Pancreas最新文献

Objective: This study aims to assess the effectiveness of coupled plasma filtration and adsorption (CPFA) in patients with SAP through its effect on inflammatory mediators and sublingual circulating blood volume. The hypothesis put to test is that CPFA can achieve a satisfactory reduction in inflammatory mediators and enhance sublingual microcirculation in SAP with a very good clinical outcome.

Methods: A cohort of 112 SAP patients admitted to the ICU of our institution between January 2018 and December 2022 was consecutively recruited. Participants were randomized to the CPFA or the control group (standard treatment) using a random number table for assignment. Posttreatment alterations in inflammatory mediators and sublingual microcirculation were analyzed and compared.

Results: Following treatment, the study group showed significantly reduced levels of IL-1β, TNF-α, and IL-6 versus the control group. In addition, the study group witnessed lower serum and urinary amylase levels and APACHE II and SOFA scores. Parameters related to sublingual microcirculation, including total vessel density (TVDs), small vessel perfusion ratio (PPVs), perfusion small vessel density (PVDs), and microvascular flow index (MFIs), were significantly improved in the study group. Moreover, the study group observed lower rates of systemic inflammatory response syndrome (SIRS) and 30-day mortality versus the control group.

Conclusions: The application of CPFA in SAP patients effectively eliminates inflammatory mediators and enhances microcirculation, leading to improved clinical outcomes and reduced mortality rates.

Objective: This study aimed to explore the function of TNF receptor superfamily member 9 (TNFRSF9) in pancreatic ductal adenocarcinoma (PDA) by investigating its expression levels and functional implications in PDA cells.

Materials and methods: TNFRSF9 expression was evaluated in patients with PDA, and TNFRSF9 levels were manipulated in PDA cells to assess its effects on cell proliferation, migration, and apoptosis. The downstream target gene PAX6 was also examined. In vivo, studies in nude mice were performed to analyze the impact of TNFRSF9 overexpression on tumor growth.

Results: Analysis revealed decreased TNFRSF9 expression in PDA tissues. Ectopic TNFRSF9 expression in PDA cells suppressed cell proliferation and migration and induced apoptosis, while TNFRSF9 knockout showed opposing effects. PAX6 was identified as a downstream target of TNFRSF9. TNFRSF9 overexpression in nude mice led to reduced tumor growth.

Conclusion: The study suggests that TNFRSF9 may hold promise as a therapeutic target in PDA management, given its potential to inhibit tumor growth and modulate cell behavior.

Background: Pancreas transplantation (PTx) is a definitive therapy for patients with type 1 diabetes and advanced chronic kidney disease. Abdominal aortic calcification (AAC) is often observed in patients waiting for PTx and progresses according to the waiting period, but the impact of AAC on long-term outcomes remains unclear. In this study, we aimed to elucidate the impact of AAC on long-term outcomes.

Methods: We reviewed 65 consecutive PTx cases at our institution between April 2000 and November 2022 and enrolled 50 patients with simultaneous pancreas-kidney transplantation (SPK). AAC was assessed as AAC score by the Agatston method using multidetector computed tomography.

Results: Receiver operating characteristic curves were used to determine the cutoff value of the AAC score for death-uncensored pancreas graft survival; the area under the curve was 0.711 ( P =0.029). After dividing the patients into 2 groups according to the AAC cutoff, the dialysis period was significantly longer in the high AAC score group than in the low AAC score group ( P =0.001). Death-uncensored pancreas graft survival and patient survival after SPK were significantly lower in the high AAC score group than in the low AAC score group ( P =0.001, 0.001, respectively). In a Cox proportional hazards regression model, a high AAC score was independently associated with death-uncensored pancreas graft loss ( P =0.002).

Conclusions: AAC is associated with death-uncensored pancreas graft survival in patients undergoing SPK. Evaluation of AAC could be useful for predicting post-PTx prognosis.

Objectives: To elucidate the role of N-acetyltransferase 10 (NAT10) in pancreatic cancer (PC) progression and its epigenetic mechanisms, particularly in relation to metastasis.

Methods: TCGA and GTEx databases were used to analyze the expression and roles of NAT10 in pancreatic cancer. We constructed stable cell lines with NAT10 knockdown in PC cell lines, AsPC-1 and KPC. CCK-8, EdU assay, and colony formation assay were conducted to evaluate the capability of cell proliferation and clonogenesis in vitro. Meanwhile, a transwell assay was performed to assess the impact on invasion and metastasis abilities. The correlation between NAT10 and ZEB1 expression was verified by correlation analysis. The underlying mechanisms through which NAT10 regulates ZEB1 were confirmed by qPCR, western blot, RIP-qPCR, dot plot, and mRNA stability assay. Furthermore, the interplay among NAT10, ZEB1, and MT1-MMP was confirmed using similar experimental approaches. Rescue experiments involving ZEB1 overexpression further verified the role of NAT10/ZEB1/MT1-MMP axis in PC metastasis. In addition, the NAT10 inhibitor Remodelin was employed in a nude orthotopic PC model to investigate its effects on metastasis in vivo.

