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Background: Tip detection-antegrade dissection and re-entry (TD-ADR) technique allows operators to accurately observe both guidewire tip direction and a true lumen in chronic total occlusion (CTO) lesions, while the torque direction of the guidewire on IVUS images does not invariably correspond to that on fluoroscopic images., Case Summary: A 41-year-old man with hypertension who smokes presented with sudden onset of dyspnoea, acute heart failure, and ischaemic findings on electrocardiogram; we performed percutaneous coronary intervention (PCI) for a sub-totally occluded mid-left anterior descending artery lesion. All antegrade wiring attempts failed to enter the distal true lumen followed by subintimal tracking and re-entry technique. Since the lesion re-occluded the next day, we treated the lesion using a novel TD-ADR technique, termed the 'integrated TD-ADR', because of no interventional retrograde channel. This method integrates fluoroscopic and intravascular ultrasound (IVUS) images, ensuring congruence in the torque direction of the guidewire across both modalities and enabling vertical puncture of the stiff guidewire from the extraplaque space to the distal true lumen quickly and precisely. Final angiography showed good results. Five months later, coronary angiography showed that the lesion remained open., Discussion: The integrated TD-ADR technique merges fluoroscopic and IVUS images, allowing operators to torque the guidewire in the same direction on both images. This approach might be more user-friendly than the original technique and has the potential to enhance the success rate of PCI in complex CTO cases. However, further investigations are warranted to address the clinical feasibility and applicability of this technique., Competing Interests: Conflict of interest: T.F. serves as a technical consultant for Terumo; S.K. receives lecture fees from Terumo. The other authors report no conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: T.F. serves as a technical consultant for Terumo; the other authors report no conflicts.

A coronary hematoma, which can sometimes obstruct coronary flow, may be left behind after tip-detection antegrade dissection and reentry. We present a novel bailout technique utilizing subintimal trans-catheter withdrawal technique with the assistance of a stent and a balloon. This technique can be used before performing bailout long stenting or a fenestration procedure with a cutting balloon, which are standard treatments for hematoma, to improve impaired coronary flow caused by a distally extended hematoma., (© 2024 Wiley Periodicals LLC.)

Background: Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and irradiation of light at an excitation wavelength that damages tumor cells without causing significant damage to normal tissue. We developed indocyanine green (ICG)-modified liposomes in which paclitaxel (PTX) was encapsulated (ICG-Lipo-PTX). ICG-Lipo-PTX accumulates specifically in tumors due to the characteristics of the liposomes. The thermal and photodynamic effects of ICG and the local release of PTX by irradiation are expected to induce not only antitumor effects but also cancer immunity. In this study, we investigated the antitumor effects of ICG-Lipo-PTX in breast cancer., Methods: The antitumor effects of ICG-Lipo-PTX were examined in xenograft model mice subcutaneously implanted with KPL-1 human breast cancer cells. ICG-Lipo-PTX, ICG-Lipo, or saline was administered intraperitoneally, and the fluorescence intensity was measured with a fluorescence imaging system (IVIS). Intratumor temperature, tumor volume, and necrotic area of tumor tissue were also compared. Next, we investigated the induction of cancer immunity in an allogeneic transplantation model in which BALB-MC mouse breast cancer cells were transplanted subcutaneously in the bilateral inguinal region. ICG-Lipo-PTX was administered intraperitoneally, and PDT was performed on only one side. The fluorescence intensity measured by IVIS and the bilateral tumor volumes were compared. Cytokine secretory capacity was also evaluated by ELISPOT assay using splenocytes., Results: In the xenograft model, the fluorescence intensity and temperature during PDT were significantly higher with ICG-Lipo-PTX and ICG-Lipo in tumor areas than in nontumor areas. The fluorescence intensity in the tumor area was reduced to the same level as that in the nonirradiated area after two times of irradiation. Tumor growth was significantly reduced and the percentage of necrotic area in the tumor was higher after PDT in the ICG-Lipo-PTX group than in the other groups. In the allograft model, tumor growth on day 14 in the ICG-Lipo-PTX group was significantly suppressed not only on the PDT side but also on the non-PDT side. In addition, the secretion of interferon-γ and interleukin-2 was enhanced, whereas that of interleukin-10 was suppressed, in the ICG-Lipo-PTX group., Conclusion: The PDT therapy with ICG-Lipo-PTX may be an effective treatment for breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ishizuka, Kaibori, Sumiyama, Okamoto, Suganami, Tamura, Yoshii, Sugie and Sekimoto.)

