Characterization of Pancreatic Fistula after Post-pancreatectomy Acute Pancreatitis.

OBJECTIVE: This study aimed to investigate the clinical significance and risk factors of postoperative pancreatic fistula (POPF) after post-pancreatectomy acute pancreatitis (PPAP) in patients who underwent pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: PPAP has been recognized as a critical factor in the pathophysiology of POPF after PD. METHODS: A total of 817 consecutive patients who underwent elective PD between January 2020 and June 2022 were included. PPAP and POPF were defined in accordance with the International Study Group for Pancreatic Surgery (ISGPS) definitions. Multivariate logistic analyses were performed to investigate the risk factors for POPF. Comparisons between PPAP-associated POPF and non-PPAP-associated POPF were made to further characterize this intriguing complication. RESULTS: Overall, 159 (19.5%) patients developed POPF after PD, of which 73 (45.9%) occurred following PPAP, and the remaining 86 (54.1%) had non-PPAP-associated POPF. Patients with PPAP-associated POPF experienced significantly higher morbidity than patients without POPF. Multivariate analyses revealed distinct risk factors for each POPF type. For PPAP-associated POPF, independent risk factors included estimated blood loss >200 mL (OR 1.93), MPD ≤3 cm (OR 2.88), and soft pancreatic texture (OR 2.01), largely overlapping with FRS (Fistula Risk Score) elements. On the other hand, non-PPAP-associated POPF was associated with age >65 years (OR 1.95), male (OR 2.10), and MPD ≤3 cm (OR 2.57). Notably, among patients with PPAP, the incidence of POPF consistently hovered around 50% regardless of the FRS stratification. CONCLUSIONS: PPAP-associated POPF presents as a distinct pathophysiology in the development of POPF after PD, potentially opening doors for future prevention strategies targeting the early postoperative period.

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.

Robotic versus open pancreatoduodenectomy in patients with pancreatic duct adenocarcinoma after the learning curve: a propensity score-matched analysis.

BACKGROUND: Studies have demonstrated that the learning curve plays an important role in robotic pancreatoduodenectomy (RPD). Although improved short-term outcomes of RPD after the learning curve have been reported compared to open pancreatoduodenectomy (OPD), there is a lack of long-term survival analyses. METHODS: Patients who underwent curative intended RPD and OPD for pancreatic duct adenocarcinoma (PDAC) between January 2017 and June 2020 were retrospectively reviewed. A 1:2 propensity score matching (PSM) analysis was performed to balance the baseline characteristics between the RPD and OPD groups. RESULTS: Of the 548 patients (108 RPD and 440 OPD), 103 RPD patients were matched with 206 OPD patients after PSM. There were 194 (62.8%) men and 115 (37.2%) women, with a median age of 64 (58-69) years. The median overall survival (OS) in the RPD group was 33.2 months compared with 25.7 months in the OPD group (p = 0.058, log-rank). The median disease-free survival (DFS) following RPD was longer than the OPD (18.5 vs. 14.0 months, p = 0.011, log-rank). The RPD group has a lower incidence of local recurrence compared the OPD group (36.9% vs. 51.2%, p = 0.071). Multivariate Cox analysis demonstrated that RPD was independently associated with improved OS (HR 0.70, 95% CI 0.52-0.94, p = 0.019) and DFS (HR 0.66, 95% CI 0.50-0.88, p = 0.005). CONCLUSION: After the learning curve, RPD had improved oncologic outcomes in PDAC patients compared to OPD. Future prospective randomized clinical trials will be required to validate these findings.

BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1.

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation-seq, RNA-seq, and high-throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element-binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40-mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.

Enhancement pattern of the pancreatic parenchyma predicts postpancreatectomy acute pancreatitis after pancreaticoduodenectomy.

