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No significant differences were found between the two groups regarding clinicopathological factors, such as age, gender, tumor location, depth of tumor invasion, lymph node metastasis, histological grade, Dukes' stage, and vessel invasion.

Several cancer-related gene candidates were identified using microarray data from the four cell lines (HCT116, SW480, DLD1, KM12SM)

Purpose: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs.Experimental Design: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs. LPACs were isolated by flow cytometry. Treatment resistance (radio- and chemotherapy) and the capacity of LPACs to act as CSCs were analyzed. Microarray analysis was performed to reveal genes related to treatment resistance. The prognostic impact of potent genes was examined in 190 patients with colorectal cancer.Results: LPACs had a significantly increased capacity for radioresistance and chemoresistance (5-fluorouracil and oxaliplatin), significantly lower reactive oxygen species activity, and significantly increased sphere formation capacity compared with non-LPACs. The number of cells in the G0–G1 phase was significantly higher among LPACs. Subcutaneous injection of as few as 20 LPACs led to tumor formation in immunologically incompetent mice. Microarray analysis revealed that the expression of EP300-interacting inhibitor of differentiation 3 (EID3) was significantly increased in LPACs. In vitro assay revealed that EID3 positively controlled cell proliferation and treatment resistance. The high expression of EID3 was an adverse prognostic indicator in patients with colorectal cancer (P = 0.0400).Conclusions: LPACs have characteristic treatment resistance and act as CSCs in colorectal cancer. In addition, EID3 is one of the potential regulators of treatment resistance in colorectal cancer and may be a potential therapeutic target. Clin Cancer Res; 22(21); 5277–86. ©2016 AACR.

Described markers expression, CD133, CD166, Lgr5 (Alexa Fluor® 647 channel, BD Biosciences) and EpHB2 (PE channel, R&D systems, Minneapolis, MN, USA), were compared between LPACs and non-LPACs. The LPACs clearly showed up-regulation of several CSC markers including CD133, CD166, Lgr5 and EpHB2. Especially, Lgr5 was enriched in all cell lines (HCT116; 0.7% (non-LPACs) vs 18.1% (LPACs), SW480; 0.2% vs 28.1% and DLD1; 2.3% vs 45.2%).

EID3 was identified by microarray analysis. The expression of EID3 was confirmed by PCR and western blotting. (A) The mRNA expression of EID3 was significantly enriched in LPACs of HCT116, KM12SM and DLD1 compared to non-LPACs, except SW480 which just missed statistical significance (p=0.0555). (B) Western blotting was also performed for checking the expression of EID3 protein in LPACs and non-LPACs using EID3 antibody (Abcam, Cambridge, UK, ab124447), but the evaluation was difficult, because expression of EID3 is low in humans as per previous report (31, 32). * p

(A) The efficiency of over-expression was validated by expression of mRNA. The expression of EID3 was significantly higher in cells with EID3 　expression vector than cells with control vector. (B) The efficiency of down-regulation was confirmed by mRNA. The expression of EID3 was significantly lower in cells with double-stranded RNA duplexes targeting human EID3 than cells with negative control siRNA. * p

Introduction: There are little data concerning the long-term outcome of single-incision laparoscopic surgery (SILS) for colon cancer. Therefore, we investigated not only the short-term outcomes but also the long-term outcomes of SILS for right-side colon cancer. Methods: We retrospectively compared short- and long-term outcomes of SILS and conventional laparoscopic surgery (CLS) for right-sided colon cancer in our institution. Intergroup differences of short-term outcomes were evaluated using χ2 or Fisher exact tests and 2-sample Student t tests. The disease-free survival rates (long-term outcome) of stage II and III patients were estimated using the Kaplan-Meier method and compared using log-rank tests. Results: There were 290 operations conducted for right-side (cecum and ascending) colorectal cancers from April 2011 to July 2018. Open surgery was performed in 12 cases from start to the operation. SILS was performed in 196 cases and CLS in 55 cases. One patient underwent intraoperative conversion from SILS to laparotomy for bleeding control. In addition, 1 port was added to SILS in 3 cases. These 4 cases were included in the analysis as the SILS group according to the principle of intent to treat. Background: Factors including age, gender, body mass index, performance status, and tumor stage were not statistically different between the SILS and CLS groups. In short-term outcomes, the number of harvested lymph nodes was not statistically different. SILS required less operating time (p < 0.001) and resulted in a reduced bleeding volume (p < 0.001). There was no statistical difference in the frequency of overall complications (p = 0.06). The disease-free survival of stage II and III patients was not statistically different between the 2 groups. Conclusions: With the proper adaptation of SILS by an experienced surgeon, the short- and long-term outcomes of SILS were not inferior to those of CLS. Therefore, SILS could be a treatment option for right-sided colon cancer.