Purpose: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups., Methods: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated., Results: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33-0.78) and 29% (HR: 0.71, 95% CI 0.49-1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29-0.74)., Conclusions: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1., (© 2023. The Author(s).)

Estrogen receptor (ER) expression in breast cancer can change during progression and the treatment, but the mechanism has not been well studied. In this study, we successfully prepared organoids from samples obtained from 33 luminal-type breast cancer patients and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Objectives: Burr entrapment is a potentially life-threatening complication of rotational atherectomy (RA). However, owing to its infrequency, there have been no major reports on burr entrapment. This study aimed to evaluate the incidence, treatment, and outcomes of burr entrapment., Methods: This multicenter retrospective study analyzed patients who had undergone percutaneous coronary interventions (PCIs) and were treated by RA between May 2013 and March 2022., Results: Of the 22 640 PCI procedures, RA was performed in 3195 patients (14.1%), among whom burr entrapment occurred in 22 patients (0.69%). The mean patient age was 78 ± 8.7 years; 64% were male, and 32% were on dialysis. The entrapped burr size was 1.7 ± 0.2 mm, and the burr/artery ratio was 0.6 ± 0.1. In 20 patients (91%), the burr was extracted by strong manual pullback. The other patients underwent balloon angioplasty at the site of the entrapped burr, which might have provided space for successful burr withdrawal. Major adverse cardiac events occurred in 23% of patients. Tamponade requiring pericardiocentesis occurred in two patients (9%). No patients required emergency surgery or suffered an in-hospital death., Conclusions: Burr entrapment occurred in 0.69% of patients who had undergone RA. Most burrs were extracted by a strong manual pullback. None required emergency surgery, and there were no in-hospital deaths. The results provide a treatment approach and prognosis for burr stuck in the use of RA.

