Atherosclerotic plaque behind the stent changes after bare-metal and drug-eluting stent implantation in humans: Implications for late stent failure?

Background and aims The natural history and the role of atherosclerotic plaque located behind the stent (PBS) are still poorly understood. We evaluated the serial changes in PBS following bare-metal (BMS) compared to first-generation drug-eluting stent (DES) implantation and the impact of these changes on in-stent neointimal hyperplasia (NIH). Methods Three-dimensional coronary reconstruction by angiography and intravascular ultrasound was performed after intervention and at 6–10-month follow-up in 157 patients with 188 lesions treated with BMS (n = 89) and DES (n = 99). Results There was a significant decrease in PBS area (−7.2%; p  <  0.001) and vessel area (−1.7%; p  <  0.001) after BMS and a respective increase in both areas after DES implantation (6.1%; p  <  0.001 and 4.1%; p  <  0.001, respectively). The decrease in PBS area significantly predicted neointimal area at follow-up after BMS (β: 0.15; 95% confidence interval [CI]: 0.10–0.20, p  <  0.001) and DES (β: 0.09; 95% CI: 0.07–0.11; p  <  0.001) implantation. The decrease in PBS area was the most powerful predictor of significant NIH after BMS implantation (odds ratio: 1.13; 95% CI: 1.02–1.26; p = 0.02). Conclusions The decrease in PBS area after stent implantation is significantly associated with the magnitude of NIH development at follow-up. This finding raises the possibility of a communication between the lesion within the stent and the underlying native atherosclerotic plaque, and may have important implications regarding the pathobiology of in-stent restenosis and late/very late stent thrombosis

Arterial Remodeling and Endothelial Shear Stress Exhibit Significant Longitudinal Heterogeneity Along the Length of Coronary Plaques

Atherosclerosis is determined by both systemic risk factors and local vascular mechanisms. The arterial remodeling in response to plaque development plays a key role in atherosclerosis. Compensatory expansive remodeling is an adaptive mechanism that maintains lumen patency as a plaque develops. In contrast, excessive expansive remodeling, signifying an enlargement in vascular and lumen volume as a result of local plaque buildup, is a consistent attribute of high-risk plaques. Local hemodynamic factors, in particular low endothelial shear stress (ESS), is an intensely proinflammatory and proatherogenic stimulus and largely accounts for the spatially diverse distribution of atherosclerotic plaques. However, plaque, remodeling and ESS have hitherto been investigated only in the cross-sectional arterial axis and their distribution in the longitudinal axis of individual plaques has not been characterized

Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans

Background: In‐stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated. Methods and Results: We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three‐dimensional coronary reconstruction was performed in 374 post‐PCI patients at baseline and 6 to 10 months follow‐up as part of the PREDICTION Study. Each vessel was divided into 1.5‐mm‐long segments, and we calculated the local ESS within each stented segment at baseline. At follow‐up, we assessed ISH and the occurrence of a clinically indicated repeat PCI for in‐stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare‐metal stents (BMS), 104 (42.3%) sirolimus‐eluting stents, and 42 (17.1%) paclitaxel‐eluting stents. In BMS, low ESS post‐PCI at baseline was independently associated with ISH (β=1.47 mm2 per 1‐Pa decrease; 95% CI, 0.38–2.56; P<0.01). ISH was minimal in drug‐eluting stents. During follow‐up, repeat PCI in BMS was performed in 21 stents (8.5%). There was no significant association between post‐PCI ESS and in‐stent restenosis requiring PCI. Conclusions: Low ESS after BMS implantation is associated with subsequent ISH. ISH is strongly inhibited by drug‐eluting stents. Post‐PCI ESS is not associated with in‐stent restenosis requiring repeat PCI. ESS is an important determinant of ISH in BMS, but ISH of large magnitude to require PCI for in‐stent restenosis is likely attributed to factors other than ESS within the stent

Pretreatment Glasgow prognostic score as a predictor of outcomes in nivolumab-treated patients with advanced gastric cancer.

