Moreover, we assessed the quality and bias risks of the included studies. RESULTS: After screening 4651 studies, we included 3 randomized clinical trials and 10 retrospective studies. The included studies described 2291 patients, of whom 1141 (49.8%) underwent ELC and 1150 (50.2%) underwent DLC. The reported rate of complications for ELC (6.8%) was lower than that for DLC (13.45%). The reported rate of readmission for ELC was lower than that for DLC. The length of hospital stay was longer with DLC than with ELC. ELC and DLC did not have significantly different rates of conversion to open cholecystectomy and duration of surgery. CONCLUSION: This meta-analysis provides evidence that ELC is better than DLC in many aspects for acute mild pancreatitis patients undergoing laparoscopic cholecystectomy. ELC associated with few complications and readmissions, as well as a short length of hospital stay.