Results: NAT10 was found to be upregulated in PC and was significantly associated with poor prognosis. After NAT10 knockdown, the ability of proliferation and metastasis of AsPC-1 and KPC was remarkably impaired, the degree of ac4C modification was decreased, and the mRNA stability of ZEB1 declined. Correlation analysis indicated a positive correlation among NAT10, ZEB1, and MT1-MMP, and the results of qPCR and western blot also verified this conclusion. Moreover, ZEB1 overexpression could significantly reverse the inhibition of migration and invasion induced by NAT10 depletion in AsPC-1. NAT10 inhibitor Remodelin treatment could reduce the degree of peritoneal and liver metastases in vivo.

Conclusions: Our study highlights the pivotal functions of NAT10 in the progression of PC and reveals the underlying epigenetic mechanism that NAT10 promotes metastasis via ZEB1/MT1-MMP axis.

Objectives: This study investigated the relationship between serum 25-Hydroxyvitamin D [25(OH)D] levels, vitamin D receptor (VDR) gene polymorphisms, and the prognosis of acute pancreatitis (AP).

Methods: This prospective observation study included patients with AP admitted to the Jinling Hospital between January 2018 and December 2019. Clinical information, laboratory tests, and single-nucleotide polymorphisms (SNPs) of the VDR gene were collected.

Results: A total of 508 AP patients were included, with a mean age of 44.81 ± 13.80 years. Among them, 158 (31.10%) cases developed sepsis, 211 (41.54%) cases had serious AP, and 47 (9.25%) patients died before discharge. The multivariate regression analysis showed that VD deficiency was an independent risk factor for the occurrence of sepsis (OR=3.768, 95% CI: 2.368-5.997, P <0.001), progression of AP patients to serious AP (OR=4.297, 95% CI: 2.806-6.582, P <0.001), and in-hospital mortality in AP patients (OR=2.406, 95% CI: 1.162-4.984, P =0.018). SNPs of VDR associated with sepsis, serious AP, or in-hospital death were identified, including rs12721375, rs2853559, rs11168287, rs2853559, and rs11168283 (all P <0.05). The Generalized Multifactor Dimensionality Reduction model analysis revealed that a 4-order model (rs11168283, rs11168287, rs2853559, and 25(OH)D) was the best model for predicting death ( P <0.01).

Conclusions: VD deficiency and VDR genetic polymorphisms are associated with AP prognosis in Chinese Han patients with AP. VDR genetic polymorphism may influence the outcomes of AP patients by affecting the levels of inflammatory cytokines.

Objective: Managing painful chronic pancreatitis (CP) often involves invasive treatments, but success rates are variable. We aimed to describe the pain assessment tools used to measure the efficacy of endotherapy and surgery for painful CP and perform a meta-analysis of outcomes.

Design: PubMed, Embase, and Scopus databases were searched for published studies through April 1, 2023. Full papers in English that assessed pain outcomes among adults with painful CP undergoing invasive interventions were included.

Results: There were 413 out of 1,282 studies that underwent full-text review, and 279 studies were selected for the scoping review. Most commonly used pain assessment tools included symptom description (n=68 studies), numeric pain rating scales (NRS) or visual analog scales (VAS) (n=52), binary pain relief (yes or no) (n=27), and the pancreatitis-specific 4-item Izbicki score (n=28). In a meta-analysis of studies reporting preintervention and postintervention NRS or VAS (0-100), the mean decrease in pain after endoscopic intervention (n=9 studies) was 40.3 (95% CI: 27-53.6, P <0.001) and after surgical intervention (n=12 studies) it was 43.2 (95% CI: 31.5-54.9, P <0.001). A separate meta-analysis of studies reporting the preintervention and postintervention Izbicki score (n=5) showed similar findings. There was no difference in the change in pain scores between endotherapy and surgical cohorts in studies using NRS/VAS or Izbicki scores.

Conclusions: Pain outcomes were similar between endotherapy and surgery for painful CP based on the use of simple and highly variable pain assessment tools. Referral bias and sham effects need to be considered in future trials.

Introduction: Acute pancreatitis (AP) is a leading cause of gastrointestinal hospitalizations worldwide, with rising incidence, significant morbidity, and high healthcare costs. Pain, a hallmark symptom of AP, remains inadequately assessed, often relying on unidimensional scales such as visual analogue score, which fail to capture its multidimensional nature. Poorly managed acute pain negatively impacts clinical outcomes, prolongs recovery, and increases the risk of chronic pain syndromes. Comprehensive pain assessment tools specific to AP are lacking, highlighting the need for improved evaluation methods. The proposed study aims to develop and validate the Comprehensive Acute Pancreatitis Pain Outcome Set (CAPPOS) to address this evidence gap.