Background: When a catheter device is delivered during percutaneous coronary intervention, its passage can be disrupted by a deployed in a coronary artery. However, the condition and details of this phenomenon, that is impeded-by-stent phenomenon (ISP), remain unclear., Methods: We designed a prospective, open-label, single-center, observational study to clarify the incidence, predictors, and clinical impact of ISP in drug-eluting stents (DESs). Two independent operators observed and judged the occurrence of ISP, which was defined as all disturbances to a device delivery by deployed DESs. We consecutively used the Ultimaster™ (Terumo, Tokyo, Japan) DES for one month (109 patients, October 2018), followed by the Synergy™ (Boston Scientific Corporation, Marlborough, MA, USA) DES the next month (119 patients, November 2018)., Results: DESs (2.5-4.0 mm in diameter) were implanted in 230 de novo coronary vessels. ISPs were observed in 17 of 239 stented segments (7.1 %). Multivariate analysis showed that bifurcation lesions (adjusted odds ratio [OR], 4.2; 95 % confidence interval [CI], 1.5-12.6; p = 0.008), predilatation balloon diameter (mm) (OR, 0.2; 95 % CI, 0.1-0.9; p = 0.03), and Ultimaster™ use (OR, 6.0; 95 % CI, 1.9-27.2; p = 0.002) were independent predictors of ISPs. During the 1.5-year follow-up period, no repeat revascularization or stent thrombosis occurred in patients with ISP., Conclusions: ISP itself does not trigger notable clinical outcomes, including repeat revascularization and stent thrombosis. However, caution should be considered regarding the latent risk of procedural complications., Competing Interests: Declaration of competing interest Tsutomu Fujita M.D. is a technical consultant for TERUMO corporation. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Dedicated breast PET (dbPET) systems have improved the detection of small breast cancers but have increased false-positive diagnoses due to an increased chance of noise detection. This study examined whether reproducibility assessment using paired images helped to improve noise discrimination and diagnostic performance in dbPET., Methods: This study included 21 patients with newly diagnosed breast cancer who underwent [ 18 F]FDG-dbPET and contrast-enhanced breast MRI. A 10-min dbPET data scan was acquired per breast, and two sets of reconstructed images were generated (named dbPET-1 and dbPET-2, respectively), each of which consisted of randomly allocated 5-min data from the 10-min data. Uptake spots higher than the background were indexed for the study with visual assessment. All indexed uptakes on dbPET-1 were evaluated using dbPET-2 for reproducibility. MRI findings based on the Breast Imaging-Reporting and Data System (BI-RADS) 2013 were used as the gold standard. Uptake spots that corresponded to BI-RADS 1 on MRI were considered noise, while those with BI-RADS 4b-6 were considered malignancies. The diagnostic performance of dbPET for malignancy was evaluated using four different criteria: any uptake on dbPET-1 regarded as positive (criterion A), a subjective visual assessment of dbPET-1 (criterion B), reproducibility assessment between dbPET-1 and dbPET-2 (criterion C), and a combination of B and C (criterion D)., Results: A total of 213 indexed uptake spots were identified on dbPET-1, including 152, 15, 6, 6, and 34 lesions classified as BI-RADS MRI categories 1, 2, 4b, 4c, and 5, respectively. Overall, 31.9% of the index uptake values were reproducible. All malignant lesions were reproducible, whereas 93.4% of noise was not reproducible. The sensitivities for malignancy for criteria A, B, C, and D were 100%, 91.3%, 100%, and 91.3%, respectively, with positive predictive values (PPVs) of 21.4%, 68.9%, 67.6%, and 82.4%, respectively., Conclusions: Our results demonstrated that reproducibility assessment helped reduce false-positive findings caused by noise on dbPET without lowering the sensitivity for malignancy. While subjective visual assessment was also efficient in increasing PPV, it occasionally missed malignant uptake., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

In this study, we analyzed structural changes in financial markets under COVID-19 to support investors' investment decisions. Because an explanation of these changes is necessary to respond appropriately to said changes and prepare for similar major changes in the future, we visualized the financial market as a graph. The hypothesis was based on expertise in the financial market, and the graph was analyzed from a detailed perspective by dividing the graph into domains. We also designed an original change-detection indicator based on the structure of the graph. The results showed that the original indicator was more effective than the comparison method in terms of both the speed of response and accuracy. Explanatory change detection of this method using graphs and domains allowed investors to consider specific strategies.

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor., (© 2022. The Author(s).)

Background: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting., Methods: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model., Results: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46)., Conclusions: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting., Trial Registration: This study is registered with Clinical Trials.gov (NCT 02,551,263)., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

A new temperature measurement method-the dual two-color method-was developed to accurately measure the temperature over an ultra-wide temperature range (200-3600 °C) for ITER divertor infrared thermography. This novel method introduces a third wavelength filter to the conventional two-color method by replacing the shorter single wavelength bandpass filter with a customized dual-bandpass filter having two transmission bands, without having to add a third infrared camera. The dominant wavelength band of the total radiance through the dual-band filter changes automatically as the temperature increases and, consequently, either the shorter or longer wavelength band of the dual-bandpass filter is used to establish the two-color combination at both low and high temperatures. The dual two-color method increased the acceptable measurement error of the two-color radiance ratio for the temperature measurement requirement of the ITER divertor infrared thermography to 9.45% from that of 4.3% when using the conventional two-color method.

