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Background: The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective cohort study, we determined the performance of the OSNA assay in DCIS and the pathogenesis of node-positive DCIS.Methods: The subjects consisted of 623 patients with DCIS who underwent sentinel lymph node (SN) biopsy. Of these, 2-mm-sectioned nodes were examined using frozen-section (FS) histology in 338 patients between 2007 and 2009, while 285 underwent OSNA whole node assays between 2009 and 2011. The SN-positivity rate was compared between cohorts, and the characteristics of OSNA-positive DCIS were investigated.Results: The OSNA detected more cases of SN metastases than FS histology (12 out of 285, 4.2% vs 1 out of 338, 0.3%). Most of the metastases were micrometastases. The characteristics of high-risk DCIS (i.e., mass formation, size, grade, and comedo) and preoperative breast biopsy (i.e., methods or time to surgery) were not valid for OSNA assay–positive DCIS.Conclusion: The OSNA detects more SN metastases in DCIS than FS histology. Further examination of the primary tumours and follow-up of node-positive DCIS are needed to elucidate the pathogenesis. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity within individual breast tumors is a well-known phenomenon that may contribute to drug resistance. This heterogeneity is dependent on several factors, such as types of oncogenic drivers and tumor precursor cells. The purpose of our study was to engineer a mouse mammary tumor model with intratumoral heterogeneity by using defined genetic perturbations. To achieve this, we used mice with knockout (-/-) of Ink4a/Arf, a tumor suppressor locus; these mice are known to be susceptible to non-mammary tumors such as fibrosarcoma. To induce mammary tumors, we retrovirally introduced an oncogene, HRAS(G12V), into Ink4a/Arf−/− mammary cells in vitro, and those cells were inoculated into syngeneic mice mammary fat pads. We observed 100% tumorigenesis. The tumors formed were negative for estrogen receptor, progesterone receptor and HER2. Further, they had pathological features similar to those of human triple-negative breast cancer (TNBC) (for example, pushing borders, central necrosis). The tumors were found to be heterogeneous and included two subpopulations: CD49f− quiescent cells and CD49f+cells. Contrary to our expectation, CD49f− quiescent cells had high tumor-initiating potential and CD49f+cells had relatively low tumor-initiating potential. Gene expression analysis revealed that CD49f− quiescent cells overexpressed epithelial-to-mesenchymal transition-driving genes, reminiscent of tumor-initiating cells and claudin-low breast cancer. Our animal model with intratumoral heterogeneity, derived from defined genetic perturbations, allows us to test novel molecular targeted drugs in a setting that mimics the intratumoral heterogeneity of human TNBC. [ABSTRACT FROM AUTHOR]

Background:For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy.Methods:In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes.Results:The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively.Conclusion:The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present. [ABSTRACT FROM AUTHOR]

Background: The one-step nucleic acid amplification (OSNA) assay is a molecular-based lymph-node metastasis detection procedure that can assess a whole node and yields semi-quantitative results for the detection of clinically relevant nodal metastases. We aimed to determine the performance of the OSNA assay as an accurate nodal staging tool in comparison with routine histological examination.Methods: Subjects comprised 183 consecutive patients with pT1-2 breast cancer who underwent axillary dissection after positive sentinel-node (SN) biopsy with the OSNA assay. Of these, for non-SN evaluation, 119 patients underwent OSNA assay evaluation, whereas 64 had single-section histology. We compared the detection rates of non-SN metastasis and upstaging rates from the SN stage according to the American Joint Committee on Cancer staging between the OSNA and histology cohorts.Results: OSNA detected more cases of non-SN metastases than histology (OSNA 66/119, 55.5% vs histology 13/64, 20.3%; P<0.001), particularly micrometastases (36/119, 30.3% vs 1/64, 1.6%; P<0.001). Total upstaging rates were similar in both cohorts (20/119, 16.8% vs 9/64, 14.1%, P=0.79).Conclusion: OSNA detects a far greater proportion of non-SN micrometastases than routine histological examination. However, upstaging rates after axillary dissection were not significantly different between both cohorts. Follow-up of the OSNA cohort is required to determine its clinical relevance. [ABSTRACT FROM AUTHOR]

We examined the validity of the St Gallen algorithm for Japanese breast cancer patients and sought the optimal indications of endocrine monotherapy as adjuvant systemic treatment. According to the 2005 St Gallen algorithm, endocrine responsiveness (responsive, uncertain, or non-responsive) and recurrence risk (low, intermediate, or high) were assessed in 436 invasive breast cancer patients, who underwent surgery and adjuvant therapy of tamoxifen alone in 1982–1993. Furthermore, intermediate-risk patients were divided into three groups based on lymph node metastasis and number of risk factors as follows: Group A, negative lymph node metastasis and one risk factor; Group B, negative lymph node metastasis and two to five risk factors; and Group C, positive lymph node metastasis. Cumulative 10-year recurrence-free survival (RFS) rates of each type were calculated. Recurrence-free survival was as follows: endocrine responsiveness; responsive: 86.0%, uncertain: 79.5%, non-responsive: 72.4%, risk category; low: 93.3%, intermediate: 84.0%, high: 59.6%, intermediate-risk patients; Group A: 93.5%, Group B: 88.2%, and Group C: 75.0%. In conclusion, patient classification based on St Gallen algorithm appears valid in Japanese breast cancer patients. Endocrine monotherapy may be sufficient as adjuvant treatment in the intermediate-risk patients, in which only one risk factor was present without any metastatic involvement in lymph node.British Journal of Cancer (2007) 97, 654–658. doi:10.1038/sj.bjc.6603916 www.bjcancer.com Published online 28 August 2007 [ABSTRACT FROM AUTHOR]

Abstract Background Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance. Results Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR. Conclusion These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.

