Pancreas最新文献

Objectives: Chronic pancreatitis (CP) is a fibro-inflammatory disorder characterized by abdominal pain and exocrine and endocrine pancreatic insufficiency resulting in significant morbidity. This study evaluates the impact of geospatial parameters, assessed using the Social Vulnerability Index (SVI), a tool comprising sixteen social attributes, on CP outcomes, including opioid use.

Methods: We conducted a retrospective analysis of CP patients with available addresses followed at our pancreas center. We reviewed demographics, clinical variables including number of CP flares, local complications, pancreatic function, and healthcare-resource utilization (HRU) including imaging, endoscopic procedures, and surgeries, and outpatient opioid prescriptions measured in morphine milligram equivalents (MME). Regression analysis was performed to assess the association between outcomes and SVI [divided into 4 quartiles (I-IV; IV being most vulnerable].

Results: Among 324 CP patients followed over 8 years, we noted trends of higher dependence on governmental insurance or no insurance among patients in higher SVI quartiles (III/IV vs. I/II) but no differences in demographics, comorbidities, or etiology of CP. In patients residing in more vulnerable SVI quartiles, we noted significantly higher frequency of hospitalizations for CP flares and lower daily MME. Rates of exocrine and endocrine pancreatic dysfunction and HRU were similar across all SVI quartiles.

Conclusions: Despite multidisciplinary guideline-based care, residence in the most vulnerable neighborhoods may be associated with less opioid use and more frequent CP flares, suggesting possible inadequate pain control in these patients. These findings should guide prospective investigation of the impact of geospatial social determinants of health in CP and efforts to mitigate the above disparities.

Abstract: Mutant KRAS activation occurs in most of pancreatic cancer (PDAC) which induce the sensitivity to ferroptosis of PDAC cells, but the underlying mechanism is still poorly understood. Here, we show how KRAS acts in signaling to activate transcription factor FOSL1, which promotes the expression of the iron uptake receptor TFRC. In PDAC cells, repression of TFRC by KRAS/FOSL1 signaling inhibited intracellular iron levels, thereby restricting the occurrence of ferroptosis. Furthermore, the KRAS/FOSL1/TFRC axis can make the PDAC cells vulnerable to alteration of the iron level in the tumor microenvironment. Our study highlights a pivotal mechanism of PDAC ferroptosis through iron metabolism and supports a new therapeutic strategy for PDAC with superior potential.

Objectives: The best strategy for non-functioning, sporadic, G1-G2 pancreatic neuroendocrine tumors ≤2 cm is unknown. An active surveillance is usually recommended. The PROMID and the CLARINET studies proved the value of somatostatin analogue (SSA) treatment in advanced gastro-entero-pancreatic neuroendocrine tumors. Aim of this study is to assess the value of SSA in PanNET≤2 cm.

Methods: We retrospectively collected data from 72 patients with sporadic non-functioning G1-G2 PanNETs≤2 cm, that were either treated with somatostatin analogues (n = 31) or underwent active surveillance (n = 41) at our Institution.

Results: At a median follow-up of 53.7 months, the median progression free survival was not reached in the treatment group versus an estimated PFS of 85 months in the control group (HR 0.11, p = 0.01), with a rate of progression or death up to 21.9% in the active surveillance group. Additionally, in the group of patients treated with somatostatin analogues the response rate was 16.1% with one complete response.

Conclusions: Our monocentric experience demonstrated a significant antiproliferative activity of somatostatin analogues in patients with sporadic, non-functionating G1-G2 PanNETs ≤2 cm delaying tumor progression and distant spread in small lesions that sometimes may reveal unpredictable aggressiveness.

Objectives: We analyzed annual surgical trends for benign chronic pancreatitis (CP), studying specifically mortality, morbidity, and pancreatic fistula rates. We also aimed to identify predictors of pancreatic fistula formation.

Methods: For this analysis, we used data from the American College of Surgeons National Surgical Quality Improvement Program from 2014 through 2021. The study included patients who underwent surgery for benign CP. Data collected included patient demographics, preoperative variables, and postoperative outcomes. Data were analyzed with univariate and multivariate analyses, with significance defined as P ≤ .05.