T-cell immunoglobulin mucin-3 (TIM-3) expressed at the T-cell surface acts as an immune checkpoint when bound by its ligand galectin-9. Blockade of immunosuppression by the TIM3/galectin-9 signalling pathway may offer novel therapeutic approaches for cancer immunotherapy. Consistent with this, TIM-3 expression is associated with poorer prognosis in several different types of cancer, possibly as a result of suppression of anticancer immunosurveillance. A number of studies have now documented some effectiveness of immune checkpoint blockade even in triple-negative breast cancer (TNBC), which is highly aggressive. However, clinical responses are relatively weak, suggesting that several different pathways may be involved. In this context, the role of the TIM-3/galectin-9 checkpoint in TNBC is not clear. The present study aimed to determine the clinicopathological significance of TIM-3 and galectin-9 expression in this cancer. To this end, 62 patients with TNBC undergoing surgery at Kansai Medical University Hospital (Hirakata, Japan), but not given neoadjuvant chemotherapy, were examined. Tissue microarrays were employed for immunohistochemistry to analyse associations of TIM-3 and galectin-9 expression and their impact on relapse-free survival relative to other poor prognostic risk factors. Galectin-9 expression was detected in 49 of 62 patient samples (79%), and TIM-3 in 30 of them (48.4%). Tumour cell galectin-9 expression was associated with a more favourable prognosis (P=0.027) as was TIM-3 expression on tumour-infiltrating lymphocytes (P=0.007). Multivariate analysis indicated that galectin-9- and TIM-3-double-positivity was significantly associated with a more favourable prognosis compared with galectin-9 and/or TIM-3 negativity (P=0.044). Thus, the TIM-3/galectin-9 signalling pathway may impact anticancer immune reactions in the tumour microenvironment of patients with TNBC. Further investigation will be necessary to determine the molecular mechanisms underlying these relationships., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yoshikawa et al.)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. The present authors recently demonstrated that expression of the lipid-related protein adipophilin (ADP) in operative specimens is a significant poor prognostic factor in patients with TNBC. Using biopsy specimens is important in making clinical decisions for patients with breast cancer; however, the prognostic significance of ADP expression in biopsy specimens from TNBC patients remains unclear. The present study determined the prognostic significance of ADP expression in biopsy specimens from TNBC patients and compared ADP-expression status between biopsy and operative specimens. The present study analyzed ADP-expression profiles in biopsy specimens from 102 patients with TNBC using immunohistochemical staining and determined relapse-free survival and risk factors associated with ADP expression in these specimens, as well as the concordance of ADP expression between biopsy and operative specimens. The results identified ADP expression in 35.3% of biopsy specimens from TNBC patients. The Ki-67 labelling index was significantly higher in ADP-positive patients (P<0.001). Univariate analysis revealed that ADP expression in biopsy specimens was significantly associated with poor relapse-free survival in patients not administered neoadjuvant chemotherapy or adjuvant chemotherapy (P=0.026). Furthermore, the concordance rate of ADP expression between biopsy and operative specimens was 73.1%, with a Cohen's kappa coefficient of 0.385 (P=0.003). These findings suggested that ADP expression in biopsy specimens might be a useful prognostic marker for patients with TNBC and could potentially provide important information regarding treatment strategies for these patients., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yoshikawa et al.)

It is well known that cancer cells produce energy via anaerobic glycolysis. Lipid metabolism is often upregulated in numerous types of cancer. Our previous study demonstrated that adipophilin (ADP), a lipid-associated protein, was a poor prognostic indicator in patients with triple-negative breast cancer (TNBC). However, the mechanism of ADP expression in TNBC remains unclear. Fatty acid synthase (FASN) is a crucial enzyme in de novo fatty acid synthesis, and its upregulation has been reported in several types of carcinomas; however, to the best of our knowledge, the association of FASN and ADP in TNBC remains unclear. The present study analysed the association between FASN and ADP expression and the prognostic significance of FASN in TNBC. Using immunohistochemical methods and tissue microarrays, the present study examined FASN expression in 61 patients with TNBC. Overall and relapse-free survival and their risk factors were analysed for FASN expression and compared with ADP expression. A total of 40 (65.6%) patients were classified as FASN-high (score ≥120), and this was significantly associated with a lower Ki-67 labelling index (P=0.011). FASN expression was not associated with relapse-free survival and overall survival. FASN-high was negatively associated with ADP expression (P=0.041). The results of the present study revealed that FASN-high was associated with a lack of ADP expression and a lower Ki-67 labelling index. These results indicated that de novo fatty acid synthesis by FASN is not the main pathway of lipogenesis and the source of energy in cancer cells of ADP-positive highly proliferative TNBC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yoshikawa et al.)