Abstract Background The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate. Methods We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size. Results Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001). Conclusions Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.

Abstract Background The impact of skin invasion in node negative breast cancer is uncertain. Methods We determined the prognosis in 97 node negative breast cancer patients (case group) who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period. Results Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032). Conclusion Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

Background: The OSNA (One Step Nucleic acid Amplification) assay is a semi-automated lymph node examination method using molecular biological technique. The OSNA assay has been validated for breast cancer patients without receiving preoperative systemic therapy (PST) by several clinical studies and has currently become more popular as sentinel lymph node (SLN) examination method with the following two main advantages; 1) to allow examination of the whole portion of a node, 2) to allow intraoperative judgment of metastasis positive or negative. However, the feasibility of the OSNA assay in breast cancer patients treated by PST has never been confirmed. In this multi-central clinical study, we compared the judgments of the OSNA assay and of pathological examination on lymph nodes dissected after receiving PST to evaluate the performance of the OSNA assay. Material & Methods: Three hundred two nodes dissected from the 80 breast cancer patients who received PST were examined. Each lymph node was divided at 2mm intervals and the slices were alternately applied to the OSNA assay and pathological examination with H&E staining and CK19 immunohistochemical staining of permanent-section. In pathological examination, judgments of metastasis positive or negative were determined by one central-review pathologist according to the criteria of AJCC 7th edition ("positive" if >0.2mm metastases were detected). Result: The overall concordance rate between the OSNA assay and pathological examination was 91.1% (275/302) with sensitivity of 88.3% (53/60) and specificity of 91.7% (222/242) (Table). These results are very similar to those of the Japanese clinical validation study in breast cancer patients without receiving PST which was conducted by the almost same protocol (Tamaki Y, et al. Clin Cancer Res, 2009, 15: 2879-2884). Conclusion & Discussion: These results indicate the OSNA assay can be applicable for breast cancer patients after receiving PST as well as breast cancer patients without receiving PST. The OSNA assay will enable to examine the whole portion of nodes, leading to more detection of metastases (especially micrometastases) and more exact nodal staging for breast cancer patients treated by PST. Also, for the patients who receive sentinel lymph node biopsy after PST, the OSNA assay will be useful as intraoperative examination method of SLNs because it is expected to provide more correct judgments than current intraoperative methods such as frozen-section or touch-print cytology. [ABSTRACT FROM AUTHOR]

Background: The standardized assessment of Ki-67 labeling index (LI) plays pivotal roles in identifying the patients (pts) with primary breast cancer who could benefit from systemic chemotherapy, in particular among pts with estrogen receptor(ER)-positive cancers. Therefore, in this study, we evaluated the inter-observer concordance of the assessment of Ki-67 LI in archival materials. Methods: Six surgical pathologists specializing in breast pathology from different Japanese institutions participated in this study. All slides were prepared from archival tissues of breast cancer fixed in 10% buffered formalin for 24 hours in a single institution (KU). Three independent studies were conducted. Study 1) Six consecutive slides were prepared from 5 cases. A slide from each case was stained with MIB-1 (DAKO, Denmark) in each institution according to their routine methods. Total of 30 stained slides were assessed for Ki-67 LI by each pathologist using two different modes of assessment. One is the scoring system in which the rate of positive cells was scored from 1 (0-9 %) to 10 (90-100%) without counting the cell number. The second one is the counting system in which approximately 1000 cells in total were counted in the hot spots and the positive rate was calculated. Study 2) Twenty tumors with Ki-67 LI ranging from 5 to 25 (15 ± 10) %, stained in a single institution (KU) were assessed by each pathologist by the counting system. Study 3) In order to avoid variations by assessment in varied microscopic fields and to further evaluate the variation of threshold of immunointensity interpreted as positive by different pathologists, fifteen printed photographs of Ki-67-stained slides were sent and assessed for Ki-67 LI by each participating breast pathologist. Results: Study 1) The counting system demonstrated a better correlation of Ki-67 LI among six pathologists than the scoring system {the intraclass correlation coefficient (ICC), 0.66 (95% confidence interval 0.52-0.78) for the counting system, 0.57 (0.42-0.72) for the scoring system}. The two assessment systems showed a moderate correlation {ICC, 0.68 (0.60-0.75)}. Study 2) The assessment of Ki-67 LI in 20 slides with Ki-67 LI of 5 to 25 % demonstrated a correlation similar to that in the specimens with an unrestricted range of Ki-67 LI in the study 1 {ICC, 0.68 (0.50-0.81) for the study 2, 0.66 (0.52-0.78) for the study 1}. Study 3) The assessment of Ki-67 LI in the same photographs yielded a considerably significant concordance among six pathologists {ICC, 0.94 (0.88-0.97)}. Conclusion: The counting system turned out better than the scoring system in terms of the inter-observer agreement of the Ki-67 LI assessment. The degree of concordance was by no means influenced by the range of Ki-67 LI. The concordance of the Ki-67 LI assessment among six participating pathologists was significantly high when the assessed field was fixed using the same photographs for evaluation, suggesting that the selection of the fields for evaluation is critical. These results suggest that identification of hot spots for evaluation is pivotal for obtaining the accurate Ki-67 LI of breast cancer and still images of these hot spots could provide reproducible results. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the concordance of human epidermal growth factor receptor 2 (HER2) expression scoring by immunohistochemistry (IHC) among practicing pathologists in Japan, given the challenging nature of scoring and the critical role of HER2 status in breast cancer management., Methods: Whole slide images (WSI) from 20 invasive breast cancer cases (1 representative WSI per case) selected to represent a diverse IHC scores and staining patterns were used in an online survey involving seven reference pathologists who established consensus HER2 IHC scores (0 to 3 +) decided by majority interpretation. Participating pathologists nationwide scored the same 20 WSI cases online using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guidelines. Deidentified case metadata were registered in the uPath system., Results: A total of 144 participating pathologists responded. The scoring results of the participating pathologists most commonly agreed with the consensus IHC score, followed by a ± 1 point deviation and no survey responses with > 1 point deviation. The mean percentage of agreement with the consensus score for all 20 cases was 63.4%. In cases where the reference pathologists' scores were discordant, the participating pathologists also showed a lower concordance rate., Conclusion: This study highlighted the current status of HER2 expression scoring by IHC for breast cancer among pathologists in Japan. These findings underscore the challenges in HER2 IHC scoring cases and emphasize the need for improved standardization and training, especially in the evolving landscape of HER2-targeted therapies., (© 2024. The Author(s).)