OBJECTIVES: To assess the association between the enhancement pattern of the pancreatic parenchyma on preoperative multiphasic contrast-enhanced computed tomography (CECT) and the occurrence of postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD). METHODS: A total of 513 patients who underwent PD were retrospective enrolled. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases in the pancreatic parenchyma were measured on preoperative multiphasic CECT. The enhancement pattern was quantized by the CT attenuation value ratios in each phase. Receiver operating characteristic (ROC) curve analyses were computed to evaluate predictive performance. Regression analyses were used to identify independent risk factors for PPAP. RESULTS: PPAP developed in 102 patients (19.9%) and was associated with increased morbidity and a worse postoperative course. The A/P ratio, P/L ratio, and A/L ratio were significantly higher in the PPAP group. On the ROC analysis, the A/L ratio and A/P ratio both performed well in predicting PPAP (A/L: AUC = 0.7579; A/P: AUC = 0.7497). On multivariate analyses, the A/L ratio > 1.29 (OR 4.30 95% CI: 2.62-7.06, p < 0.001) and A/P ratio > 1.13 (OR 5.02 95% CI: 2.98-8.45, p < 0.001) were both independent risk factors of PPAP in each model. CONCLUSIONS: The enhancement pattern of the pancreatic parenchyma on multiphasic preoperative CECT is a good predictor of the occurrence of PPAP after PD, which could help clinicians identify high-risk patients or enable selective enhance recovery protocols. CLINICAL RELEVANCE STATEMENT: Preoperative identification of patients at high risk for postpancreatectomy acute pancreatitis by enhancement patterns of the pancreatic parenchyma allows surgeons to tailor their perioperative management and take precautions. KEY POINTS: PPAP is associated with increased risk of postoperative complications and a worse postoperative course. A rapid-decrease enhancement pattern of the pancreatic parenchyma is related to the occurrence of PPAP. The A/L and A/P ratios were both independent risk factors of PPAP in each multivariate model.

ATF3-induced activation of NF-κB pathway results in acquired PARP inhibitor resistance in pancreatic adenocarcinoma.

PURPOSE: Olaparib, an inhibitor of poly-(adenosine diphosphate-ribose) polymerase (PARP), has been shown to have anticancer benefits in patients with pancreatic cancer who have a germline mutation in BRCA1/2. However, resistance acquired on long-term exposure to olaparib significantly impedes clinical efficacy. METHODS: In this study, the chromatin accessibility and differentially expressed transcripts of parental and olaparib-resistant pancreatic cancer cell lines were assessed using the Assay for Transposase Accessible Chromatin with sequencing (ATAC-seq) and mRNA-seq. Detection of downstream genes regulated by transcription factors using ChIP (Chromatin immunoprecipitation assay). RESULTS: According to pathway enrichment analysis, differentially expressed genes in olaparib-resistant cells were remarkably enriched in the NF-κB signaling pathway. With ATAC-seq, we identified chromatin regions with higher accessibility in olaparib-resistant cells and predicted a series of important transcription factors. Among them, activating transcription factor 3 (ATF3) was significantly highly expressed. Functional experiments verified that inhibition of ATF3 suppressed the NF-κB pathway significantly and restored olaparib sensitivity in olaparib-resistant cells. CONCLUSION: Experiments in vitro and in vivo indicate ATF3 enhances olaparib resistance through the NF-κB signaling pathway, suggesting that ATF3 could be employed as an olaparib sensitivity and prognostic indicator in patients with pancreatic cancer.

Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement-A retrospective study.

BACKGROUND: The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. METHOD: All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. RESULTS: The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. CONCLUSION: This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.

Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10.

Long non-coding RNAs are considered to be key regulatory factors of oncogenesis and tumor progression. It is reported that LINC00460 plays the role of oncogene in some tumors. However, LINC00460's role and mechanism of action in pancreatic cancer have not yet been fully elucidated. We identified LINC00460 by analyzing data from the Gene Expression Omnibus database. The role of LINC00460 in proliferation and metastasis was examined using CCK8, colony formation, wound healing, and transwell assays. The potential mechanisms of LINC00460 in regulating mRNA levels were elucidated by RNA pull-down, RNA immunoprecipitation, Chromatin immunoprecipitation, Co-immunoprecipitation, and Immunofluorescence assays. The results showed that LINC00460 was upregulated in pancreatic cancer cells and tissues. Highly expressed LINC00460 is significantly related to short survival of pancreatic cancer patients. Inhibition of LINC00460 attenuated pancreatic cancer cell proliferation and metastasis, whereas its overexpression reversed this effect. Mechanically, LINC00460 is induced by hypoxia, through binding of the hypoxia-inducible factor 1-α in the promoter region of LINC00460. Furthermore, LINC00460 functioned as an miR-4689 sponge to regulate the downstream target gene UBE2V1, enhancing the stability of mutant p53 in pancreatic cancer cells. LINC00460 also further promotes pancreatic cancer development by sequestering USP10, a cytoplasmic ubiquitin-specific protease that deubiquitinates p53 and enhances its stability. Collectively, our study demonstrated that LINC00460 is a hypoxia-induced lncRNA that plays the role of oncogene in pancreatic cancer by modulating the miR-4689/UBE2V1 axis, sequestering USP10, and ultimately enhancing the stability of mutant p53.

