Background-We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR). Methods and Results-Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES.Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10.

In the majority of bifurcation lesions treated with the crush technique, the smallest minimum stent area appeared at the SB ostium. This may contribute to a higher restenosis rate at this location.

Background-Little is known about causes of intimal hyperplasia (IH) after sirolimus-eluting stent (SES) implantation.Methods and Results-Intravascular ultrasound was performed in 24 lesions with intra-SES restenosis and a comparison group of 25 nonrestenotic SESs. To assess stent strut distribution, the maximum interstrut angle was measured with a protractor centered on the stent, and the visible struts were counted and normalized for the number of stent cells. In SES restenosis patients, minimum lumen site was compared with image slices 2.5, 5.0, 7.5, and 10.0 mm proximal and distal to this site. The minimum lumen site had a smaller IVUS lumen area at follow-up (2.7Ϯ0.9 versus 6.2Ϯ1.9 mm 2 ; PϽ0.01), larger maximum interstrut angle (135Ϯ39°versus 72Ϯ23°; PϽ0.01), larger IH area (3.4Ϯ1.5 versus 0.6Ϯ1.1 mm 2 ; PϽ0.01) and thickness (0.7Ϯ0.3 versus 0.1Ϯ0.2 mm; PϽ0.01) at maximum interstrut angle, and fewer stent struts (4.9Ϯ1.0 versus 6.0Ϯ0.5; PϽ0.01) even when normalized for the number of stent cells (0.78Ϯ0.15 versus 0.97Ϯ0.07; PϽ0.01). Compared with nonrestenotic SES, the restenosis lesions also had a smaller minimal lumen area, larger IH area, thicker IH at maximum interstrut angle, fewer stent struts, and larger maximum interstrut angle. Multivariate analysis identified the number of visualized stent struts normalized for the number of stent cells and maximum interstrut angle as the only independent IVUS predictor of IH cross-sectional area (PϽ0.01 and PϽ0.01), minimum lumen area (PϽ0.01 and PϽ0.01), and IH thickness (PϽ0.01 and PϽ0.01). Conclusions-The number and distribution of stent struts affect the amount of neointima after SES implantation.

Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02. Additionally, we analyzed the molecular mechanisms that facilitated the regulation of PD-L1 expression in these cell lines. We observed that when AsPC-1, MIA PaCa-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein expression was enhanced. Similarly, the mRNA level of PD-L1 was upregulated in the AsPC-1 and Pan02 cells when stimulated by each of the three anticancer agents. The phosphorylation of STAT1 and an increase in total STAT1 were also observed in the AsPC-1 cells when stimulated by each anticancer agent. In response to JAK2 inhibitor treatment, PD-L1 upregulation induced by the anticancer agents was reduced in a dose-dependent manner. These results suggest that i) the JAK2/STAT1 pathway is involved in the anticancer agent-mediated PD-L1 transcription; and ii) the anticancer agents altered the tumor immune response which may induce tumor immune escape. These findings can have an influence on the design of treatments that combine chemotherapy and immunotherapy.