Although thin-film composite membranes have achieved great success in CO 2 separation, further improvements in the CO 2 permeance are required to reduce the size and cost of the CO 2 separation process. Herein, we report the fabrication of composite membranes with high CO 2 permeability using a laser-patterned porous membrane as the support membrane. High-aspect-ratio micropatterns with well-defined micropores on their surface were carved on microporous polymer supports by a direct laser writing process using a short-pulsed laser. By using a Galvano scanner and optimizing the laser conditions and target materials, in-plane micropatterns, such as microhole arrays, microline grating, microlattices, and out-of-plane hierarchical micropatterns, were created on porous membranes. An aqueous suspension of hydrogel microparticles doped with an amine-based mobile carrier was sprayed onto the patterned surface to form a defect-free thin separation layer. The surface area of the separation layer on the patterned support is up to 80% larger than that of flat pristine membranes, resulting in a 52% higher CO 2 permeance (1106 GPU) with a CO 2 /N 2 selectivity of 172. The laser-patterned porous membranes allow the development of inexpensive and high-performance functional membranes not only for CO 2 separation but also for other applications, such as water treatment, cell culture, micro-TAS, and membrane reactors.

The Japanese Breast Cancer Society Clinical Practice Guidelines are published as timely guidance on clinical issues in breast cancer treatment in Japan. In the recent edition of these guidelines, we addressed a new clinical question 34 (CQ 34, systemic treatment part) "Is trastuzumab deruxtecan recommended for patients with unresectable or metastatic HER2-low breast cancer?" and a new future research question 7 (FRQ 7, pathological diagnosis part) "How is HER2-low breast cancer diagnosed for the indication of trastuzumab deruxtecan?". These questions address use of trastuzumab deruxtecan in patients with unresectable or metastatic HER2-low breast cancer who have previously received chemotherapy for metastatic disease. The strengths of evidence and recommendation were determined through a quantitative and qualitative systematic review using multiple outcomes, including efficacy and safety. We conclude that trastuzumab deruxtecan is recommended for this patient population (strength of recommendation: 1; strength of evidence: moderate; CQ34) and that HER2-low expression for the indication of trastuzumab deruxtecan should be diagnosed using companion diagnostics based on appropriate criteria (FRQ7)., (© 2024. The Author(s).)