Comprehensive machine learning-generated classifier identifies pro-metastatic characteristics and predicts individual treatment in pancreatic cancer: A multicenter cohort study based on super-enhancer profiling.

Rationale: Accumulating evidence illustrated that the reprogramming of the super-enhancers (SEs) landscape could promote the acquisition of metastatic features in pancreatic cancer (PC). Given the anatomy-based TNM staging is limited by the heterogeneous clinical outcomes in treatment, it is of great clinical significance to tailor individual stratification and to develop alternative therapeutic strategies for metastatic PC patients based on SEs. Methods: In our study, ChIP-Seq analysis for H3K27ac was performed in primary pancreatic tumors (PTs) and hepatic metastases (HMs). Bootstrapping and univariate Cox analysis were implemented to screen prognostic HM-acquired, SE-associated genes (HM-SE genes). Then, based on 1705 PC patients from 14 multicenter cohorts, 188 machine-learning (ML) algorithm integrations were utilized to develop a comprehensive super-enhancer-related metastatic (SEMet) classifier. Results: We established a novel SEMet classifier based on 38 prognostic HM-SE genes. Compared to other clinical traits and 33 published signatures, the SEMet classifier possessed robust and powerful performance in predicting prognosis. In addition, patients in the SEMetlow subgroup owned dismal survival rates, more frequent genomic alterations, and more activated cancer immunity cycle as well as better benefits in immunotherapy. Remarkably, there existed a tight correlation between the SEMetlow subgroup and metastatic phenotypes of PC. Among 18 SEMet genes, we demonstrated that E2F7 may promote PC metastasis through the upregulation of TGM2 and DKK1. Finally, after in silico screening of potential compounds targeted SEMet classifier, results revealed that flumethasone could enhance the sensitivity of metastatic PC to routine gemcitabine chemotherapy. Conclusion: Overall, our study provided new insights into personalized treatment approaches in the clinical management of metastatic PC patients.

A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis.

PURPOSE: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. METHODS: Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. RESULTS: A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. CONCLUSION: With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment.

A deep-learning radiomics-based lymph node metastasis predictive model for pancreatic cancer: a diagnostic study.

OBJECTIVES: Preoperative lymph node (LN) status is essential in formulating the treatment strategy among pancreatic cancer patients. However, it is still challenging to evaluate the preoperative LN status precisely now. METHODS: A multivariate model was established based on the multiview-guided two-stream convolution network (MTCN) radiomics algorithms, which focused on primary tumor and peri-tumor features. Regarding discriminative ability, survival fitting, and model accuracy, different models were compared. RESULTS: Three hundred and sixty-three pancreatic cancer patients were divided in to train and test cohorts by 7:3. The modified MTCN (MTCN+) model was established based on age, CA125, MTCN scores, and radiologist judgement. The MTCN+ model outperformed the MTCN model and the artificial model in discriminative ability and model accuracy. [Train cohort area under curve (AUC): 0.823 vs. 0.793 vs. 0.592; train cohort accuracy (ACC): 76.1 vs. 74.4 vs. 56.7%; test cohort AUC: 0.815 vs. 0.749 vs. 0.640; test cohort ACC: 76.1 vs. 70.6 vs. 63.3%; external validation AUC: 0.854 vs. 0.792 vs. 0.542; external validation ACC: 71.4 vs. 67.9 vs. 53.5%]. The survivorship curves fitted well between actual LN status and predicted LN status regarding disease free survival and overall survival. Nevertheless, the MTCN+ model performed poorly in assessing the LN metastatic burden among the LN positive population. Notably, among the patients with small primary tumors, the MTCN+ model performed steadily as well (AUC: 0.823, ACC: 79.5%). CONCLUSIONS: A novel MTCN+ preoperative LN status predictive model was established and outperformed the artificial judgement and deep-learning radiomics judgement. Around 40% misdiagnosed patients judged by radiologists could be corrected. And the model could help precisely predict the survival prognosis.

The value of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance whole-body scans and local enhancement scans in the preoperative staging and resectability assessment of pancreatic adenocarcinoma.

