Pancreas最新文献

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high metastatic ability, poor prognosis, and resistant to treatment. Tumor microenvironment plays a major role in the complexity of PDAC.

Objective of the study: The aim of the study was to examine the role of P21 activated kinase-1 (PAK1) in the sustenance of tumor microenvironment to enable tumor growth and progression.

Methodology: The effect of PAK1 in the tumor microenvironment was analyzed using a novel co-culture method involving pancreatic cancer cells and pancreatic stellate cells. The 2 cell types were grown in both direct and indirect cell culture models to facilitate the juxtracrine signaling and establish a secretome network. The established network was studied using the transcriptome sequencing of PAK1-modulated MIA PaCa-2 cells co-cultured with stellate cells.

Results: The results showed that PAK1 influenced cells have increased interferon pathway when compared to PAK1 depleted cells. The levels of chemokine CCL3 was altered in PAK1-modulated cells as evidenced by the bioinformatic, QPCR, and ELISA analysis. The pathway and interactome analysis showed that CCL3 promotes interferon activation and myofibroblast differentiation in pancreatic cancer microenvironment. These results might help in identifying the PAK1 induced metastatic network in pancreatic cancer. Further investigation will provide adequate evidence of CCL3 and PAK1 in pancreatic carcinogenesis and metastasis.

Conclusions: The present study provides an understanding of tumor microenvironment and involvement of inflammatory cytokines in a juxtacrine mechanism to aggravate and accelerate pancreatic adenocarcinoma.

Objectives: A significant proportion of patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) are anemic at the time of resection. In these patients, blood transfusions are omitted because of their potential negative impact on oncological outcomes. The present study aimed to determine the prognostic value of preoperative anemia in resected PDAC patients, irrespective of blood transfusion status.

Materials and methods: This retrospective 2-center cohort study included patients who underwent resection for PDAC between 2013 and 2022. The prognostic role of preoperative anemia was investigated using Cox proportional-hazard regression analysis. A subgroup analysis excluded PDAC patients who received a perioperative blood transfusion.

Results: Among 280 included PDAC patients, 110 (39%) were found to have preoperative anemia. Preoperative anemia was associated with increased use of blood transfusions, with 44 patients (16%) requiring transfusion perioperatively. In the whole cohort, preoperative anemia was an independent predictor of lower disease-free survival (hazard ratio [HR] = 1.518; 95% confidence interval [CI] = 1.103-2.090, P  = 0.011), but not overall survival. However, when patients who received a perioperative blood transfusion were excluded, preoperative anemia was independently associated with both lower disease-free survival (HR = 1.636; 95% CI = 1.113-2.404, P  = 0.012) and overall survival (HR = 1.484; 95% CI = 1.036-2.127, P  = 0.031).

Conclusions: Preoperative anemia was identified as an independent risk factor for inferior oncological survival after resection for PDAC. These results support the need for increased awareness regarding the potential adverse effects of preoperative anemia on oncological outcomes in PDAC.

Objectives: There are numerous studies on predicting relapse of autoimmune pancreatitis (AIP). Serum autotaxin (ATX) was recently found to associate with AIP relapse. This study examined the changes in serum IgG4 and ATX levels for predicting relapse in AIP patients.

Materials and methods: Patients with AIP who had received initial steroid therapy were retrospectively enrolled. Serum IgG4 and ATX levels were measured before and after treatment. The rates of decrease (Δ) in serum marker levels were calculated by dividing the difference between before and after steroid therapy by the number of days between them.

Results: The 37 AIP patients analyzed included 26 nonrelapse and 11 relapse patients. The median Δ of serum IgG4 was 5.19 [interquartile range (IQR): 2.65-14.49] in the nonrelapse group and statistically comparable to the 3.07 (IQR: 1.79-4.43) in the relapse group ( P =0.12). The median Δ of serum ATX was 1.32×10 -3 (IQR: 0.23×10 -3 -2.45×10 -3 ) in the nonrelapse group and 0.58×10 -3 (IQR: -1.34×10 -3 -0.91×10 -3 ) in the relapse group, which was a significant difference ( P <0.01). Positive predictive values for relapse was 86.5% when the Δ of IgG4 and the Δ of ATX were combined.

Conclusions: The combination of IgG4 and ATX decrease rates may help predict relapse in AIP patients after steroid therapy.

Objective: Pancreatic necrosis is a catastrophic complication of acute pancreatitis and is associated with increased morbidity and mortality. While there is no objective means to predict pancreatic necrosis, recent studies have identified serum phosphate levels as a contributor to the disease process, with worse outcomes noted in patients with low serum phosphates. We aimed to determine if there was a relationship between low serum phosphate levels and the risk of developing pancreatic necrosis in patients with acute alcoholic pancreatitis (AAP).