Background: Temozolomide (TMZ) is an alkylating agent used to treat glioblastoma. However, the pharmacokinetics of TMZ to establish a treatment strategy for patients undergoing hemodialysis (HD) remain unclear. In this case report, we evaluated the pharmacokinetics and HD removal rate of TMZ in a patient with glioblastoma undergoing HD to determine optimal dosing of TMZ., Methods: A 78-year-old man with glioblastoma who underwent HD 3 times a week was treated with TMZ concomitant with radiotherapy. One dose of TMZ was prescribed at 75 mg/m 2 on the day before HD and another dose of 37.5 mg/m 2 on the day before non-HD. Peak and trough concentrations (1 hour and 12 hours after dosing, respectively) were evaluated before HD and on non-HD days. HD removal rate of TMZ was calculated based on the predialyzer and postdialyzer plasma concentrations. Furthermore, the TMZ plasma concentrations were measured using liquid chromatography-tandem mass spectrometry., Results: The mean plasma peak and trough concentrations ± SD after 75 mg/m 2 TMZ were 2917 ± 914 and 108 ± 17.6 ng/mL, respectively. Those after 37.5 mg/m 2 TMZ dosage were 1305 ± 650 and 53.8 ± 11.8 ng/mL, respectively. The mean HD TMZ removal rate was 84.9 ± 1.9%., Conclusions: TMZ was tolerable in patients undergoing HD. Based on the data from a single individual pharmacokinetic perspective, the pharmacokinetics of TMZ in this patient undergoing HD were comparable with those observed in patients with normal renal function. In addition, it may be reasonable to administer TMZ after HD because of the high HD removal rate., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: An exchange maneuver is useful for the delivery of devices to target vessels. However, hemorrhagic complications can occur due to vessel perforation during an exchange maneuver. In addition, the exchange is often challenging due to unfavorable anatomy. Center Wire is an exchange-length wire with a nondetachable stent that was developed to improve navigation and stability during exchange maneuvers. The aim of this study is to investigate the safety and efficacy of Center Wire of the anchor wire technique during neuroendovascular treatment., Methods: Ten patients with intracranial aneurysms were treated after signing a Certified Review Board-approved consent. Anchor wire technique was used in all patients to navigate catheters to the target vessel for aneurysm treatment., Results: Anchor wire technique was successfully applied in all 10 cases using Center Wire. One device-related incident of vasospasm occurred which was asymptomatic. No device-related dissection, perforation, or thromboembolic events occurred. One patient had intraoperative aneurysm rupture during coil placement which was treated immediately without clinical consequences. Two patients had postoperative ischemic strokes due to thrombotic occlusion of branches originating from the aneurysm which were unrelated to the device., Conclusions: This first-in-human trial of Center Wire demonstrated the safety and efficacy of the anchor wire technique for neuroendovascular treatment in a strictly regulated prospective registry trial.

Background: ER+HER2+ breast cancer requires most types of systemic therapies perioperatively. However, treatment resistance is often experienced. The current study investigated the predictive and prognostic value of intratumoral heterogeneity and conventional clinicopathological factors in patients with ER+HER2+ breast cancer., Methods: This research included two patient cohorts with ER+HER2+ breast cancer. Cohort A included patients who underwent surgery without neoadjuvant chemotherapy (NAC). Cohort B comprised patients who received NAC followed by surgery. Intratumoral heterogeneity was assessed via ER and HER2 double staining, and the number of cells stained with different patterns of ER and HER2 was counted., Results: In total, 11 of 92 tumors in cohort A and four of 45 tumors in cohort B consisted exclusively of double-positive (ER+ and HER2+) cells (homogeneous). The rest had different combinations of cells (heterogeneous). The pathological complete response (pCR) rates differed based on tumoral cell components but not intratumoral heterogeneity. The pCR rate of tumors with ER-HER2+ cells but without HER2- cells was higher than that of others (45.5% vs 4.3%; p = 0.0013). Low ER and PgR Allred scores indicated better pCR rates than high scores (p = 0.0005 and 0.024, respectively). Multivariate analysis showed that the ER Allred score and cell component of ER-HER2+ cells without HER2- cells were independent predictors of pCR (p = 0.0055 and 0.0081, respectively). In cohort B, posttreatment Ki67, but not pCR, was a prognostic factor of DFS and OS (p = 0.028 and 0.017, respectively). The prognostic value of combined posttreatment Ki67 and pCR was superior to that of either alone. Combined pCR and posttreatment Ki67 had an independent prognostic value for DFS and OS (p = 0.0068 and 0.0101, respectively)., Conclusions: In ER+HER2+ breast cancer, the presence of ER-HER2+ cells without HER2- cells was independently associated with pCR. Combined posttreatment Ki67 and pCR can be more precise in predicting prognosis than pCR alone., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Flow diverter or stent implantation to intracranial target lesion requires large inner diameter microcatheter navigation. The exchange method using stiff long wire is often necessary if it is difficult to navigate over the regular guidewire. However, this method has an intrinsic risk of vessel damage and may cause severe complications. We investigated the safety and efficacy of a new device, the Stabilizer device for navigation in a first-in-human clinical trial under the Certified Review Board agreement., Materials and Methods: The Stabilizer is a 320 cm length exchange wire with a stent for anchoring and is compatible with a 0.0165" microcatheter. The trial design is a prospective single-arm open-label registry. Inclusion criteria are elective flow diverter treatment or stent-assisted coiling, expected to be difficult to navigate a microcatheter with a regular micro guidewire, and obtained documented consent. The primary endpoint of the study was a hemorrhagic complication., Results: Five patients were enrolled in this trial. The median age is 52 years, ranges from 41 to 70, and all patients were female. Three aneurysms were located on the internal carotid artery, one on the vertebral artery, and one on the basilar artery. Basilar artery aneurysm was treated by stent-assisted coiling and others were treated by flow diverter deployment. All cases successfully navigate microcatheter for the treatment by the trial method using Stabilizer device without any adverse event., Conclusions: The results from this first-in-human consecutive five cases show the safety of the Stabilizer device in neuro-endovascular therapy for navigation of devices to the intracranial target lesion., Competing Interests: The authors declare the following conflict of interests: This trial received trial devices from Bolt Medical, without specific grant. Grant from Kobe City Medical Center General Hospital support this trial. The authors, NS, NK and ST, were consultants of Bolt Medical at the treatment, but declare that this trial was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. 10.13039/100007057NS received a research grant from Biomedical Solutions, 10.13039/501100002973Daiichi-Sankyo, and Terumo; lecturer's fees from Asahi-Intec, Biomedical Solutions, 10.13039/501100002973Daiichi-Sankyo, and Medtronic; membership on the advisory boards for Johnson&Johnson, 10.13039/100004374Medtronic and 10.13039/501100008645Terumo without related this manuscript. HI received lecturer's fee from 10.13039/100004374Medtronic. NK has been a consultant for Stryker and Medtronic. 10.13039/501100004347ST received research funds from Biomedical Solutions, Rapid Medical and Medtronic, and a consultant for TG Medical, 10.13039/100008476Irvine Neurovascular, Balt USA, Cerenovus, 10.13039/100004374Medtronic, Phenox GmbH, MicroVention, Kaneka USA, Century Medical Inc., EnCompass, NVMedTech, and 10.13039/100008894Stryker. The other authors have no personal or financial interest in any of the materials or devices described in this article., (© 2023 The Author(s).)

