Pancreas最新文献

Objectives: To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT).

Methods: Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor.

Results: OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs. 27.5 months, P = 0.014. DSS: 63.3 vs. 33.0 months, P = 0.014. RFS: 20.3 vs. 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS.

Conclusions: This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.

Methods: The review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist.

Results: 15 studies including 147 patients (adult n = 71/paediatric n = 76) reported on CGM use post-TP (n = 42) and TPIAT (n = 105). 4 were randomized controlled trials and 10 observational studies. 6 studies evaluated CGM use in the peri-operative and 6 in the immediate post-operative period (n = 8) with variable follow-up (14 hours -20 months). CGM was used as a stand-alone device (8 studies) which allowed assessment of dynamic islet function and detection of hypoglycemia (n = 1) resulting in lower glucose levels (n = 1). 6 studies evaluated insulin pump with CGM with reduction in post-operative mean glucose (n = 4), and hypoglycaemic episodes (n = 2). There were no patient reported outcome measures (PROMs) or quality of life (QoL) measures reported.

Conclusions: CGM can be used following TP for glucose monitoring and/or linked with insulin pump device in the peri-operative period with improved glycaemic control. However, the data are limited by short follow-up and lack of PROMs and QoL measures.

Objectives: Non-functioning Pancreatic Neuroendocrine Tumors (NF-PNET) are rare tumors with heterogeneous biology. Radiology and serum biomarkers are used for post-resection surveillance; however, no universally established protocol exists. Serum Chromogranin A (CgA) concentration is elevated in NF-PNET, and generally correlates with burden of disease; many CgA studies include mixed gastrointestinal and pancreatic populations. We sought to review the NF-PNET literature with focus on post-resection surveillance and hypothesized that CgA is useful for surveillance after NF-PNET resection.

Methods: Comprehensive English literature review by PICO criteria (P-human NF-PNET patients; I-pancreatectomy; C- none; O- CgA correlation with disease recurrence).

Results: Four studies yielded granular data for resected NF-PNET patients. From 333 patients, 113 recurred and 110 (97%) had elevated CgA. Additional 7 studies with mixed gastro-entero-pancreatic NET included 269 NF-PNET patients. In these patients, CgA uniformly predicted disease extent.

Conclusions: Serum Chromogranin A correlates with disease extent in NF-PNET, and is useful for surveillance after resection of NF-PNET.

Abstract: Pancreatic diseases pose significant diagnostic and therapeutic challenges necessitating robust biomarkers for accurate diagnosis, management and monitoring of pancreas function. Pancreas function can be measured with direct (invasive) and indirect tests. However, both approaches do not allow continuous disease monitoring to identify disease progression or therapeutic response. We demonstrate literature evidence suggesting that trypsin, an important pancreatic digestive enzyme, holds promise as such a continuous biomarker. On one hand, assessment of trypsin concentration in the serum sensitively and specifically detects pancreas inflammation; whereas on the other hand, declining trypsin levels in serum showed good correlation with direct pancreatic function tests to identify exocrine pancreatic insufficiency. With this comprehensive review, we aimed to evaluate the existing evidence on the utility of trypsin as a continuous biomarker, spanning from acute to chronic pancreatitis and pancreas function, highlighting its potential in monitoring disease evolution on an individual patient level.

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.