Results: Over the study period, the number of pancreatic surgical procedures increased 49.3%, although surgery specifically for CP declined by 31.7%. The rate of pancreatic fistula formation decreased 44.9%, and mortality decreased 31.9%. Significant predictors of a pancreatic fistula included no diabetes, preoperative sepsis, soft texture of the pancreatic gland, and greater patient weight.

Conclusion: Surgery for benign CP decreased substantially despite the established efficacy of surgical intervention for long-term pain management. The concurrent decline in mortality and rates of pancreatic fistula formation suggest advances over the study years in surgical and postoperative care.

Objectives: There is a paucity of data regarding the use of neoadjuvant therapy in pancreatic body or tail ductal adenocarcinomas. Given the differing tumor biology and aggressive nature of pancreatic body or tail adenocarcinomas, patients presenting with these tumors may benefit from upfront resection.

Methods: A retrospective cohort study was performed analyzing patients who underwent distal pancreatectomy for pancreatic ductal adenocarcinoma between January 2013 and June 2022. Patients who underwent upfront resection were compared with those who underwent neoadjuvant therapy.

Results: Forty-one patients underwent upfront distal pancreatectomy, whereas 40 patients underwent neoadjuvant therapy before curative intent resection. Neoadjuvant therapy did not improve overall survival (37 vs 34 months, P = 0.962) or disease-free survival (13 vs 15 months, P = 0.414), as compared with upfront resection. There was no significant difference in the rate or R 0 resection or postoperative outcomes.

Conclusion: No significant improvement in survival was demonstrated for patients undergoing neoadjuvant therapy for pancreatic ductal adenocarcinoma of the pancreatic body or tail when compared with upfront resection. Considering the potential for disease progression given the more aggressive tumor biology of pancreatic body and tail adenocarcinomas, appropriate surgical candidates should be offered upfront resection to provide the best chance of survival and cure.

Objectives: Although splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extrasplanchnic venous thromboembolism (ESVT) is inadequately studied. Here, we aim to explore the incidence of venous thromboembolism (VTE) in acute necrotizing pancreatitis (ANP) and the associated mortality.

Methods: Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate International Classification of Diseases, 10th Revision, Clinical Modification codes. The primary outcome was development of acute ESVT within 1 month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities.

Results: During the study period, 17,942 (7.11%) patients were diagnosed with ANP, and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTEs, 61% were ESVT with or without SVT, and 63% (n = 1799) were SVT. Ninety-day mortality (16.3% vs 5.7%; risk ratio [RR], 2.86; 95% confidence interval, 2.29-3.56) and 30-day rehospitalization (31% vs 19%; RR, 1.63; 95% confidence interval, 1.49-1.79) were higher in patients with ESVT compared with non-VTE patients. Sixty percent of patients with ESVT were on OAC, and OAC use was associated with lower 90-day mortality (8.9% vs 19.4%; RR, 0.46) without increased risk of adverse events (acute gastrointestinal bleeding, intracranial bleeding, or need for transfusion).

Conclusions: Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay and in the immediate ambulatory period.

Objective: The role of Krüppel-like transcription factor 4 ( KLF4 ) mutations in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study clarified the rate and effect of KLF4 mutations in IPMN with concomitant PDAC.

Materials and methods: DNA was extracted from 65 formalin-fixed and paraffin-embedded samples from 52 patients including 13 IPMNs with concomitant PDAC and 39 IPMNs alone. A comprehensive screening using next-generation sequencing and then targeted sequencing for KLF4 , GNAS , and KRAS mutations were performed.

Results: In next-generation sequencing screening, KRAS mutations were observed in all samples except for one, GNAS mutation in 2 IPMNs with concomitant PDAC, and a KLF4 mutation in 1 IPMN with concomitant PDAC. Targeted sequence detected KLF4 mutations in 11 of the 52 IPMNs. Concomitant PDAC developed only in the nonintestinal, noninvasive, and branch-duct IPMNs, and KLF4 mutations were more frequent in this IPMN type than in the other type. For this IPMN type with KLF4 mutation, PDAC-prediction sensitivity, specificity, and accuracy were 63%, 82%, and 79%, respectively.

Conclusion: For selected IPMNs with nonintestinal, noninvasive, and branch-duct, genetic assessment might be helpful for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.