INTRODUCTION Late stent thrombosis caused by delayed vascular healing and prolonged local inflammation were major drawbacks of 1st generation drug-eluting stents (DES). Strut design, biocompatibility of polymer, and drug-release profiles were improved in 2nd and 3rd generation DES. Accordingly, the indications for percutaneous coronary intervention with DES have been expanded to more complex patients and lesions. Despite these improvements, significant barriers such as greater flexibility in the duration of dual-antiplatelet therapy (DAPT) as well as reducing long-term stent-related events remain. To achieve ideal short- and long-term results, these existing limitations need to be overcome. AREAS COVERED We will discuss the current limitations of coronary DES and how they might be overcome from pathological and clinical viewpoints. EXPERT OPINION Optimizing DAPT duration after stent implantation and prevention of in-stent neoatherosclerosis are two major issues in current DES. Overcoming these drawbacks is a prerequisite towards achieving better short- and long-term clinical outcomes. New technologies including platform design, polymer types, and anti-proliferative agent itself might lead to further improvements. Although the initial experience with bioresorbable scaffold/stents (BRS) was disappointing, positive results of clinical studies regarding novel BRS are raising expectations. Overall, further device innovation is desired for overcoming the limitations of current DES.

c-Fos is a useful marker gene of neuron activation for neuroscience and physiology research. The mechanism and function of neural networks have been elucidated using c-Fos reporter knock-in (KI) mice, but the small size of the mice makes it difficult to perform surgical procedures on specific brain regions. On the other hand, there is a large amount of accumulated data on behavioral studies using rats. Thus, the generation of c-Fos reporter rat is expected, but it is difficult to generate gene-modified rats. Furthermore, c-Fos gene abnormality is expected to be severe in rats, as shown in homozygous of c-Fos knockout (KO) mouse, but such analysis has rarely been performed and is not certain. This study generated c-Fos-deficient rats using CRISPR/Cas, with 1067 bp deletion including exon 1 of the c-Fos gene. Homozygous c-Fos KO rats had growth latency and the same tooth and bone abnormality as homozygous c-Fos KO mice but not heterozygous c-Fos KO rats. Therefore, the c-Fos gene in rats is expected to have the same function as that in mice, and the generation of c-Fos reporter KI rats is further anticipated.

Catheter-based renal denervation is a novel treatment approach for patients with hypertension and initial unblinded trials have shown promising results. The Paradise™ Ultrasound Renal Denervation System (ReCor Medical, CA, USA) is an ultrasound-based catheter with a distal balloon that acts as a coolant to protect the renal arterial wall. This device received CE-mark in 2012. Randomized, sham-controlled trials and postmarket studies have shown promising efficacy and safety results. Currently, three additional ongoing randomized, sham-controlled trials are underway in the USA, Europe, Japan and Korea, and the results will be pivotal in device approval in some of these countries. These studies with larger numbers of patients and longer duration of follow-up are needed to further confirm the safety and efficacy of this device.

A seven-year-old female common marmoset (Callithrix jacchus) presented with weight loss. Imaging revealed a left thoracic mass, confirmed at necropsy. Histology and immunohistochemistry suggested a well-differentiated pulmonary adenocarcinoma. No evidence of local lymphovascular invasion or distant metastasis was observed. This is the first report of pulmonary adenocarcinoma in marmosets.

