Pancreas最新文献

Background: The advent of highly effective modulator therapies (HEMT), namely elexacaftor, tezacaftor, and ivacaftor (ETI), has resulted in substantial improvements in lung function, growth, and quality of life for people with cystic fibrosis (PwCF). However, the understanding of the impact of ETI on gastrointestinal (GI) disease burden is evolving. This study aims to describe and compare the prevalence of GI manifestations, prescribed GI medications, and GI procedures between 2 time periods, pre-ETI and post-ETI approval, in children with CF (CwCF) and adolescents with CF.

Methods: This is a retrospective cohort study utilizing TriNetX, a multicenter database. The study includes patients between 6 to 21 years old with ICD-10 diagnostic codes for CF and a prescription for pancreatic enzyme replacement therapy (PERT) to match disease severity. We included 4 years before, and 4 years after the release of the ETI combination therapy.

Results: When comparing CwCF taking PERT, on or off ETI, the prevalence of diagnostic codes for chronic pancreatitis, constipation, unspecified noninfective gastroenteritis, and colitis significantly decreased after ETI use (all P < 0.0001). The prevalence of other luminal disorders, liver disorders, and acute pancreatitis did not differ between the 2 groups. The prevalence of prescribed medications, including mucolytics, vitamins, PPI, and antidiarrheal, was similar for both groups except for a reduction in prescribed laxatives ( P -value = 0.0001). The prevalence of GI procedures was also similar in both groups.

Conclusions: The reduction in constipation and noninfective gastroenteritis and colitis is important as GI symptoms are linked to the quality of life of CwCF. There remains a great clinical need to evaluate the effects of ETI on GI disorders, especially as the age of initial use of this therapy decreases and the duration of use increases.

Background: Splanchnic venous thrombosis (SVT) involving veins in the vicinity of the pancreas is a significant complication of acute pancreatitis (AP). The natural history of SVT, especially the rates of recanalization, is poorly understood.

Aim: This study aimed to evaluate the natural history of SVT in AP, with a focus on recanalization rates and identifying predictors of nonrecanalization.

Materials and methods: This was an observational study in which patients with SVT in the setting of AP were included. Patients were followed for at least 6 months. Recanalization was assessed using Doppler ultrasound or CT imaging, and outcomes were classified as complete recanalization, partial recanalization, or nonrecanalization. Statistical analysis was done to identify predictors of nonrecanalization.

Results: Among 814 patients with AP, 92 (11.3%) developed SVT. Of these, 70 met the inclusion criteria. The mean age was 38.1 years, with 92.8% male predominance. Alcohol was the most common etiology (62.8%). The retropancreatic splenic vein was the most commonly affected vessel. At follow-up, complete recanalization was observed in 54.3% of cases, partial recanalization in 2.9%, while 42.8% showed no evidence of recanalization. Therapeutic anticoagulation was administered to 20% of patients without significantly influencing recanalization rates. A BISAP score ≥2 was a significant predictor of nonrecanalization ( P =0.007).

Conclusion: Most patients with SVT following AP demonstrate spontaneous recanalization. A key predictor for nonrecanalization is the severity of pancreatitis.

Objectives: To investigate the therapeutic mechanisms of Sanhuang Xiexin Decoction (SHXXD) in treating severe acute pancreatitis-associated lung injury (PALI) by modulating the NF-κB signaling pathway.

Materials and methods: Active components and potential targets of SHXXD were identified through the TCMSP database. A protein-protein interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo and in vitro experiments were performed to evaluate the anti-inflammatory effects of SHXXD in CAE- and LPS-induced mouse models and cellular experiments. NF-κB pathway activation and inflammatory cytokine expression were analyzed by Western blot and Quantitative Real-Time PCR (qPCR).

Results: Fifty-two active components of SHXXD were identified, including quercetin, baicalin, emodin, and berberine. Based on molecular docking results, these components were found to bind strongly with key inflammatory proteins such as TNF, IL6, IL1B, and MMP9. In vivo experiments showed significant reductions in serum amylase and lipase levels and inhibited NF-κB pathway activation and inflammatory cytokine expression.

