Yu Hatano

Proton Pump Inhibitor Induction of Gastric Cobblestone-like Lesions in the Stomach

Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed. The biopsy specimens from patients with gastric cobblestone-like lesions (GCLLs) were examined histopathologically. Patients This study analyzed 171 patients who underwent upper gastrointestinal endoscopy after more than 6 months of PPI use in Mitsugi Public General Hospital from January 1, 2015, to March 31, 2016. Results Of the 171 patients, 60 (35.1%) had GCLLs and 111 (64.9%) did not. There were no significant between-group differences in age, sex, duration of PPI use, and receipt of Helicobacter pylori eradication therapy. Atrophic gastritis of the corpus was significantly less frequent in the GCLL than in the non-GCLL group (55.0% vs. 47.8%, p=0.0097). Among the GCLL group, histological examinations of 24 patients revealed cystic dilation of the fundic gland in 19 (79.2%), parietal cell hyperplasia in 18 (75.0%), and cytoplasmic vacuolation in 7 (29.2%). Conclusion GCLLs occurred frequently in long-term PPI users, especially in patients without atrophic gastritis. The pathological findings of GCLLs included parietal cell hyperplasia and fundic gland cysts. The clinical importance of these new lesions remains uncertain, but they should be observed carefully.

Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These findings revealed that OGCs in the tumor environment promoted tumor growth and lymphangiogenesis, at least in part, by secreting VEGF-C.

The Hypercholesterolemia Paradox in Percutaneous Coronary Intervention: An Analysis of a Multicenter PCI Registry

Objective The aim of this study was to assess the relationship between hypercholesterolemia (HC) and clinical events through a percutaneous coronary intervention (PCI) registry. HC is a well-known independent risk factor for long-term cardiovascular events after PCI. However, it has been reported to be associated with a lower risk of adverse events in patients with cancer or acute coronary syndrome. Methods We analyzed the relationship between HC and adverse events in patients treated with everolimus-eluting stents (EESs) through the Tokyo-MD PCI study (an all-comer, multicenter, observational registry). The propensity score method was applied to select two groups with similar baseline characteristics. Results The unadjusted population included 1,536 HC patients and 330 non-HC patients. Propensity score matching yielded 314 matched pairs. After baseline adjustment, the outcomes of HC patients were significantly better than those of the non-HC patients with respect to the primary endpoint, which was a combination of mortality from all causes, nonfatal myocardial infarction (MI), nonfatal neurological events, and major bleeding [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.81; p=0.002], and the secondary endpoints, which included a combination of mortality from all causes, nonfatal MI, and nonfatal neurological events (HR 0.59, 95% CI 0.39-0.88; p=0.01), and major bleeding (HR 0.42, 95% CI 0.20-0.88; p=0.02). A subgroup analysis showed age as an interaction factor for the primary endpoint (interaction p=0.035). Conclusion HC was associated with better outcomes in patients who underwent EES implantation, even after baseline adjustment.

Effectiveness of the proximal optimization technique for longitudinal stent elongation caused by post‐balloon dilatation

OBJECTIVES To evaluate the effectiveness of the proximal optimization technique (POT) to prevent longitudinal stent elongation. BACKGROUND The mechanism of stent elongation, which occurs after post-balloon dilation, is still unclear. METHODS A total of 103 lesions treated with optical coherence tomography guided coronary intervention between May 2013 and November 2017 were retrospectively analyzed. Lesions were divided according to the circumferential degree of malapposition at the stent edge immediately after deployment into well-apposed group (<180°) and malapposed group (≥180°). Post-dilation was performed from distal to proximal within the stent until August 2016 (non-POT cohort), and POT was applied thereafter (POT cohort). In the POT cohort, post-dilation was done at the proximal portion of the stent with sufficiently large balloon to minimize malapposition followed by distal dilatations. Stent elongation length was defined as the change in stent length from stent deployment to after post-dilatation. RESULTS In the non-POT cohort, 72 lesions, including 54 lesions in the well-apposed group and 18 in the malapposed group were analyzed. Stent elongation length was significantly longer in the malapposed group than in the well-apposed group (1.51 ± 1.34 mm vs 0.13 ± 0.84 mm, P < 0.01). In the POT cohort, 31 lesions including 21 in the well-apposed group and 10 in the malapposed group were analyzed. Stent elongation length was not significantly different between the groups (-0.09 ± 0.91 mm vs 0.30 ± 0.99 mm, P = 0.29). CONCLUSIONS Malapposition of the stent edge is responsible for longitudinal stent elongation caused by post-dilatation. POT appeared to effectively prevent longitudinal stent elongation.

Effect of drug-coated balloon on stent restenosis, neointimal proliferation, and coronary dissection: an optical coherence tomography analysis

Aim The aim of this study was to assess the acute and mid-term effects of drug-coated balloon (DCB) in terms of the healing process of non-flow-limiting dissections and changes in the neointimal area after DCB treatment using frequency domain optical coherence tomography (FD-OCT). Patients and methods Thirty-six consecutive patients with in-stent restenosis pretreated with a scoring balloon were evaluated (19 and 17 patients with and without a DCB, respectively). FD-OCT was performed before and after each procedure during percutaneous coronary intervention and at 6 months of follow-up. Results Clinical characteristics and baseline FD-OCT findings were comparable between the two groups. No patient required stent implantation because of low-pressure DCB-related dissections. In the acute phase, the DCB distributed paclitaxel to the vessel wall without increasing dissections. The DCB did not reduce the neointimal area by itself. At 6 months, more dissections healed in the DCB group (−4.5±2.3 vs. −2.7±1.3, P=0.02). The DCB group showed less change in the neointimal area (−0.04±0.92 vs. 1.06±1.57 mm2, P=0.03). Conclusion The low-pressure DCB was not intended to expand the lumen, but instead to attach paclitaxel to the vessel wall by using FD-OCT examination. The DCB reduced the number of dissections and prevented neointimal proliferation during the mid-term follow-up.

TCT-235 Effect of Additional Lower-speed Rotational Atherectomy on Acute Lumen Gain in vivo and in vitro: Evaluation using OFDI

The association between the platform speed and acute lumen gain remains unknown. The purpose of this study is to evaluate the effect of additional lower-speed rotational atherectomy (RA) following conventional high-speed RA on acute lumen gain using sequential optical frequency domain imaging (OFDI