Background The robotic system has been applied in the treatment of gastric cancer (GC), and the procedure has been found to be safe and feasible. Situs inversus totalis (SIT) is a relatively rare autosomal recessive congenital anomaly. We successfully performed robot-assisted proximal gastrectomy (RAPG) and handsewn double-flap esophagogastrostomy for GC in a patient with SIT. Case presentation A 71-year-old woman was referred to us with an asymptomatic ulcerative lesion in the upper body of the stomach. Computed tomography revealed that she had SIT. She was diagnosed with cT1bN0M0, cStageIA gastric cancer. RAPG with lymph node dissection and handsewn double-flap esophagogastrostomy was performed. Robotic surgery enabled the surgeon to perform the surgery without changing his position and experiencing any confusion resulting from the patient’s reversed anatomy. It took 448 min, and no intraoperative complications occurred. Her postoperative course was uneventful; she was discharged on postoperative day 10. The final pathologic report showed pT1b1N0M0, pStage IA. Conclusions This is the first case describing RAPG with handsewn double-flap esophagogastrostomy for a SIT patient with early GC.

Introduction Cerebrovascular events are one of the most serious consequences after transcatheter aortic valve replacement (TAVR). More than half of the cerebrovascular events following TAVR are due to procedure-related emboli. Embolic protection devices (EPDs) have the potential to decrease cerebrovascular events during TAVR procedure. However, randomized controlled trials (RCTs) have not conclusively determined if EPDs are effective, likely because of small number of patients enrolled. However, meta-analyses and propensity-matched analyses from large registries have shown efficacy and suggest the importance of EPDs in prevention of stroke during TAVR and perhaps other structural heart procedures. Areas covered This review will focus on clinical and histopathologic studies examining the efficacy, safety, and histopathologic device capture findings in the presence and absence of EPDs during TAVR procedures. Expert opinion Clinical studies have not conclusively determined the efficacy of EPDs. Current ongoing large-scale RCT (PROTECTED TAVR [NCT04149535]) has the potential to prove their efficacy. Histopathological evaluation of debris captured by EPDs contributes to our understanding of the mechanisms of TAVR procedure-related embolic events and suggests the importance of preventing cerebral embolization of debris released during this and other structural heart procedures.

Software packages for computing seismic traveltimes and raypaths in an isotropic, spherically symmetric, Earth model are well known and widely used. However, even though the theory for transversely isotropic (TI), spherically symmetric, models has been known since the late 1960s, readily available programs for traveltime calculations are restricted to isotropic models. We have developed a new software package, ANISOtime, for computing seismic traveltimes and raypaths in laterally homogeneous, TI, spherical media. This package calculates traveltime tables for both immediate and subsequent use. ANISOtime has both graphical user interface and command-line interface modes. The package is available for free public download. As it offers cross-platform compatibility through Java 8, it runs on Windows, macOS, Unix, and Linux.

Background This study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA). Methods Twelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium. Results The distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA. Conclusions The pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.

Background and aims We developed a deep learning (DL) model for automated atherosclerotic plaque categorization using optical frequency domain imaging (OFDI) and performed quantitative and visual evaluations. Methods A total of 1103 histological cross-sections from 45 autopsy hearts were examined to compare the ex vivo OFDI scans. The images were segmented and annotated considering four histological categories: pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), and healed erosion/rupture (HER). The DL model was developed based on pyramid scene parsing network (PSPNet). Given an input image, a convolutional neural network (ResNet50) was used as an encoder to generate feature maps of the last convolutional layer. Results For the quantitative evaluation, the mean F-score and IoU values, which are used to evaluate how close the predicted results are to the ground truth, were used. The validation and test dataset had F-score and IoU values of 0.63, 0.49, and 0.66, 0.52, respectively. For the section-level diagnostic accuracy, the areas under the receiver-operating characteristic curve produced by the DL model for FC, PIT, FA, and HER were 0.91, 0.85, 0.86, and 0.86, respectively, and were comparable to those of an expert observer. Conclusions DL semantic segmentation of coronary plaques in OFDI images was used as a tool to automatically categorize atherosclerotic plaques using histological findings as the gold standard. The proposed method can support interventional cardiologists in understanding histological properties of plaques.