Conclusions: SHXXD exerts therapeutic effects in treating severe acute pancreatitis-associated lung injury by modulating the NF-κB signaling pathway, making it a potential alternative treatment for PALI. Its active components, including quercetin and baicalin, reduce inflammation.

Chronic pancreatitis (CP) progressively destroys and fibroses the pancreatic parenchyma, ultimately impairing exocrine and endocrine functions. Acinar-to-ductal metaplasia (ADM), the transformation of acinar cells into duct-like cells, plays a critical role in the progression of CP. This review first provides an overview of the plasticity of various cell types in the exocrine pancreas. It then delves into the mechanisms underlying ADM, focusing on its driving factors, including genetic mutations, environmental influences, and signaling pathways such as Notch. Finally, it discusses emerging therapeutic strategies, such as small molecule targeted drugs, nanomaterial-based drug delivery platforms, and cell regeneration therapies, that effectively alleviate inflammation and fibrosis. Although progress has been made, significant challenges remain in understanding the complex mechanisms of ADM and in ensuring the safety and efficacy of these therapies. This review aims to provide an in-depth understanding of the role of ADM in CP and to pave the way for efficacious therapeutic options.

Background: Chronic pancreatitis (CP) complications in adults are successfully managed with endoscopic retrograde cholangiopancreatography (ERCP). Data is limited on the success of ERCP in children with CP. We reviewed our experience to ascertain the success, safety, and effectiveness of ERCP for relieving pain and its effect on exocrine and endocrine insufficiency.

Methods: Retrospective analysis of a prospectively kept database of children (≤18 years) with CP who underwent therapeutic ERCP between 2010-2020, were reviewed. Clinical details, laboratory and radiological investigations, procedural details, and follow-up data were retrieved from manual and electronic records. Categorical and numerical data were expressed as proportion and mean ± standard deviation (SD).

Results: Sixty-five children (60% males); age 12.8±2.9years, were included. The most common etiology was idiopathic (n=45,69%). Technical, endoscopic, and clinical success rates were 95.3%,92.3%, and 85.6% respectively. Only 4 patients (6.1%) had major complications. Over a median follow-up of 24 months, therapeutic ERCP resulted in significant pain relief, with non-progression of exocrine and endocrine insufficiency. Recurrence of symptoms was noted in 10%, which were managed successfully with repeat ERCP.

Conclusion: Therapeutic ERCP is a safe and effective therapy for the management of CP in children with significant improvement in pain and could influence stabilization of exocrine, and endocrine functions.

Introduction: Total pancreatectomy with islet autotransplantation (TPIAT) is performed for the most disabling cases of recurrent acute pancreatitis and chronic pancreatitis. Post-TPIAT, patients often report gastrointestinal (GI) symptoms suggestive of dysmotility and small intestinal bacterial overgrowth. The goal of this study was to characterize patient reported outcomes related to GI health and quality of life (QoL) after TPIAT.

Methods: Patients ≥18 years of age who underwent TPIAT at the University of Minnesota since July 2006 were eligible for enrollment. In addition to providing demographic information, participants completed the following questionnaires electronically: National Institutes of Health (NIH) Patient Reported Outcomes Measurement System GI Symptom Scale, RAND 36-Item Short Form Survey, and the NIH Health Related Quality of Life 14 Survey.

Results: Study surveys were completed by twenty-seven percent (82/300) of patients contacted, at a median of 8 years after surgery. Participants reported significantly more severe belly pain (t-score 57.9, 95% CI 55.1-60.7), gas / bloating (57.7, 56.1-59.2), nausea / vomiting (56.8, 54.6-59.0), and diarrhea (53.6, 51.5-55.8) compared to the general population. A previous diagnosis of small intestinal bacterial overgrowth (SIBO) was associated with more severe belly pain (coefficient 8.54, 95% confidence interval 2.58-14.50, P value=0.006), gas / bloating (5.65, 2.66-8.64, P<0.001), and nausea / vomiting (4.85, 0.34-9.34, P=0.035). More severe nausea / vomiting and diarrhea were negatively associated with several QoL measures.