Background: This study aimed to clarify the factors for efficient procedures (EP) in superficial femoral artery (SFA) chronic total occlusion (CTO)., Methods: We retrospectively analyzed 200 consecutive limbs that underwent treatment for SFA CTO. The patients were divided into three groups according to the main strategies: subintimal angioplasty (SIA) (n = 123), Crosser use (n = 50), and 0.014″ CTO guidewire (CTO-GW) (n = 27). To determine the factors for an EP (EP; contrast volume <130 mL and procedure time <20 min; derived from non-CTO [control] procedures), the variables (P < 0.2) underwent multivariate analysis., Results: SIA included more Trans-Atlantic Inter-Society Consensus C/D lesions and contralateral femoral approaches, and additional GW use (P < 0.05). CTO-GW presented a shorter occlusion length and elapsed time, and used less retrograde approach than the other strategies (P < 0.05). Crossers had a higher incidence of perforation (P = 0.002). The prompt retrograde approach had a similar actual retrograde procedure time, but a shorter total procedure time, compared to that of the delayed adoption (P < 0.001). EP was achieved in 14 limbs (7.0%). Multivariate analysis revealed that occlusion length (adjusted odds ratio [OR], 0.89; 95% CI, 0.81-0.96; P = 0.004) and SIA (OR, 8.71; 95% CI, 1.32-175.27; P = 0.02) were associated with EP., Conclusions: SIA contributed to EP. The timing of the retrograde approach was crucial because its delay resulted in an excessive procedure time., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Solid papillary carcinoma (SPC) is a rare but distinct clinicopathological feature of breast cancer characterised by frequent neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a useful neuroendocrine marker for various neuroendocrine tumours. α-thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) are useful prognostic markers for patients with pancreatic neuroendocrine tumours. However, to the best of our knowledge, few studies have addressed INSM1 expression in SPCs. Although ATRX, DAXX and δ-like canonical notch ligand 3 (DLL3) are frequently expressed in neuroendocrine lung carcinomas, there are no reports on their expression in SPCs. Therefore, the present study aimed to analyse the expression profiles of INSM1, ATRX, DAXX and DLL3 in the largest series of patients with SPC that has been, to the best of our knowledge, studied until now. Immunohistochemical analyses were performed to determine chromogranin A, synaptophysin, INSM1, ATRX, DAXX and DLL3 expression in 39 specimens surgically resected from patients with SPC (18 SPC in situ and 21 SPC invasive). The associations between the expression of these markers and the clinicopathological factors were investigated. Chromogranin A, synaptophysin and INSM1 were expressed in 64.1, 100 and 92.3% of the patients, respectively. Both ATRX and DAXX expression was observed in 28.2% of the patients. No patient expressed DLL3. Lack of INSM1 or chromogranin A expression was significantly associated with advanced pathological stages in patients with SPC (P=0.033) and in patients with invasive SPC (P=0.012), showing a tendency for a high Ki-67 labelling index (LI) and advanced histological grade in patients with invasive SPC. Loss of ATRX or DAXX expression was significantly associated with lymphatic invasion, but not with histological grade, Ki-67 LI or presence of invasive tumours. Thus, INSM1 was demonstrated to be a useful diagnostic marker for SPCs. Overall, detecting the lack of INSM1 or chromogranin A expression may be useful for analysing the characteristics of tumour cells in SPCs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yanai et al.)