Background: In addition to contrast-enhanced multiphase computed tomography (CT) and magnetic resonance imaging (MRI), integrated positron emission tomography (PET)/magnetic resonance (MR) is increasingly being used for the preoperative evaluation of pancreatic cancer. The purpose of this study was to explore the value of hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MR imaging in preoperative assessment and treatment decision-making. Methods: A retrospective data collection (of imaging, clinical, and pathological information) was conducted on patients who underwent 18F-FDG PET/MR with clinically diagnosed or suspected pancreatic cancer from March 2018 to March 2022 in Ruijin Hospital. The data of 76 patients were initially included, with 1 of the 76 patients eventually being excluded due to a misdiagnosis of inflammatory disease. Of the 75 patients, 38 underwent pancreatic tumor resection and 10 underwent laparoscopic exploration. The accuracy of 18F-FDG PET/MR for pancreatic cancer staging and the assessment of pancreatic resectability was evaluated based on pathological results, intraoperative findings, and documented final clinical stages of illness. The adjustments to patient treatment plans were also analyzed before and after 18F-FDG PET/MR examination. Results: The accuracy of clinical tumor node metastasis (TNM) staging of pancreatic cancer by 18F-FDG PET/MR was 73.3% (55/75). The area under the curve (AUC) of 18F-FDG PET/MR for diagnosing the advanced stage (III-IV) versus the nonadvanced stage (I-II) of disease was 0.922 [95% confidence interval (CI): 0.852-0.993]. The treatment regimen of 20.0% (15/75) of patients was impacted. The accuracy of the evaluation of the resectability of pancreatic cancer with 18F-FDG PET/MR was 91.9% (34/37). With the surgical and pathological results being used as a reference, the overall accuracy of preoperative 18F-FDG PET/MR for T staging was 62.2%, and the AUC for diagnosing T4 versus T1-3 was 0.872 (95% CI: 0.660-1.000). Conclusions: 18F-FDG PET/MR performs well in diagnosing advanced pancreatic cancer and thus may impact the treatment decisions for a considerable number of patients. 18F-FDG PET/MR has a high level of accuracy in evaluating the resectability of pancreatic cancer before surgery.

A dual-transformation with contrastive learning framework for lymph node metastasis prediction in pancreatic cancer.

Pancreatic cancer is a malignant tumor, and its high recurrence rate after surgery is related to the lymph node metastasis status. In clinical practice, a preoperative imaging prediction method is necessary for prognosis assessment and treatment decision; however, there are two major challenges: insufficient data and difficulty in discriminative feature extraction. This paper proposed a deep learning model to predict lymph node metastasis in pancreatic cancer using multiphase CT, where a dual-transformation with contrastive learning framework is developed to overcome the challenges in fine-grained prediction with small sample sizes. Specifically, we designed a novel dynamic surface projection method to transform 3D data into 2D images for effectively using the 3D information, preserving the spatial correlation of the original texture information and reducing computational resources. Then, this dynamic surface projection was combined with the spiral transformation to establish a dual-transformation method for enhancing the diversity and complementarity of the dataset. A dual-transformation-based data augmentation method was also developed to produce numerous 2D-transformed images to alleviate the effect of insufficient samples. Finally, the dual-transformation-guided contrastive learning scheme based on intra-space-transformation consistency and inter-class specificity was designed to mine additional supervised information, thereby extracting more discriminative features. Extensive experiments have shown the promising performance of the proposed model for predicting lymph node metastasis in pancreatic cancer. Our dual-transformation with contrastive learning scheme was further confirmed on an external public dataset, representing a potential paradigm for the fine-grained classification of oncological images with small sample sizes. The code will be released at https://github.com/SJTUBME-QianLab/Dual-transformation.

The Impact of Additional Para-aortic Dissection During Pancreaticoduodenectomy for Resectable Pancreatic Cancer.

