Association between venous thromboembolism and acute pancreatitis: An analysis from the nationwide inpatient sample.
- 作者列表："Chung WS","Lin CL
BACKGROUND AND AIMS:Acute inflammation of the pancreas may trigger a systemic inflammatory response and initiate coagulation. Few studies have been conducted on the association between venous thromboembolism (VTE) and acute pancreatitis (AP). We investigated the incidence and risk of VTE in patients with AP. METHODS:We conducted a retrospective cohort analysis for the nationwide AP cohort. We identified 91 786 patients with AP and 183 557 controls who were frequency-matched according to sex, age (5-y interval), and index year from the National Health Insurance Research Database between 2000 and 2008. The patients and controls were followed until diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE), death or the end of 2011. RESULTS:The nationwide cohort study showed that patients with AP exhibited a higher incidence of VTE (13.1 vs 5.65 per 10 000 person-y) than did the controls. After covariates were controlled for, the patients with AP had a 1.88-fold higher risk of VTE than did the controls (adjusted hazard ratios [aHR] = 1.88; 95% confidence intervals [CI] = 1.68-2.10). The incidence rates of DVT and PE were higher in the patients with AP than in the controls, irrespective of sex, age or comorbidity. The patients with AP exhibited a 1.86-fold higher aHR of DVT (95% CI = 1.63-2.12) and a 1.92-fold higher aHR of PE (95% CI = 1.59-2.31) than did the controls. CONCLUSION:Patients with AP exhibited a significantly higher risk of VTE than did the controls.
背景和目的: 胰腺的急性炎症可能引发全身炎症反应并启动凝血。关于静脉血栓栓塞症 (VTE) 和急性胰腺炎 (AP) 之间的关系的研究很少。我们调查了 AP 患者 VTE 的发生率和风险。 方法: 我们对全国 AP 队列进行了回顾性队列分析。我们从 786 和 2000年的国家健康保险研究数据库中确定了 91 183 例 AP 患者和 557 2008 例对照，根据性别、年龄 (5-y 间期) 和指数年份进行频率匹配。随访患者和对照直至确诊为深静脉血栓形成 (DVT) 或肺栓塞 (PE) 、死亡或 2011年底。 结果: 全国队列研究显示，AP 患者的 VTE 发生率 (13.1 vs 5.65/10 000 人-y) 高于对照组。控制协变量后，AP 患者发生 VTE 的风险是对照组的 1.88 倍 (校正风险比 [aHR] = 1.88; 95% 置信区间 [CI] = 1.68-2.10)。AP 患者 DVT 和 PE 的发生率高于对照组，与性别、年龄或合并症无关。AP 患者表现为 DVT 的 aHR 高 1.86 倍 (95% CI = 1.63-2.12)，PE 的 aHR 高 1.92 倍 (95% CI = 1.59-2.31) 比对照组还多。 结论: AP 患者发生 VTE 的风险显著高于对照组。
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.