Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From The Insppire Study.
小儿急性复发性或慢性胰腺炎的临床和实践变化: 来自 Insppire 研究的报告。
- 作者列表："Dike CR","Zimmerman B","Zheng Y","Wilschanski M","Werlin SL","Troendle D","Shah U","Schwarzenberg SJ","Pohl J","Perito ER","Ooi CY","Nathan JD","Morinville VD","McFerron B","Mascarenhas M","Maqbool A","Liu Q","Lin TK","Husain SZ","Heyman MB","Gonska T","Giefer MJ","Gariepy CE","Fishman DS","Bellin M","Barth B","Abu-El-Haija M","Lowe ME","Uc A
OBJECTIVE:To determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) sites. STUDY DESIGN:Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson Chi-Square test. Differences in disease burden were compared by Kruskal-Wallis test. RESULTS:Of 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (p < 0.0001); white race in Northeast (p = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (p = 0.0002 and p = 0.011 respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (p = 0.002). Gallstones were more frequent in South (p = 0.002). ERCP and CT imaging were more commonly utilized in US compared to non-US (p < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly because total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (p < 0.0001). CONCLUSION:This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-US sites need to be further explored.
目的: 确定儿童急性复发性胰腺炎 (ARP) 和慢性胰腺炎 (CP) 的临床特征和处理是否在 INSPPIRE (国际儿童胰腺炎研究小组: 寻找治愈方法) 中存在差异网站。 研究设计: 从 INSPPIRE 收集数据，并按美国地区和 “非美国” 网站进行分析。通过 Pearson 卡方检验比较组间差异。通过 Kruskal-Wallis 检验比较疾病负担的差异。 结果: 在 479 名受试者中，西部 121 名 (25%) 、中西部 151 名 (32%) 、东北 45 名 (9 )、 78 名 (16%) 南部和 84 名 (18%) 在非美国网站。西班牙裔在南方更常见 (p
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.