Objective: Reported associations between kidney risk variants (G1 and G2) in APOL1 (apolipoprotein L1), encoding APOL1, and cardiovascular disease have been conflicting. We sought to explore associations of APOL1 risk variants with cause of sudden death using the CVPath Sudden Death Autopsy Registry. Approach and Results: APOL1 haplotypes and causes of sudden death, as determined through autopsy and histopathology, were obtained for 764 Black subjects. Genotyping revealed APOL1 risk alleles in 452 of 764 (59%) subjects with 347 (77%) subjects carrying one risk allele and 105 (23%) subjects harboring 2 risk alleles. APOL1 risk allele carrier status was associated with a significantly increased risk of coronary thrombosis due to plaque rupture, versus noncarriers (odds ratio for rupture, 1.655 [95% CI, 1.079–2.539]; P =0.021). Histological examinations showed coronary plaques in carriers of 2 APOL1 risk alleles had larger necrotic cores compared with noncarriers (necrotic core area/total plaque area: 46.79%±6.47% versus 20.57%±5.11%; P =0.0343 in ruptured plaques, and 41.48%±7.49% versus 18.93%±3.97%; P =0.0342 in nonruptured plaques), and immunohistochemical and immunofluorescent staining revealed APOL1-positive areas localized primarily to the necrotic core. Conclusions: APOL1 risk alleles were independently associated with an increased risk of thrombotic coronary death due to plaque rupture. Our results suggest that carriers of both 1 and 2 APOL1 risk alleles have greater accumulation of APOL1 protein within culprit plaques and greater necrotic core sizes than noncarriers. These findings suggest that APOL1 plays a role in determining plaque stability.

Atherosclerosis-based ischemic heart disease is still the primary cause of death throughout the world. Over the past decades there has been no significant changes in the therapeutic approaches to atherosclerosis, which are mainly based on lipid lowering therapies and management of comorbid conditions such as diabetes and hypertension. The involvement of macrophages in atherosclerosis has been recognized for decades. More recently, a more detailed and sophisticated understanding of their various phenotypes and roles in the atherosclerotic process has been recognized. This new data is revealing how specific subtypes of macrophage-induced inflammation may have distinct effects on atherosclerosis progression and may provide new approaches for treatment, based upon targeting of specific macrophage subtypes.We will comprehensively review the spectrum of macrophage phenotypes and how they contribute to atherosclerotic plaque development and progression.Various signals derived from atherosclerotic lesions drive macrophages into complex subsets with different gene expression profiles, phenotypes, and functions, not all of which are understood. Macrophage phenotypes include those that enhance, heal, and regress the atherosclerotic lesions though various mechanisms. Targeting of specific macrophage phenotypes may provide a promising and novel approach to prevent atherosclerosis progression.

Astroviruses are often associated with gastrointestinal diseases in mammals and birds. Murine astrovirus (MuAstV) is frequently detected in laboratory mice. Previous studies on MuAstV in mice did not report any symptoms or lesions. However, little information is available regarding its pathogenicity in immunodeficient mice. Therefore, in this study, we experimentally infected germ-free NOD.Cg-PrkdcscidIl2rgtm1Sug/ShiJic (NOG) mice, which are severely immunodeficient, with MuAstV. Germ-free mice were used for experimental infection to eliminate the effects of intestinal bacteria. Mice in each group were then necropsied and subjected to PCR for MuAstV detection, MuAstV RNA quantification in each organ, and histopathological examination at 4 and 28 days post inoculation (DPI). Tissue samples from the small intestine were examined by transmission electron microscopy. No symptoms or abnormalities were detected in any mice during necropsy. The MuAstV concentration was highest in the lower small intestine, where it increased approximately 8-fold from 4 to 28 DPI. Transmission electron microscopy revealed circular virus particles of approximately 25 nm in diameter in the cytoplasm of the villous epithelial cells of the lower small intestine. Histopathological examination did not reveal any abnormalities, such as atrophy, in the intestinal villi. Our results suggest that MuAstV proliferates in the villous epithelial cells of the lower small intestine and has weak pathogenicity.

Background Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied. Objectives The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes. Methods A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification. Results The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs. Conclusions Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked—proximally and distally—by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.