Methods: The CAPPOS initiative follows COMET and COSMIN guidelines. Three systematic reviews will identify pain domains and assessment methods in AP, acute abdominal pain, and postpancreatectomy pain. A consensus process, using a modified Delphi approach, will involve multidisciplinary experts and patients to confirm and define key domains. Measurement tools will be selected for each domain and refined through iterative feedback. Pilot testing with 50 patients will evaluate the feasibility, clarity, and responsiveness to change of the preliminary tool. Validation studies with 200 AP patients will assess structural, content, and criterion validity, reliability, and sensitivity to change, ensuring content validity and clinical utility.

Conclusion: CAPPOS will provide a validated, multidimensional core outcome set to optimize pain assessment in AP. It will also facilitate standardized reporting in clinical trials, advancing research and care for AP-related pain.

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly used as an option for the treatment of chronic and recurrent acute pancreatitis in selected patients. Studies have shown significant improvements in pain, quality of life, and opioid use postoperatively. However, in long-term follow-up, over half of the patients have episodes of abdominal pain following TPIAT. The aim of this work is to describe the array of causes of abdominal pain in this complex and growing patient population.

Methods: We conducted multidisciplinary discussions with experts at our institution and reviewed literature, where available, to identify and describe the diverse causes of abdominal pain following TPIAT.

Results: We identify 15 distinct causes of abdominal pain following TPIAT, describing their presentation, workup, and management.

Conclusion: As more patients undergo TPIAT, we must plan for and address the associated causes of abdominal pain that result from alterations in anatomy and physiology, both in the short and long term.

Objectives: CTRB2-del, a commonly occurring loss-of-function deletion variant in the CTRB2 gene encoding chymotrypsinogen B2 was shown to induce endoplasmic reticulum (ER) stress and increase risk for pancreatic cancer but not for chronic pancreatitis (CP). Since other digestive enzyme variants that cause misfolding and induce ER stress are strong risk factors for CP, the lack of association between CP and the CTRB2-del variant is surprising. The aim of the present study was to re-examine the biochemical and clinical characteristics of the CTRB2-del variant.

Methods: We performed experiments with AR42J cells transduced with adenoviral vectors and investigated disease association in Hungarian and German cohorts of CP cases.

Results: We found that the CTRB2-del protein was not secreted from AR42J cells but accumulated inside and induced significant ER stress. Curiously, epitope tagging CTRB2-del with a polyhistidine tail abolished its capacity to elicit ER stress even though the tagged construct remained defective in secretion and was retained intracellularly. Human genetic studies demonstrated similar carrier frequency of the CTRB2-del variant in CP cases and controls.

Conclusions: We replicated the ER-stress causing effect of the CTRB2-del variant and confirmed the lack of association with CP. The observations also revealed that epitope-tagging may alter the cellular effects of the CTRB2-del protein. The lack of association between ER stress and CP risk in carriers of the CTRB2-del variant raises the possibility that ER stress is a marker of digestive enzyme misfolding but does not drive CP onset and/or progression.

Background: Despite advancements in pancreatic surgery, new-onset diabetes mellitus following pancreatectomy (NODMP), persists, affecting patients' quality of life. Predicting NODMP before surgery could significantly enhance postoperative care.

Methods: This study included 220 patients who underwent pancreatoduodenectomy or distal pancreatectomy at Hirosaki University Hospital between January 2008 and December 2020. Patients with preoperative diabetes or <6 months' follow-up were excluded. The anticipated remnant pancreatic-to-splenic parenchyma computed tomography value ratio (remP/S ratio) was used to assess pancreatic fat content, with its cutoff determined using the receiving operator characteristic curve. Time to diabetes onset was analyzed using the Kaplan-Meier method. The risk factors for NODMP were identified using the Cox proportional hazards model.

Results: The mean diabetes-free period was 89.2 months over a median follow-up of 25.1 months. The incidence rates of NODMP at 1, 3, and 5 years after resection were 7.21%, 21.3%, and 28.0%, respectively. The significant risk factors for NODMP identified by univariate analysis were pancreatic cancer, preoperative HbA1c >5.7%, remP/S ratio <0.66, and remnant pancreatic volume <32.7 cm3. Multivariate analysis confirmed that a remP/S ratio <0.66 and preoperative HbA1c >5.7% were independent predictors of NODMP. The risk scoring system indicated that patients with both risk factors have a fivefold higher risk of developing NODMP within 2 years compared with those without either risk factor.

Conclusions: Preoperative remP/S ratio and HbA1c were significant predictors of NODMP, enabling the effective stratification of NODMP risk and facilitating the early treatment of the disease.