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two-dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging-based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near-infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label-free MPM imaging is a promising method for the real-time automatic diagnosis of breast cancer., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6 mm; median neck width, 6.3 mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (< 10 mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥ 10 mm) aneurysms (P = .024). The median clinical follow-up was 22 months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vasospasm, initial neurological damage, rebleeding, and periprocedural complications are associated prognostic factors for clinical outcomes after aneurysmal subarachnoid hemorrhage (SAH). In this study, factors related to delayed ischemic neurological deficit (DIND) are evaluated using data from our institute for the last 18 years. Data from 2001 to 2018 of patients with aneurysmal SAH who underwent surgical clipping (SC) or endovascular coiling (EC) within 7 days of onset were retrospectively analyzed. Cases of mortality within 5 days after treatment were excluded. Multivariate analysis was used to identify the risk factors for DIND. In total, 840 cases of SAH were assessed; among these cases, 384 (45.7%) and 456 (54.3%) were treated with SC and EC, respectively. The frequency of DIND in the EC group was significantly less than that in the SC group (11.8% vs. 17.7%; p = 0.016). In the results of multivariate analysis, internal carotid artery (ICA) aneurysm and hemorrhagic complications were the risk factors for DIND. Cilostazol administration and EC were significant factors for vasospasm prevention after aneurysmal SAH (odds ratio of ICA aneurysm: 1.59, hemorrhagic complications: 1.76, SC: 1.51, and cilostazol administration: 0.51, respectively). Cilostazol administration was also a significant factor in patients who were treated with EC. ICA aneurysm, treatment strategy, hemorrhagic complications, and cilostazol administration were associated with DIND. Oral administration of cilostazol and avoiding hemorrhagic complications were effective in DIND prevention. If both treatments are available for ruptured aneurysms, clinicians should choose EC on the basis of its ability to prevent DIND.

Rationale: As the SARS-COV-2 virus spread across the world in the early months of 2020, people sought to make sense of the complex and rapidly evolving situation by adopting mindsets about what the pandemic was and what it meant for their lives., Objective: We aimed to measure the mindsets of American adults over the first six months of the COVID-19 pandemic to understand their relative stability over time and their relationship with emotions, behaviors, experiences, and wellbeing., Methods: American adults (N = 5,365) were recruited in early March of 2020 to participate in a longitudinal survey with follow-up surveys at 6-weeks and 6-months. Three mindsets that people formed about the COVID-19 pandemic were measured: 'the pandemic is a catastrophe', 'the pandemic is manageable' and 'the pandemic can be an opportunity'., Results: In line with our pre-registered hypotheses, these mindsets were associated with a unique and largely self-fulfilling pattern of emotions (positive, negative), behaviors (healthy, unhealthy, and compliance with CDC guidelines), experiences (growth/connection, isolation/meaninglessness) and wellbeing (physical health, mental health, quality of life). Moreover, mindsets formed in the first week of the pandemic were associated with quality of life 6 months later, an effect that was mediated by emotions and health behaviors., Conclusion: The mindsets that people adopted about the COVID-19 pandemic - that it is 'a catastrophe', 'manageable', or 'an opportunity' may explain some of the heterogeneity in the lived experiences of Americans through their self-fulfilling impact on peoples' emotions, health behaviors, and wellbeing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Copolymer (Onyx) embolization is an effective treatment for dural arteriovenous fistula (dAVF), however, some dAVFs have multiple, high-flow feeding vessels, resulting in insufficient embolization. For the treatment of such patients, we have developed a novel flow-control technique, the 'damp-and-push technique'. The purpose of this study was to evaluate the technical efficiency and safety of this technique., Methods: Seven patients who had been diagnosed with intracranial dAVF were treated by transarterial Onyx embolization using the damp-and-push technique between 2016 and 2019. This technique was designed to reduce blood flow to the shunt site using a balloon catheter in the major feeding vessel other than the one injected with Onyx, leading to better Onyx penetration and enabling more controlled embolization of complex dAVFs. Retrospectively collected data were reviewed to assess the occlusion rates and clinical outcomes., Results: The dAVF was at a transverse sinus-sigmoid sinus junction in four patients, in the superior sagittal sinus in two, and in the tentorium in one. Five cases were Cognard type Ⅱb and two cases were Cognard type Ⅳ. All the patients were treated by transarterial Onyx injection via the main feeding vessel, combined with flow reduction in the other main feeding vessel using a balloon catheter. Complete occlusion was achieved in six patients and elimination of cerebral venous reflux was achieved in all the patients. There were no immediate or delayed post-interventional complications., Conclusions: Transarterial Onyx embolization of dAVF using the damp-and-push technique is safe and yields a high complete occlusion rate., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Backgrounds and Aims: Structural dynamics of basement membrane components are still to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of HCC expressing laminin γ2 monomer (LG2m), a basement membrane component not detected in normal tissues, for HCC diagnosis. We further determined whether elevated serum LG2m is a risk factor for HCC development in patients with chronic hepatitis C (CHC)., Approach and Results: In HCC cell lines, LG2m was expressed in alpha-fetoprotein (AFP)-negative, CD90-positive cells characterized by highly metastatic natures. Using 14 cell lines and 258 HCC microarray data, we identified that LG2m gene signature was associated with Hoshida's S1/Boyault's G3 molecular subclasses with poor prognosis, which could not be recognized by AFP. Serum LG2m was assessed in 24 healthy donors, 133 chronic liver disease patients, and 142 HCC patients, and sensitivity and specificity of LG2m testing for HCC diagnosis were 62.9% and 70.5%, respectively (cutoff, 30 pg/mL). We evaluated the consequence of LG2m elevation in two independent HCC cohorts (n = 47 and n = 81), and LG2m-high HCC showed poor prognosis with later development of distant organ metastasis (cutoff, 60 pg/mL). LG2m was slightly elevated in a subset of CHC patients, and Kaplan-Meier analysis indicated a high incidence of HCC (n = 70). For validation, we enrolled 399 CHC patients with sustained virological response (SVR) as a multicenter, prospective study, and serum LG2m elevation correlated with a high incidence of HCC in the CHC patients with SVR (P < 0.0001)., Conclusions: LG2m is a predictive biomarker for the development of metastatic HCC. Elevated serum LG2m is an HCC risk in CHC patients who have achieved SVR., (© 2021 by the American Association for the Study of Liver Diseases.)