Conclusion: Post-TPIAT, patients experience severe belly pain, gas / bloating, nausea / vomiting, and diarrhea at higher rates compared to the general population. Patients who report a diagnosis of SIBO were more likely to have these symptoms with exception of diarrhea. Nausea / vomiting and diarrhea appear to have the largest impact on QoL measures.

Background: Patients with acute pancreatitis (AP) develop widely variable severity of organ failure. We hypothesized that genetic factors may influence the development of organ failure in AP. In this study, we identify candidate loci associated with organ failure in AP using genome-wide association analyses (GWAS) and transcriptomic analyses.

Methods: Subjects enrolled in the Mass General Brigham Biobank were retrospectively queried to determine those with a history of AP. Patients with AP were categorized according to the presence of respiratory or renal failure during the first week of AP. Patients were further divided into two groups based on the etiology of AP (i.e. biliary AP and AP of all other etiologies) and analyzed separately. Meta-analysis of the 2 groups identified candidate loci with P<1e-05. Genes with eQTLs (expression quantitative trait loci) in candidate loci in immune cells were selected. The differential expression of these genes in AP was assessed using transcriptomic data from the Gene Expression Omnibus (GEO) database.

Results: Overall, 665 patients were identified, of which 211 had biliary AP (199 mild, 12 severe) and 454 had AP of other etiologies (428 mild, 26 severe). Nine candidate loci were identified, with rs12185172 on chromosome 16 having the highest association among all SNPs (beta=1.46, P=1.13e-06). Five genes had eQTLs in the candidate loci. CHD9 (adj. P=5.64e-04), FYB (adj. P= 5.09e-03) and MMADHC (adj. P= 2.44e-03) were differentially-expressed in AP.

Conclusions: We performed a GWAS examining organ failure in AP and identified 9 candidate loci, which did not pass the genome-wide significance threshold. Three candidate genes, CHD9, FYB and MMADHC, were identified through eQTL and differential gene expression analyses. These may represent novel therapeutic targets for organ failure in AP.

Background: Immune checkpoint inhibitors (ICI) are increasingly utilized in cancer management due to their favorable outcomes. Pancreatic injury from ICIs (ICI-PI) is a heterogenous entity ranging from silent lipase elevation to clinical pancreatitis. Its distinct immunologic mechanisms and phenotype position it as a novel form of immune-mediated pancreatic injury.

Methods: We performed a narrative review of the emerging literature on ICI-PI, highlighting its mechanisms, epidemiology, clinical and imaging features, histology, management, outcomes, and critical knowledge gaps.

Results: ICI-PI often appears within months of starting therapy and frequently presents as isolated enzyme elevation rather than acute pancreatitis. Early imaging can be unremarkable, but later scans may show pancreatic volume loss or atrophy. Tissue examination shows neutrophil- and CD8-predominant infiltrates. Unlike other forms of autoimmune pancreatitis (AIP), storiform fibrosis, obliterative phlebitis, granulocytic epithelial lesions, or IgG4-rich plasma cells are not seen. Management focuses on supportive care, exclusion of alternative causes, and a temporary ICI hold for clinical pancreatitis. Corticosteroids are reasonable for symptomatic or radiographically confirmed disease, though evidence for long-term benefit is limited. Rechallenge with ICIs appears feasible in selected patients after recovery, with low recurrence rate observed in available data. Some patients develop delayed exocrine or endocrine insufficiency, underscoring the need for follow-up.

Conclusions: ICI-PI is an uncommon yet clinically important entity that shows a distinct clinicopathologic profile from other forms of AIP. Clear diagnostic criteria, practical treatment pathways, and prospective registries are needed to guide therapy, inform rechallenge decisions, and define long-term outcomes.