In Japan, South Korea, and Taiwan, nivolumab might provide overall survival benefits for patients with advanced gastric cancer. However, it is effective only in a limited number of patients. The Glasgow prognostic score is an indicator of the systematic inflammatory response and nutritional status. This study aimed to investigate the ability of the Glasgow prognostic score and other markers to predict the outcomes of patients treated with nivolumab. We reviewed the medical records of patients treated for advanced gastric cancer and who received nivolumab between February 2015 and June 2019 at Hyogo Cancer Center. The patients were categorized into two groups according to their Glasgow prognostic scores. Overall, 53.3% and 46.7% of the patients were assigned to groups with Glasgow prognostic scores of 0 and 1/2, respectively. The median durations of progression-free and overall survival of the participants were 2.3 and 5.7 months, respectively. The patients with a Glasgow prognostic score of 0 had significantly higher median overall survival than those with scores of 1 or 2 (16.4 vs. 4.2 months; p = 0.0006). This observation suggests that a pretreatment Glasgow prognostic score of 0 is associated with better outcomes, and this scoring system may be used as a predictor of outcomes in patients with advanced gastric cancer treated with nivolumab

The impact of nutritional status in nivolumab-treated patients with advanced esophageal cancer.

Although phase III trials have reported improved overall survival in patients with advanced esophageal squamous cell carcinoma following treatment with nivolumab, as compared with chemotherapy (paclitaxel or docetaxel), the treatment was effective only in a limited number of patients. Therefore, the aim of this study is to determine whether there is a correlation between nutritional status (Glasgow prognostic score, prognostic nutritional index, and neutrophil-to-lymphocyte ratio) and prognosis of advanced esophageal cancer in patients treated with taxane or nivolumab therapy. The medical records of 35 patients who received taxane monotherapy (paclitaxel or docetaxel), for advanced esophageal cancer between October 2016 and November 2018 (taxane cohort) were reviewed. The clinical data of 37 patients who received nivolumab therapy between March 2020 and September 2021 (nivolumab cohort) were collected. The median overall survival was 9.1 months for the taxane cohort and 12.5 months for the nivolumab cohort. In the nivolumab cohort, patients with good nutritional status had significantly better median overall survival than those with poor nutritional status (18.1 vs. 7.6 months, respectively, p = 0.009, classified by prognostic nutritional index, 15.5 vs. 4.3 months, respectively, p = 0.012, classified by Glasgow prognostic score), whereas the prognosis of the patients treated with taxane therapy was less affected by the nutritional status. This suggests that the pretreatment nutritional status of patients with advanced esophageal cancer is a key factor for successful outcomes, especially for treatment with nivolumab

Clinical Factors of Delayed Perforation after Endoscopic Submucosal Dissection for Gastric Neoplasms

Background. Delayed perforation is a rare but severe complication of endoscopic submucosal dissection (ESD) for early gastric neoplasm (EGN). The aim of this study was to clarify clinical factors related to delayed perforation after ESD. Methods. A total of 1158 consecutive patients with 1199 EGNs underwent ESD at our hospital between January 2000 and December 2015. Univariate analysis was used to identify clinicopathological factors related to delayed perforation. Moreover, duration of cautery needed for hemostasis was measured by comparison between perforated and nonperforated points in patients with delayed perforation. Results. Delayed perforation occurred in 5 of 1158 consecutive patients with 1199 EGNs who underwent ESD (0.42%). All cases were diagnosed within 24 h after ESD and recovered with conservative management. On univariate analysis, location in the upper stomach was the factor most significantly associated with delayed perforation (P<0.01). Duration of cautery needed for hemostasis was significantly longer at perforated points (9 s) than at nonperforated points (3.5 s) in five patients. Conclusions. Location in the upper stomach was the risk factor most prominently associated with delayed perforation after ESD for EGNs. In addition, delayed perforation appears associated with excessive electrocautery for hemostasis