Objective: Persons with HIV have double the risk of developing cardiovascular disease compared with the general population. A persistent and heightened immune response to cytomegalovirus coinfection may be one contributing factor, but the relationship between cytomegalovirus replication, virus-specific immune cells, and plaque burden is unclear. Approach and Results: We assessed the relationship between CD4 + T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known cardiovascular disease. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1 + ~GPR56 + ~CD57 + (ie, C~G~C) + CD4 + T cells ( P =0.03), which is a marker combination associated with antiviral and cytotoxic responses. In addition, a median of 14.4% (IQR, 4.7%–32.7%) of the C~G~C + CD4 + T-cells expressed antigen receptors that recognized a single cytomegalovirus glycoprotein-B epitope. Using immunofluorescence staining, we found that CX3CR1 + CD4 + T cells were present in coronary plaque from deceased HIV-positive persons. C~G~C + CD4 + T cells were also present in cells isolated from the aorta of HIV-negative donors. Conclusions: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4 + T-cells expressing the C~G~C surface marker combination associated with antiviral and cytotoxic responses. These cells can be cytomegalovirus-specific and are also present in the aorta.

A 47-year-old woman, who had been diving 6 times, panicked during diving training and surfaced suddenly after a 15-minute dive at a depth of 19 meters. She had nausea, vomiting, and headache immediately after surfacing. Decompression sickness (DCS) was suspected, and she was transported to the emergency room (ER) of our hospital by ambulance. Upon arrival, she had mild consciousness disturbance and hypoxia requiring oxygen. Her symptoms remained. She initially received 12 L per minute of oxygen and rapid infusion for DCS. However, ultrasound study showed no air bubbles in the inferior vena cava or portal vein. Trunk computed tomography (CT) showed infiltrative lesions in the bilateral lung fields without gas in any vessels. The diagnosis was drowning with alternobaric vertigo. She was treated with an antibiotic without recompression therapy. The patient's dizziness and vomiting subsided quickly. Her post-admission course was uneventful and she was discharged to her home on the 9th hospital day. We report a case in which ultrasound was useful for differentiating between DCS and drowning. When patients have symptoms after diving, confirmation of the presence of gas in the heart or vessels using ultrasound in the acute phase is important for the diagnosis of DCS.

Introduction: In-stent restenosis (ISR) has been one of the biggest limitations to the success of percutaneous coronary intervention for the treatment of coronary artery disease (CAD). The introduc...

Humanized mice are widely used to study the human immune system in vivo and develop therapies for various human diseases. Human peripheral blood mononuclear cells (PBMC)-engrafted NOD/Shi-scid IL2rγnull (NOG) mice are useful models for characterization of human T cells. However, the development of graft-versus-host disease (GVHD) limits the use of NOG PBMC models. We previously established a NOG-major histocompatibility complex class I/II double knockout (dKO) mouse model. Although humanized dKO mice do not develop severe GVHD, they have impaired reproductive performance and reduced chimerism of human cells. In this study, we established a novel beta-2 microglobulin (B2m) KO mouse model using CRISPR/Cas9. By crossing B2m KO mice with I-Ab KO mice, we established a modified dKO (dKO-em) mouse model. Reproductivity was slightly improved in dKO-em mice, compared with conventional dKO (dKO-tm) mice. dKO-em mice showed no signs of GVHD after the transfer of human PBMCs; they also exhibited high engraftment efficiency. Engrafted human PBMCs survived significantly longer in the peripheral blood and spleens of dKO-em mice, compared with dKO-tm mice. In conclusion, dKO-em mice might constitute a promising PBMC-based humanized mouse model for the development and preclinical testing of novel therapeutics for human diseases.

Introduction Sarcomatoid carcinoma (SC) is a rare subtype of malignant neoplasm with a poor prognosis that involves both carcinomatous and sarcomatous components. Although it may develop in various organs, SC in the large intestine has rarely been reported. It is not rare for patients with SC to have distant metastasis, reflecting its highly aggressive oncologic features, but cases with brain metastasis on initial visit are rare. In this report, we described a case of SC in the transverse colon with brain metastases whose initial symptom was neurological disorder, and reviewed 31 reported cases of SC. Case presentation A 70-year-old man was admitted to our hospital with the chief complaints of gait disorder and severe dizziness. Head magnetic resonance imaging revealed tumor masses in the anterior lobe and cerebellum. A large tumor in the transverse colon was detected by colonoscopy and abdominal enhanced computed tomography (CT), and was diagnosed as undifferentiated adenocarcinoma by histology. Laparoscopic extended right hemicolectomy was performed to remove the obstruction, and the resected specimens revealed an invasive tumor consisting of a mixture of carcinomatous and sarcomatous components. According to the immunopathological study, the patient was diagnosed with SC. The clinical course was extremely aggressive, and the patient died on the 28th postoperative day because of disease progression. Conclusion To the best of our knowledge, this is the first case of SC in the transverse colon with a neurological disorder derived from brain metastases. This experience may contribute to the guidance regarding proper therapeutic options for SC.

