Statins decrease the risk of acute pancreatitis after endoscopic ultrasound fine-needle aspiration of pancreatic cysts.
- 作者列表："Facciorusso A","Buccino VR","Prete VD","Antonino M","Contaldo A","Muscatiello N
BACKGROUND:Basic and clinical studies suggest that statins may prevent and even ameliorate acute pancreatitis. The present study was to evaluate whether statin decreases the risk of acute pancreatitis in patients undergoing endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts. METHODS:Out of 456 patients with pancreatic cysts referred to our center between 2006 and 2018, 365 were finally included in analyses: 86 were treated with statins and 279 were not at the time of endoscopic ultrasound fine-needle aspiration. We compared the acute pancreatitis incidence between the two groups, and we also compared other complications such as bleeding and infections. RESULTS:Median age was 64 years [interquartile range (IQR) 62-69] and median cyst size was 24 mm (IQR, 21-29). The most frequent histology was intraductal papillary mucinous neoplasm (45.3% and 42.3% in the two groups, respectively; P = 0.98). All 13 patients experiencing post-endoscopic ultrasound acute pancreatitis were from the control group (4.7%), of which 3 were classified as severe pancreatitis. None of statin users developed post-procedural acute pancreatitis (odds ratio: 0.15; 95% confidence interval: 0.03-0.98; P = 0.03). No difference was registered with regard to severe pancreatitis and other complications. CONCLUSIONS:Statins exert a beneficial role in preventing acute pancreatitis in patients with pancreatic cysts undergoing endoscopic ultrasound-guided fine-needle aspiration. If confirmed in prospective trials, our findings may pave the way to an extensive use of statins as prophylactic agents in pancreatic interventional endoscopy.
背景: 基础和临床研究表明，他汀类药物可以预防甚至改善急性胰腺炎。本研究旨在评估他汀类药物是否能降低接受内镜超声引导下细针穿刺胰腺囊肿患者发生急性胰腺炎的风险。 方法: 在 456 和 2006年转诊到我们中心的 2018 例胰腺囊肿患者中，365 例最终被纳入分析: 86 例接受他汀类药物治疗，279 例在超声内镜细针穿刺时未接受治疗。比较两组患者的急性胰腺炎发生率，同时比较出血、感染等并发症。 结果: 中位年龄 64 岁 [四分位距 (IQR) 62-69]，中位囊肿大小为 24mm (IQR，21-29)。最常见的组织学是导管内乳头状黏液性肿瘤 (两组分别为 45.3% 和 42.3%; p = 0.98)。13 例超声内镜后急性胰腺炎患者均来自对照组 (4.7%)，其中 3 例为重症胰腺炎。他汀类药物使用者均未发生术后急性胰腺炎 (比值比: 0.15; 95% 置信区间: 0.03-0.98; p = 0.03)。在重症胰腺炎和其他并发症方面没有登记差异。 结论: 他汀类药物对行超声内镜引导下细针穿刺的胰腺囊肿患者预防急性胰腺炎具有有益作用。如果在前瞻性试验中得到证实，我们的研究结果可能为广泛使用他汀类药物作为胰腺介入内镜检查的预防药物铺平道路。
METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.
METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
METHODS:PURPOSE:Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS:We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS:Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS:Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.