BACKGROUND: The short-term outcome and long-term survival of pancreaticoduodenectomy with additional para-aortic dissection (PAD) for patients with resectable pancreatic cancer remain obscure. PATIENTS AND METHODS: Consecutive patients who underwent radical pancreaticoduodenectomy for resectable pancreatic cancer in a single high-volume center during a 7-year period were included retrospectively. Both short- and long-term effects of PAD were compared between the PAD group and the no PAD group. Then, the PAD group was divided into the non-metastatic para-aortic lymph node (PALN-) group and the metastatic PALN (PALN+) group to further analyze the prognosis of PALN+. RESULTS: Of the 909 included patients, 280 (30.8%) underwent PAD during pancreaticoduodenectomy. The PAD group had a higher rate of intra-abdominal infection compared with the no PAD group (28.6% vs. 20.7%, P = 0.009) but no differences were found in the incidence of other complications. The overall survival (OS) and recurrence-free survival (RFS) were also comparable between the two groups. Subgroup analysis showed that patients with PALN+ had a worse OS than patients in the PALN- group (median of 14 vs. 20 months, P = 0.048). Multivariate Cox regression analysis further revealed that PALN+ was an independent adverse predictor of OS (hazard ratio: 1.70, P = 0.007). CONCLUSIONS: This study suggests that the addition of PAD during pancreaticoduodenectomy does not improve the prognosis of patients with resectable pancreatic cancer and may lead to an increased risk of infection. However, the accurate preoperative assessment and appropriate treatment strategy for patients with PALN+ need further investigation due to the poor prognosis.

Postpancreatectomy Acute Pancreatitis After Pancreaticoduodenectomy: A Distinct Clinical Entity.

OBJECTIVE: This study aimed to characterize postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD) in a high-volume center. BACKGROUND: The International Study Group for Pancreatic Surgery (ISGPS) has recently proposed a new definition and grading scale of PPAP, but specific studies are lacking. METHODS: Patients who underwent PD from 2020 to 2021 were retrospectively reviewed. PPAP was defined based on the International Study Group for Pancreatic Surgery definition: sustained elevation of serum amylase levels for least the first 48 hours postoperatively and radiologic alterations consistent with PPAP. RESULTS: Among a total of 716 patients who were finally analyzed, PPAP occurred in 152 (21.2%) patients. Patients with PPAP were associated with significantly higher incidences of postoperative pancreatic fistula (POPF) (40.8% vs 11.7%, P <0.001), major complications (13.8% vs 6.6%, P =0.004), and biliary leak (11.8% vs 4.6%, P =0.001). Among them, 8 patients developed grade C PPAP leading to organ failure, reoperation, or death. Patients developing PPAP alone also demonstrated a statistically significantly increased rate of major complications than those without PPAP or POPF. In contrast, no differences were found in postoperative outcomes in patients with POPF in terms of whether they were associated with PPAP. CONCLUSION: PPAP is a distinct complication after PD with distinctive clinical outcomes. A part of PPAP presents as an inflammatory process in the early postoperative period but sometimes could lead to necrotizing pancreatitis or other severe clinical scenarios, and another part of PPAP would lead to anastomotic failure that accounts for a great proportion of POPF occurrence.

Impact of the transection plan on postoperative pancreatic fistulas occurring after robot-assisted distal pancreatectomy for nonmalignant pancreatic neoplasms.

OBJECTIVES: Postoperative pancreatic fistula (POPF) is the main complication of distal pancreatectomy (DP) and affects the prognosis of patients. The impact of several clinical factors mentioned in recent studies on POPF remains controversial. This study aimed to investigate the impact of a remnant pancreas and other perioperative factors on POPFs occurring after robot-assisted distal pancreatectomy (RDP) for nonmalignant pancreatic neoplasms. METHODS: A total of 197 patients who received robot-assisted distal pancreatectomy (RDP) for nonmalignant pancreatic neoplasms at the Pancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2018 to December 2020 were included in this retrospective study. According to the intraoperative transection plan, patients were divided into an RDP body group and an RDP tail group. Clinical and pathological features and perioperative factors affecting POPF were analyzed and compared between the two groups. RESULTS: The results showed that a transection plan involving the tail of the pancreas (OR = 2.133, 95% CI 1.109-4.103, p = 0.023) and spleen preservation (OR = 2.588, 95% CI 1.435-4.665, p = 0.001) independently increased the incidence of POPF in patients with nonmalignant pancreatic neoplasms treated by RDP. A transection plan involving the tail of the pancreas was also an independent risk factor (OR = 3.464, 95% CI 1.270-9.450, p = 0.015) for grade B/C POPF. Length of remnant pancreas > 6.23 cm was an independent risk factor for POPF (OR = 3.116, 95% CI 1.364-7.121, p = 0.007). Length of remnant pancreas > 9.82 cm was an independent risk factor for grade B/C POPF (OR = 3.340, 95% CI 1.386-8.051, p = 0.007). CONCLUSION: This retrospective study suggests that a transection plan involving the tail of the pancreas is an independent risk factor for POPF in patients with nonmalignant neoplasms treated by RDP. We also propose that the postoperative length of the remnant pancreas evaluated by computed tomography scans can be used to identify patients with a high risk of POPF in order to optimize the individualized strategy.