Deformation of phyllosilicate can control the dynamics of the Earth's crust. The phenomenological relationship between stress and deformation is known for some typical phyllosilicates; however, the underlying physics originating from the crystal structures is poorly understood. In this study, the deformation mechanism of pyrophyllite along basal planes was revealed through density functional theory calculations and atomic-scale theory of friction. The stable and metastable interlayer structures formed by interlayer slide were consistent with the experimental results reported previously by high-resolution transmission electron microscopy. The difference in potential energies between stable and metastable interlayer structures can be interpreted as the difference in the stacking of dioctahedral sheets between the adjacent layers. The estimated friction coefficient of the pyrophyllite between adjacent layers was consistent with the results of atomic force microscopy, suggesting that atomic-scale friction can be adequately estimated by this method. The calculated shear stress in our simulations has a linear relationship with the normal stress and has no significant crystallographic dependence on sliding direction along the basal planes. The crystallographic isotropy of interlayer friction is explained by the absence of interlayer cations in pyrophyllite, while muscovite showed crystallographic anisotropy as observed in previous studies. The macroscopic friction of a single crystal of pyrophyllite was estimated from atomic-scale friction by using the area of contact. The macroscopic friction coefficient of ideal interlayer sliding was estimated to be 0.134, which was smaller than a reported value (0.276) in shear experiments conducted for wet polycrystalline gouge layers. This difference can be primarily explained by the degree of orientation of pyrophyllite particles in the gouge layers. The friction coefficient estimated by a simple model of randomly oriented pyrophyllite gouge layer was 0.203 ± 0.001, which was similar to the reported value of 0.276 and clearly smaller than the values (0.6–0.85) of common minerals estimated by the empirical Byerlee's law. These results indicate that weak interlayer friction of phyllosilicates has a large effect on the low frictional strength of gouge layers in natural faults. Our methodology and results are useful for understanding the physics behind the phenomenological friction laws of phyllosilicate gouge.

Purpose: To evaluate glistening and long-term stability of five commercially available intraocular lenses. Methods: This experimental study evaluated the SN60WF (Alcon), XY1 (Hoya), NS-60YG (NIDEK), ZCB00V (Johnson & Johnson Vision) and AN6KA (Kowa) intraocular lenses. To generate glistenings, intraocular lenses were immersed in physiological saline at 50°C for 2 h, then left in situ at 35°C and removed at regular intervals over 24 h. Stability of the intraocular lens material was assessed by immersing intraocular lenses into vials of purified water placed at 100°C for 115 days, which simulated 20-year ageing. Gas chromatography–mass spectrometry was used to detect leached compounds. Results: Almost no glistenings were observed for the AN6KA. Glistenings were observed in the remaining intraocular lenses after 3 h. The number of glistenings gradually disappeared by 6 h for all intraocular lenses except SN60WF (12 h). Only the NS-60YG and ZCB00V intraocular lenses had no changes in weight or dimensions. Gas chromatography–mass spectrometry detected phenethyl alcohol in XY1 and SN60WF, 2-phenoxyethanol in AN6K and no compounds in the remaining intraocular lenses. A peak shift due to the carbonyl group between 1600 and 1700 cm−1 was detected for the SN60WF and AN6K intraocular lenses only. Conclusion: SN60WF had the most numerous glistenings that resolved over a longer duration. The long-term stability test confirmed elution of the intraocular lens material–derived compounds and signs of degradation for the XY1, SN60WF and AN6K intraocular lenses. NS-60YG and ZCB00V showed no signs of deterioration due to ageing. Differing manufacturing methods likely play a role in the stability of intraocular lenses.