Gene-protein assay (GPA), a combination of immunohistochemistry and dual in situ hybridization, allows simultaneous visualization of HER2 protein and gene on a single slide. We aimed to clarify the clinical significance of HER2 intratumoral heterogeneity (ITH) using GPA. We investigated the relationships between various HER2 ITH indicators and clinical course in 102 patients with HER2-positive breast cancer, treated with neoadjuvant trastuzumab and chemotherapy. Five representative microscopic images were captured from each GPA slide of pre-therapeutic biopsy materials. All evaluable cancer cells in the images were individually assessed for HER2 gene copy number and protein expression. Mean and coefficient of variation (CV) of both gene copy number and protein category were calculated, and each was divided into negative, equivocal, and positive. Based on their combined status, cancer cells were classified into nine types. Pathological complete response (pCR) to neoadjuvant treatments showed positive relationships to mean gene copy number (P < 0.001), mean protein category (P < 0.001), and proportion of gene- and protein-positive tumor cells (P < 0.001) and showed negative relationships to the CV of protein category (P < 0.001) and the proportion of gene-amplified but protein-negative tumor cells (P = 0.002). Two diagnostic models, created by combining clinicopathological factors and ITH indicators, showed excellent potential diagnostic ability for pCR (mean gene copy number and protein category CV; AUC = 0.837, proportion of gene- and protein-positive tumor cells; AUC = 0.831). HER2 ITH quantified by GPA is a potential predictive indicator for efficacy of HER2-targeted treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The development of robust and thin CO 2 separation membranes that allow fast and selective permeation of CO 2 will be crucial for rebalancing the global carbon cycle. Hydrogels are attractive membrane materials because of their tunable chemical properties and exceptionally high diffusion coefficients for solutes. However, their fragility prevents the fabrication of thin defect-free membranes suitable for gas separation. Here, we report the assembly of defect-free hydrogel nanomembranes for CO 2 separation. Such membranes can be prepared by coating an aqueous suspension of colloidal hydrogel microparticles (microgels) onto a flat, rough, or micropatterned porous support as long as the pores are hydrophilic and the pore size is smaller than the diameter of the microgels. The deformability of the microgel particles enables the autonomous assembly of defect-free 30-50 nm-thick membrane layers from deformed ∼15 nm-thick discoidal particles. Microscopic analysis established that the penetration of water into the pores driven by capillary force assists the assembly of a defect-free dense hydrogel layer on the pores. Although the dried films did not show significant CO 2 permeance even in the presence of amine groups, the permeance dramatically increased when the membranes are adequately hydrated to form a hydrogel. This result indicated the importance of free water in the membranes to achieve fast diffusion of bicarbonate ions. The hydrogel nanomembranes consisting of amine-containing microgel particles show selective CO 2 permeation (850 GPU, α CO2/N2 = 25) against post-combustion gases. Acid-containing microgel membranes doped with amines show highly selective CO 2 permeation against post-combustion gases (1010 GPU, α CO2/N2 = 216) and direct air capture (1270 GPU, α CO2/N2 = 2380). The membrane formation mechanism reported in this paper will provide insights into the self-assembly of soft matters. Furthermore, the versatile strategy of fabricating hydrogel nanomembranes by the autonomous assembly of deformable microgels will enable the large-scale manufacturing of high-performance separation membranes, allowing low-cost carbon capture from post-combustion gases and atmospheric air.