Long-term outcomes of standard versus extended lymphadenectomy in pancreatoduodenectomy for pancreatic ductal adenocarcinoma: A Chinese multi-center prospective randomized controlled trial.

INTRODUCTION: The value of extended lymphadenectomy in pancreatoduodenectomy (PD) has been discussed by five randomized controlled studies. However, the limitations in the studies made their conclusions not sufficiently reliable. OBJECTIVES: This multi-center randomized controlled study was designed to clarify the efficacy of extended lymphadenectomy in PD for pancreatic ductal adenocarcinoma (PDAC). METHODS: From December 2016 to October 2018, 170 consecutive patients undergoing PD were enrolled and randomized to standard or extended lymphadenectomy for the treatment of PDAC from three high-volume institutions in China. Demographic, pathological characteristics and survival data of these patients were collected and analyzed. No neoadjuvant treatment was performed. The primary endpoint was the 3-year overall survival. RESULTS: For all patients, the 3-year survival rate was 25.88 %. There was no between-group difference in 3-year survival rate (27.16 % vs 24.72 % p = 0.717). The median survival time for the standard group was 18 months, while for the extended group it was 15 months. The demographic and pathological characteristics were similar between groups. More positive lymph nodes could be found in the extended group (2.34 ± 3.46 vs 1.41 ± 2.12, p = 0.035), which led to nodule stage migration. All patients received chemotherapy. But patients in extended group were more likely to fail in completion of all-cycles chemotherapy before recurrence (31.46 % vs 17.28 %, p = 0.032). Incomplete chemotherapy before recurrence, higher N status and abnormal CA125 were independent risk factors for 1-year survival (p < 0.001, 95 % CI 0.076-0.368; p = 0.017, 95 % CI 1.113-3.021; p = 0.021, 95 % CI 1.136-4.960, respectively), which was higher in the standard group (75.31 % vs 58.43 %, p = 0.020). CONCLUSION: The extended lymphadenectomy in PD did not improve the long-term survival in patients with PDAC. Patients with extended lymphadenectomy had a worse 1-year overall survival. However, the nodule stage migration facilitated by the extended lymphadenectomy contributed to the precise tumor staging.

TNFAIP3 Mediated by Novel Nano Composite Adsorbent on Tumor Necrosis Factor-α in Rats with Lumbar Disc Herniation by Inhibiting NF-κB Pathway.

Mobile phones and computers have been widely used in the work of people. The incidence rate of lumbar disc herniation(LDH) has gradually increased and the trend toward younger age has been increasing. According to the epidemiological survey, about half of people will experience lumbar pain in their life and the resulting huge social and economic burden. It has important clinical significance for the treatment of lumbar disc herniation of TNFaIP3 mediated by a new nanocomposite adsorbent on tumor necrosis factor(TNF)- in rats with LDH by inhibiting the  pathway. This paper mainly studies the mechanism and efficacy of TNFaIP3 mediated by a new nanocomposite adsorbent on TNF- in rats with LDH by inhibiting the  pathway. Eight groups of human nucleus pulposus cells were randomly divided into four groups: high inhibition group, medium inhibition group, low inhibition group and no inhibition group. After interfering with human nucleus pulposus cells by inhibiting the  pathway, the cells were allowed to stand for 24 hours to extract and detect TNF-, p-p65, P50, IKB and IKK in the  signaling pathway to explore the mechanism of inhibiting  pathway on TNF- in rats with LDH. The experimental results showed that after 24 hours of intervention, compared with the non-inhibition group, the expression of TNF in the low inhibition group, medium inhibition group and high inhibition group decreased relatively, and with the increase of inhibition degree, the expression of TNF in each group decreased more obviously, such as the expression of TNF in non-inhibition group was 1.48, the expression of TNF in low inhibition group was 1.31, the expression of TNF in medium inhibition group was 0.74, and the expression of TNF in high inhibition group was 0.58. The expression of P50 was 1.86 in non-inhibition, 1.47 in low inhibition, 1.32 in medium inhibition and 1.13 in high inhibition.