Advanced gastric cancer with liver metastasis is classified as stage IV disease and is generally treated with systemic chemotherapy. Despite recent advances in chemotherapy regimens, the prognosis for gastric cancer with liver metastasis is poor. Recent studies reported the effectiveness of upfront chemotherapy followed by conversion surgery for gastric cancer with liver metastasis. Here, we report a case of an advanced stage IV gastric cancer with liver metastasis treated with upfront systemic chemotherapy followed by conversion surgery, which resulted in pathological complete response and good prognosis.A 79-year-old man diagnosed with human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer with multiple liver metastases. He underwent systemic chemotherapy with capecitabine, cisplatin, and trastuzumab. After 14 courses of chemotherapy, the primary tumor and liver metastases shrank, suggesting a partial response. We performed distal gastrectomy with D2 dissection plus lateral hepatic segment resection. Pathological examination revealed no residual tumor cells in the primary or metastatic sites, which indicated a pathological complete response. The postoperative course was uneventful. The patient was discharged on postoperative day 8. Adjuvant S-1 chemotherapy was started on postoperative day 46 and given for 1 year. The patient has been alive and recurrence-free for approximately 5 years after surgery.This case shows the possibility of conversion surgery after systemic chemotherapy for stage IV advanced gastric cancer with liver metastasis.

The patient was a 75-year-old woman who was referred to our department because she had type 3 advanced gastric cancer on the posterior wall of the gastric body. Following a thorough examination, she was diagnosed as cT4aN3M1 (#16a1 int, #16b2 lat), cStage Ⅳ, an unresectable advanced gastric cancer with multiple extranodal lymph node metastases. As radical resection was not possible, chemotherapy(SOX therapy)was started. After the start of chemotherapy, the main lesion and metastatic lymph nodes shrank markedly. At the time of 7 courses, it was judged that R0 resection by conversion surgery was possible, and surgical treatment was performed. The patient underwent sub-total gastrectomy with D2 dissection and para-aortic lymph node dissection. The specimen was submitted for pathological examination and showed no residual tumor component including the main lesion and dissected lymph nodes, indicating a complete pathological response. She was started on S-1 as adjuvant chemotherapy on postoperative day 51 and has been recurrence-free for approximately 5 months after surgery.

We report a case of sphenoid bone metastasis from breast cancer detected with diplopia, as first site of recurrence. Forty- year-old woman with left breast cancer underwent breast-conserving surgery and sentinel lymph node biopsy. The diagnosis was papillotubular carcinoma, pT1pN0, ER(+), PgR(+), HER2(-). Tweleb years later, the examination of diplopia revealed left abducens nerve palsy for sphenoid bone metastasis from breast cancer. Radiation therapy(a total dose of 36 Gy with VMAT)was administrated as topical treatment, but diplopia did not improve. After that, systemic treatment was performed, and 2 years and 6 months have passed since the recurrence was found, she is still alive. We need to be careful of orbital metastasis as a symptom of metastasis from breast cancer.

We report a case of non-exposed endoscopic wall-inversion surgery(NEWS)performed by TANKO technique for gastric GIST. A 52-year-old man was diagnosed as having gastric GIST. A 2 cm-sized tumor was found in the lesser curvature of the middle body of the stomach, and an endoscopic biopsy revealed GIST. A 2.5 cm umbilical incision was made and TANKO surgery was performed. After seromyotomy around the tumor, the outer serosal muscularis was sutured closed to invert the tumor into the stomach. The inverted tumor was resected from the stomach wall and recovered using endoscopic techniques. NEWS is an operation developed to resect a tumor without exposing it into the abdominal cavity and is expected to avoid the risk of postoperative abdominal abscess and peritoneal dissemination. On the other hand, the TANKO is a procedure with excellent plastic technique and can be performed in this operation.

Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland.State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip codes. Area deprivation index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart.Subjects from most disadvantaged neighborhoods (i.e., ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods (i.e., ADI ≤ 7; n = 857; 46.07 ± 14.10 vs 47.78 ± 13.86 years; P = 0.02) and were more likely Black or women. They were less likely to die from cardiac causes of death (61.8% vs 67.7%; P = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% vs 25.1%, P = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race.Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in sudden cardiac death.