Aim: To assess the impact of breast-cancer treatment on fertility., Methods: We conducted a retrospective, case-based survey of treatments administered for infertility and pregnancy outcomes after patients underwent treatment for breast cancer. Surveys were distributed to breast oncology facilities and reproductive endocrinology and infertility (REI) facilities., Results: As high as 60% of the pregnancies in women under the age of 35 years occurred spontaneously. Additionally, the fertility rates decreased as age increased (under 35 years of age: 40%, 35-39 years of age: 21%, 40-44 years of age: 10%, respectively). In women who became pregnant after treatment for breast cancer, conception was achieved within 1 to 3 years after beginning to try for pregnancy., Conclusions: After treatment for breast cancer, women can expect spontaneous pregnancy, especially if they are under 35 years of age. It is important for patients 35 years of age and older to commence assisted reproductive technology in a timely manner when pursuing fertility after treatment for breast cancer., (© 2021 Japan Society of Obstetrics and Gynecology.)

Recurrent Clostridioides difficile infection (rCDI) is a frustrating condition that may affect a person's quality of life for months. Microbiome-based therapy such as fecal microbiota transplantation (FMT) has been effective for the treatment of rCDI by correcting the imbalance of the gut microbiota. Appropriate antibiotic treatment is recommended for at least two recurrences before offering FMT. Here, we report the case of a 92-year-old woman who experienced five recurrences of Clostridioides difficile infection (CDI) (six episodes in total) complicated by dementia and delirium, both of which were dramatically improved by FMT, which was associated with alterations in fecal microbiota and the metabolome. Analyses of whole microbial communities and metabolomic analyses were performed on stool specimens collected from the patient on the first episode, the third episode, the day of FMT (before FMT), and 2, 8, and 23 weeks after the FMT and from the donor. The patient had various fecal dysbioses on the first and third episodes and on the day of FMT. Two weeks after FMT, diversity of the gut bacteriome as well as the virome increased dramatically and was reflected in a positive clinical outcome for this patient. Metabolomic analysis revealed that short-chain fatty acids, which have been reported to be associated with improved memory function, were increased after FMT., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The successful intervention for peripheral artery disease is limited by complex chronic total occlusions (CTOs). During CTO wiring, without the use of intravascular or extravascular ultrasound, the guidewire position is unclear, except for calcified lesions showing the vessel path. To solve this problem, we propose a novel guidewire crossing with plaque modification method for complex occlusive lesions, named the "Direct tip Injection in Occlusive Lesions (DIOL)" fashion., Main Text: The "DIOL" fashion utilizes the hydraulic pressure of tip injection with a general contrast media through a microcatheter or an over-the-wire balloon catheter within CTOs. The purposes of this technique are 1) to visualize the "vessel road" of the occlusion from expanding a microchannel, subintimal, intramedial, and periadventitial space with contrast agent and 2) to modify plaques within CTO to advance CTO devices safely and easily. This technique creates dissections by hydraulic pressure. Antegrade-DIOL may create dissections which extend to and compress a distal lumen, especially in below-the-knee arteries. A gentle tip injection with smaller contrast volume (1-2 ml) should be used to confirm the tip position which is inside or outside of a vessel. On the other hand, retrograde-DIOL is used with a forceful tip injection of moderate contrast volume up to 5-ml to visualize vessel tracks and to modify the plaques to facilitate the crossing of CTO devices. Case-1 involved a severe claudicant due to right superficial femoral artery occlusion. After the conventional bidirectional subintimal procedure failed, we performed two times of retrograde-DIOL fashion, and the bidirectional subintimal planes were successfully connected. After two stents implantation, a sufficient flow was achieved without complications and restenosis for two years. Case-2 involved multiple wounds in the heel due to ischemia caused by posterior tibial arterial occlusion. After the conventional bidirectional approach failed, retrograde-DIOL was performed and retrograde guidewire successfully crossed the CTO, and direct blood flow to the wounds was obtained after balloon angioplasty. The wounds heeled four months after the procedure without reintervention., Conclusions: The DIOL fashion is a useful and effective method to facilitate CTO treatment., (© 2021. The Author(s).)