Methods: Health care records from patients admitted between January 2017 and December 2022 for acute alcoholic pancreatitis were retrospectively reviewed. These patients were categorized based on their phosphate levels within 48 hours of admission: normal phosphate levels (2.8-4.5 mg/dL) and hypophosphatemia (<2.8 mg/dL). Imaging findings from hospital stays were examined to identify cases of pancreatic necrosis. These cases were then compared across patients with normal and low phosphate levels.

Results: Among the 207 patients admitted for acute alcoholic pancreatitis, 67 met the inclusion and exclusion criteria. Of these, 37 patients exhibited serum phosphate levels below 2.8 mg/dL, while 30 maintained levels between 2.8 and 4.5 mg/dL within the first 48 hours of admission. Of the patients in the hypophosphatemia group, 27.02% were noted to develop pancreatic necrosis during hospital stay compared to only 6.66% in the normal phosphate group ( P value: 0.029). In addition, those who developed necrosis had an overall lower mean phosphate level of 2.13 mg/dL compared to the mean phosphate level of 2.60 mg/dL ( P value: 0.0521) in patients without necrosis. The median duration of hospital stay ( P value: 0.65) and rate of intensive care unit (ICU) admission ( P value: 0.41) were similar in both groups.

Conclusions: Early hypophosphatemia during admission for AAP was associated with an increased risk of developing pancreatic necrosis; however, it may not affect the overall length of hospital stay or rate of ICU admission.

Background: Acute pancreatitis (AP) is the most common disease in emergency and intensive care units; early mortality predictions and intervention are crucial for improving patient prognosis. We investigated the association of serum phosphate with mortality among AP patients using a large public database.

Methods: This was a retrospective study. All AP patients in the MIMIC-IV database were included. Based on the tertiles of serum phosphate, all AP patients were divided into 3 groups. Two generalized additive models were performed to explore the association of serum phosphate with in-hospital and 30-day mortality. Kaplan-Meier analysis was introduced for survival probability.

Results: A total of 1088 AP patients admitted to the ICU were included. The mortalities of in-hospital (n=137) and 30-day (n=118) were 12.59% and 10.85%, respectively. The median levels of serum phosphate in the survivor and the non-survivor groups were 3.20 and 3.90 mg/dL, respectively (P<0.001). After adjusting for all potential confounders, with 1 mg/dL increment in serum phosphate, the risk of in-hospital and 30-day mortality increased by 20% (HR=1.20, 95% CI: 1.00-1.44, P=0.0443) and 25% (HR=1.25, 95% CI: 1.03-1.52, P=0.0214), respectively. The areas under the ROC curve (AUC) of serum phosphate for predicting in-hospital and 30-day mortality were 0.650 (95% CI: 0.599-0.701) and 0.659 (95% CI: 0.605-0.714), respectively. The cutoff values of serum phosphate were 3.65 and 4.35 mg/dL, respectively.

Conclusions: A linear positive relationship was found between serum phosphate and in-hospital and 30-day mortality in AP. Serum phosphate was associated with in-hospital and 30-day mortality in AP. Our results could be used for screening out those AP patients with a higher risk of worse outcomes.

Background and objectives: Accurate survival prediction for pancreatic ductal adenocarcinoma (PDAC) is crucial for personalized treatment strategies. This study aims to construct a novel pathomics indicator using hematoxylin and eosin-stained whole slide images and deep learning to enhance PDAC prognosis prediction.

Methods: A retrospective, 2-center study analyzed 864 PDAC patients diagnosed between January 2015 and March 2022. Using weakly supervised and multiple instance learning, pathologic features predicting 2-year survival were extracted. Pathomics features, including probability histograms and TF-IDF, were selected through random survival forests. Survival analysis was conducted using Kaplan-Meier curves, log-rank tests, and Cox regression, with AUROC and C-index used to assess model discrimination.

Results: The study cohort comprised 489 patients for training, 211 for validation, and 164 in the neoadjuvant therapy (NAT) group. A pathomics score was developed using 7 features, dividing patients into high-risk and low-risk groups based on the median score of 131.11. Significant survival differences were observed between groups (P<0.0001). The pathomics score was a robust independent prognostic factor [Training: hazard ratio (HR)=3.90; Validation: HR=3.49; NAT: HR=4.82; all P<0.001]. Subgroup analyses revealed higher survival rates for early-stage low-risk patients and NAT responders compared to high-risk counterparts (both P<0.05 and P<0.0001). The pathomics model surpassed clinical models in predicting 1-, 2-, and 3-year survival.

Conclusions: The pathomics score serves as a cost-effective and precise prognostic tool, functioning as an independent prognostic indicator that enables precise stratification and enhances the prediction of prognosis when combined with traditional pathologic features. This advancement has the potential to significantly impact PDAC treatment planning and improve patient outcomes.