Objective: The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen's criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists., Methods: We held slide conferences, where photomicrographs of haematoxylin-eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics., Results: In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753)., Conclusion: Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up., Materials and Methods: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle,  <160°), inner convexity type (included angle,  >200°), and lateral wall type (160° ≤ included angle  ≤200°). This classification reflects the metal coverage rate and flow dynamics., Results: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P  = .001), aneurysms with the branching artery from the dome (OR, 10.56; P  = .002), fusiform aneurysms (OR, 10.2; P  = .009), and outer convexity-type saccular aneurysms (versus inner convexity type: OR, 30.3; P  < .001; versus lateral wall type: OR, 9.71; P  = .001) were independently associated with a higher rate of incomplete occlusion at the last follow-up. No permanent neurologic deficits or rupture were observed in the follow-up period., Conclusions: The aneurysm neck located on the outer convexity is a new, incomplete occlusion predictor, joining older age, fusiform aneurysms, and aneurysms with the branching artery from the dome. No permanent neurologic deficits or rupture was observed in the follow-up, even with incomplete occlusion., (© 2021 by American Journal of Neuroradiology.)

Objective: The efficacy and safety of acute percutaneous transluminal angioplasty or stenting (PTA/PTAS) for vertebrobasilar artery occlusion with atherothrombotic brain infarction (ATBI) have not been confirmed despite the resistance to medical therapy alone. There are few reports about this disease and its treatment. Therefore, the treatment outcomes at our hospital were summarized to evaluate the efficacy and safety., Methods: This was a retrospective study of acute PTA/PTAS for vertebrobasilar artery occlusion due to atherosclerotic change in 19 consecutive patients with a modified Rankin Scale (mRS) score of 0-2 before stroke between March 2010 and December 2018. The factors related to prognosis were investigated. Outcomes were assessed at 90 days of follow-up., Results: Of 19 patients with acute vertebrobasilar artery occlusion treated by PTA/PTAS, 8 had good outcomes (mRS 0-2) and 11 had poor outcomes (mRS 3-6). There were no differences in the clinical or patient background except for the National Institutes of Health Stroke Scale (NIHSS) score between groups. The good outcome group had a lower NIHSS score than the poor outcome group (median: 9.5 vs 35, p <0.001). The Thrombolysis in Cerebral Ischemia (TICI) 2b-3 group had a slightly more favorable outcome than the TICI0-2a group (p = 0.10). There were no differences in outcome between PTA and PTAS groups (p = 0.65)., Conclusion: Reperfusion of the posterior circulation by PTA/PTAS may be necessary for a good outcome. Although acute stenting must be performed under careful observation, a stent can be placed when recurrence in the early phase is estimated with high probability., Competing Interests: Hirotoshi Imamura received rewards as lecture fees from Stryker Japan and Medtronic Japan. Nobuyuki Sakai received research funds from Terumo Corporation, and rewards as lecture fees from Biomedical Solutions, Johnson & Johnson, Medtronic Japan, Penumbra, Stryker Japan, and Terumo Corporation. The remaining authors declare no conflicts of interest regarding the publication of this article., (©2021 The Japanese Society for Neuroendovascular Therapy.)

Purpose: Strain elastography for imaging lesion stiffness is being used as a diagnostic aid in the malignant/benign discrimination of breast diseases. While acquiring elastography in addition to B-mode images has been reported to help avoid performing unnecessary biopsies, intraductal lesions are difficult to discriminate whether they are malignant or benign using elastography. An objective evaluation of strain in lesions was performed in this study by measuring the elasticity index (E-index) and elasticity ratio (E-ratio) of lesions as semi-quantitative numerical indicators of the color distribution of strain. We examined whether ductal carcinoma in situ (DCIS) and intraductal papilloma could be distinguished using these semi-quantitative numerical indicators., Methods: In this study, 170 ultrasonographically detected mass lesions in 162 cases (106 malignant lesions and 64 benign lesions)-in which tissue biopsy by core needle biopsy and vacuum-assisted biopsy, or surgically performed histopathological diagnosis, was performed-were selected as subjects from among 1978 consecutive cases (from January 2014 to December 2016) in which strain elastography images were acquired, in addition to standard B-mode breast ultrasonography, by measuring the E-index and E-ratio., Results: The cut-off values for E-index and E-ratio in the malignant/benign discrimination of breast lesions were determined to be optimal values at 3.5 and 4.2, respectively, based on receiver operating characteristic (ROC) curve analysis. E-index sensitivity, specificity, accuracy, and AUC value (area under the curve) were 85%, 86%, 85%, and 0.860, respectively, while those for E-ratio were 78%, 74%, 74%, and 0.780, respectively. E-index yielded superior results in all aspects of sensitivity, specificity, accuracy, and AUC values, compared to those of E-ratio. The mean E-index values for malignant tumors and benign tumors were 4.46 and 2.63, respectively, indicating a significant difference (P < 0.001). E-index values of 24 DCIS lesions and 25 intraductal papillomas were 3.88 and 3.35, respectively, which showed a considerably close value, while the false-negative rate for DCIS was 29.2%, and the false-positive rate for intraductal papilloma was as high as 32.0%., Conclusion: E-index in strain elastography yielded better results than E-ratio in the malignant/benign discrimination of breast diseases. On the other hand, E-index has a high false-negative rate and false-positive rate for intraductal lesions, a factor which should be taken into account when making ultrasound diagnoses.