Background: Vascular calcification is a predictor of poor clinical outcome during and after endovascular intervention. Guidewire crossing techniques and devices have been developed, but chronic total occlusions (CTOs) with severe calcification often prevent subintimal re-entry. We propose a novel guidewire crossing approach combined needle rendezvous with balloon snare technique, named the "needle re-entry" technique, for treatment of complex occlusive lesions., Main Text: A 73-year-old female with severe claudication in her right calf with ankle brachial index of 0.62, and a computed tomography angiogram showed a long occlusion with diffuse calcification in superficial femoral artery. She was referred to our department to have peripheral interventions. Since the calcified vascular wall of the lesion prevented the successful re-entry, the "needle re-entry" was performed. First, a retrograde puncture of the SFA, distally to the occlusion, was performed and an 0.018-in. guidewire with a microcatheter was inserted to establish a retrograde fashion. Second, an antegrade 5.0-mm balloon was advanced into a subintimal plane and balloon dilation at 6 atm was maintained. Third, an 18-gauge needle was antegradely inserted from distal thigh to the dilated 5.0-mm balloon. After confirming a balloon rupture by the needle penetration, we continued to insert the needle to meet the retrograde guidewire tip. Then, a retrograde 0.014-in. guidewire was carefully advanced into the needle hole, named the "needle rendezvous" technique. After further guidewire advancement to accomplish a guidewire externalization, the needle was removed. Finally, since the guidewire was passing through the 5.0-mm ruptured balloon, the balloon was withdrawn, and the guidewire was caught with the balloon and successfully advanced into the antegrade subintimal space, named the "balloon snare" technique. After the guidewire was advanced into the antegrade guiding sheath and achieved a guidewire externalization, an endovascular stent graft and an interwoven stent were deployed to cover the lesion. After postballoon dilation, an angiography showed a satisfactory result without complications. No restenosis, reintervention, and limb loss have been observed for one year follow-up period after this technique., Conclusions: The "needle re-entry" technique is a useful guidewire crossing technique to revascularize femoropopliteal complex CTOs with severe calcification which prevent the achievement of guidewire crossing with the conventional procedures., (© 2021. The Author(s).)

Objective: Coil embolization (CE) for coronary artery perforation (CAP) has not been thoroughly evaluated. This study aimed to evaluate the extent of myocardial damage and impact on cardiac function after CE for CAP., Methods: A total of 110 consecutive patients treated with CE for CAP were retrospectively identified. The degree of myocardial damage and impact on cardiac function were evaluated., Results: Forty-nine (44.5%) cases involved chronic total occlusions. A guidewire was the cause of perforation in 97 (88.2%) patients. The success rate of CE was 98.2%. Almost all patients were prescribed either antiplatelet drugs or anticoagulant medication or both. Patients with perforation types III and IV were found to be prone to creatinine kinase (CK) elevation and epicardial main vessel perforation, thereby causing myocardial damage. No changes were noted in the ejection fraction (EF) in patients with type V distal perforation and collateral channel perforation, while patients with perforation of the epicardial main vessel may show impaired cardiac function afterward., Conclusions: CE is safe and effective for treating CAP, especially when collateral channels and distal vessels are involved. Meanwhile, efforts should be taken to prevent CAP in epicardial main vessels since it may be difficult to treat with CS and cause myocardial damage when bailed out with CE leading to vessel sacrifice. We found that it was not necessary to change the anticoagulant regimen after CE owing to its ability to achieve robust hemostasis., Competing Interests: The authors report no financial relationships or conflicts of interest regarding the content herein., (Copyright © 2021 Daisuke Hachinohe et al.)