A woman in her 30s visited our hospital complaining primarily of melena. Colonoscopy revealed the presence of a type 1 tumor in 2 cm from anal verge. Contrast-enhanced CT showed an unresectable massive liver metastasis in the left lobe of the liver and another metastasis in the right lobe. The patient received front-line chemotherapy with Leucovorin, fluorouracil, oxaliplatin, and irinotecan(FOLFOXIRI)plus bevacizumab(BEV). A year later, a marked reduction of liver metastases and primary lesions was confirmed by CT scan imaging. A multidisciplinary team recommended resection of the liver metastases followed by laparoscopic intersphincteric resection for primary lesions. However, after 1 year, a recurrence was diagnosed in the liver; hence, FOLFOXIRI plus BEV was reintroduced for volume reduction. The patient underwent a repeat hepatectomy since enough volume reduction was confirmed. One year later, she experienced a re-relapse of the metastasis in the liver. Currently, she is still undergoing chemotherapy following 7 years since the first visit. Long-term survival can be expected following surgical treatment during chemotherapy.

The patient is an 85-year-old female who had previously undergone a mastectomy for right breast cancer at the age of 42 years. In September 2020, she visited our hospital with a chief complaint of a chest wall tumor. Physical examination revealed a 3×3 cm ulcerative lesion on the right side of the center chest wall. She underwent a skin biopsy of the tumor under local anesthesia and was diagnosed with a recurrence of right breast cancer(ER positive, PR positive, HER2 negative). PET-CT revealed localized skin thickening on the right side of the sternum and FDG accumulation in the same area, with no other findings suggestive of distant metastasis. Treatment was started with anastrozole and is still ongoing. In this article, we report a very rare case of recurrence 43 years after surgery.

Laparoscopic surgery is a safe, minimally invasive, and effective approach in managing abdominal malignancies. Laparoscopic anatomical resection has been covered by insurance in Japan since 2016. Here, we have reported the short-term outcomes of gallbladder cancer in laparoscopic cholecystectomy, gallbladder bed resection, or S4a/S5 liver resection with lymph node dissection.Between May 2012 and December 2020, 28 patients underwent laparoscopic cholecystectomy for gallbladder cancer at Kansai Rosai Hospital. Two patients underwent laparoscopic choledochotomy with lymph node dissection, 6 patients underwent gallbladder bed resection, and 7 patients underwent S4a/S5 liver resection. The control group included 13 patients who received open surgery between July 2010 and November 2019. The patient age was 74.2 and 74.4 years, while the male to female ratio was 19/24 and 8/5 in the laparoscopic and open surgery groups, respectively. According to the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the pathological stage was 0/Ⅰ/Ⅱ/Ⅲ A/ⅢB/ⅣA/ⅣB in 4/17/13/4/2/1/2 and 0/1/2/3/1/1/5 patients(p=0.0100)in the laparoscopic and open surgery groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2101001).The laparoscopic surgery group had an average operation time of 223.3 minutes, an estimated blood loss of 18.7 g, and a hospital stay of 8.5 days. The open surgery group had an average operation time of 514.5 minutes, an estimated blood loss of 1,274.3 g, and a hospital stay of 33.9 days. There was no postoperative bleeding or bile leakage in both groups. After laparoscopic cholecystectomy, the 5-year disease-free survival rate was 100% among Stage 0 or Ⅰ patients, 64.8% among Stage Ⅱ patients, and 0% in Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage 0 or Ⅰ patient and 66.7% among Stage Ⅱ patients. The 1-year overall survival rate was 50% among Stage Ⅲ or Ⅳ patients. After laparoscopic liver resection with lymph node dissection, the 5-year disease-free survival rate was 100% among Stage Ⅰ or Ⅱ patients and 66.7% among Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage Ⅰ or Ⅱ patients and 62.5% among Stage Ⅲ or Ⅳ patients.Laparoscopic cholecystectomy in Stage 0 or Ⅰ patients and laparoscopic gallbladder bed resection or S4a/S5 liver resection with lymph node dissection were safe and effective approaches to gallbladder cancer management.