Background: Percutaneous coronary intervention (PCI) in hemodialysis patients with severely calcified and diffused lesions is associated with extremely high rates of major adverse cardiovascular events (MACE), even when facilitated by rotational atherectomy (ROTA). Potential risk factors for MACE with ROTA-facilitated PCI in hemodialysis patients should be identified., Methods: We retrospectively analyzed a consecutive cohort of patients from the Sapporo Cardiovascular Clinic database, who were on maintenance hemodialysis with severe calcified lesions and treated with ROTA-facilitated PCI. Clinical and interventional procedure characteristics were collected and compared between patients with and without MACE, defined as all-cause death, hospitalization due to heart failure, definite stent thrombosis, or target lesion revascularization (TLR) at 1-year follow-up. The individual outcomes of MACE and TLR in the cohort were presented as Kaplan-Meier percentages. Cox regression analyses were performed to identify independent predictors of MACE., Results: A total of 138 patients undergoing hemodialysis and followed up for 362.50 (243.75, 382.25) days. Sixty-one patients in the cohort had MACE, most of which were TLR (47.5%, 29/61). Cumulative all-cause death at 30-day and 1-year follow-up were 6.52% and 18.8%, respectively. Patients with right coronary artery (RCA) lesions, in-stent restenosis (ISR) lesions, and were more likely to have MACE, even with larger reference vessel diameter and greater acute gain after PCI. Cox regression analysis demonstrated that ISR lesion was positively associated with both MACE (HR 3.21, 95% CI: 1.59-6.48) and TLR (HR 5.08, 95% CI: 1.78-14.47), latter of which was also proved to be significantly related to greater acute gain (HR 1.95, 95% CI: 1.12-3.39). In subgroup analysis, RCA was found to be positively associated with MACE in de novo lesion (HR 2.83, 95% CI: 1.28-6.28)., Conclusions: We found that the overall prognosis of ROTA-facilitated PCI in hemodialysis patients was poor. ISR was a significant risk factor for MACE, especially TLR.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. A recent study demonstrated the efficacy of anti-PD-L1 (anti-programmed death ligand-1) immunotherapy in patients with TNBC. However, the identification of TNBC patients who may benefit from immunotherapy is a critical issue. Several assays have been used to evaluate PD-L1 expression, and a few studies comparing PD-L1 expression using various primary antibodies in TNBC tissues have been reported. However, the expression profiles of the PD-L1 using the 73-10 assay have not yet been analyzed in TNBC tissues., Methods: We analyzed the PD-L1 immunohistochemical profiles of 62 women with TNBC using the 73-10, SP142 (companion diagnostic for atezolizumab), and E1L3N assays. PD-L1 expression on immune cells (ICs) and tumor cells (TCs) was also evaluated, and PD-L1 positivity was defined as a PD-L1-expressing ICs or TCs ≥ 1%., Results: The expression rates of PD-L1 were 79.0%, 67.7%, and 46.8% on ICs, and 17.7%, 6.5%, and 12.9% on TCs using the 73-10, SP142, and E1L3N assays, respectively. The concordance rates between the 73-10 and SP142 assays were 85.5% (on ICs) and 88.7% (on TCs), respectively, and substantial agreement on ICs (coefficient 0.634) and moderate agreement (coefficient 0.485) on TCs were noted. Sample age and tumor diameter did not influence the ratio of PD-L1 expression among the assays., Conclusions: The positive rate on ICs and TCs of the 73-10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73-10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy., Competing Interests: The authors have declared that no competing interests exist.

Ocean warming and the associated changes in fish herbivory have caused polarward distributional shifts in the majority of canopy-forming macroalgae that are dominant in temperate Japan, but have little effect on the alga Sargassum fusiforme . The regeneration ability of new shoots from holdfasts in this species may be advantageous in highly grazed environments. However, little is known about the factors regulating this in Sargassum species. Moreover, holdfast tolerance to high-temperature and nutrient-poor conditions during summer has rarely been evaluated. In the present study, S. fusiforme holdfast responses to the combined effects of temperature and nutrient availability were compared to those of sexually reproduced propagules. The combined effects of holdfast fragmentation and irradiance on regeneration were also evaluated. Propagule growth rate values changed from positive to negative under the combination of elevated temperature (20 °C-30 °C) and reduced nutrient availability, whereas holdfasts exhibited a positive growth rate even at 32 °C in nutrient-poor conditions. The regeneration rate increased with holdfast fragmentation (1 mm segments), but was unaffected by decreased irradiance. These results suggest that S. fusiforme holdfasts have a higher tolerance to high-temperature and nutrient-poor conditions during summer than propagules, and regenerate new shoots even if 1-mm segments remain in shaded refuges for fish herbivory avoidance.