Background: Although Ki67 has important clinical relevance in breast cancer, its assessment results vary according to assay due to differences in both analytical and interpretation processes. We aimed to validate the performance of anti-Ki67 antibody clone 30-9 by comparison with clone MIB-1 and to investigate utility of the image analysis system in Ki67 assessment using clinical breast cancer samples., Methods: A series of sequential tissue sections was prepared from formalin-fixed paraffin-embedded blocks of surgically resected breast cancer specimens from 50 patients. The tissue sections were stained immunohistochemically with anti-Ki67 antibodies, 30-9 and MIB-1, as well as with hematoxylin and eosin for morphological analysis. We scanned all the stained slides with Ventana iScan HT and selected the Ki67 counting areas based on morphological findings. Three pathologists independently studied images of the counting areas to determine Ki67-positive rates. In addition, the images of 30-9-stained slides were analyzed using the image analysis system, VENTANA Virtuoso., Results: Ki67-positive rates by 30-9 showed a strong correlation with those by MIB-1 for all pathologists (pathologist #1: r = 0.985, pathologist #2: r = 0.987, pathologist #3: r = 0.982). Between 30-9 and MIB-1, there was no significant difference of CV%, showing variabilities of Ki67-positive rates among pathologists. Ki67-positive rates showed a strong correlation between the image analytical values and the pathologist-counted median values (r = 0.952)., Conclusions: The performance of 30-9 is equivalent to that of MIB-1 in Ki67 assessment of breast cancer. The image analysis system can substitute for or support visual counting by a pathologist.

Background: Internal mammary and/or supraclavicular (IM-SC) lymph node (LN) recurrence without distant metastasis (DM) in patients with breast cancer is rare, and there have been few reports on its clinical outcomes., Methods: We enrolled 4237 patients with clinical stage I-IIIC breast cancer treated between January 2007 and December 2012. Clinicopathological features of patients with IM-SC LN recurrence and patients with DM were retrospectively reviewed., Results: With a median follow-up time 78 (range, 13-125) months after the primary operation, 14 (0.3%) had IM-SC LN recurrence without DM and 274 (6.5%) had DM at the first recurrence among 4237 patients. No statistical differences were found in the baseline characteristics of the primary tumor between the two groups. The 5-year overall survival (OS) rate after recurrence in patients with IM-SC LN recurrence was 51% compared with 27% in patients with DM (P = 0.040). In patients with IM-SC LN recurrence, clinically positive axillary LN at diagnosis and pathologically positive axillary LN at primary surgery were poor prognostic factors for distant disease-free survival (DDFS) (P = 0.004 and 0.007, respectively). Clinical and pathological axillary nodal status at primary surgery was associated with OS (P = 0.011 and 0.001, respectively)., Conclusions: Patients with IM-SC LN recurrence without DM who had no clinical and pathological axillary LNs involved at primary surgery had a favorable prognosis. A larger validation study is required.

Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC., Methods: We retrospectively reviewed the data of patients with cytologically proven axillary node-positive disease who received NAC and those with axillary pN- without NAC for control between January 2007 and December 2012. We compared outcomes according to response in the axilla to NAC and between patients with axillary pCR and matched pairs with axillary pN- without NAC using propensity scores., Results: We included 596 patients with node-positive breast cancer who received NAC. The median follow-up period was 64 months. Patients with axillary pCR showed significantly better distant disease-free survival (DDFS) and overall survival (OS) than patients with residual axillary disease (both p < 0.01). There was no significant difference in DDFS and OS between patients with axillary pCR and matched pairs with axillary pN- without NAC., Conclusion: Axillary pCR was associated with improved prognosis. Patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes. This information will be useful when considering the intensity of follow-up and adjuvant therapy.

This retrospective study investigated factors influencing the portal vein thrombosis (PVT) volume and recurrence in 52 cirrhosis patients with PVT from November 2008 to September 2018. All patients were treated with danaparoid sodium with or without additional antithrombin III. Blood platelet counts significantly correlated with the PVT volume (r 2 = 0.17; P < 0.01). Computed tomography confirmed recurrence as PVT aggravation was reported in 43 patients, with ≥50% PVT volume reduction following anticoagulation therapy. In 43 patients, recurrence significantly correlated with the pretreatment PVT volume ( P = 0.019). Factors influencing recurrence included a Child-Pugh score >8 ( P = 0.049) and fibrosis index ≤7.0 based on four factors (FIB-4) ( P = 0.048). Moreover, the relationship between recurrence and correlating factors showed that 15 patients who received warfarin experienced recurrence more often when Child-Pugh scores were >8 ( P = 0.023), regardless of maintenance treatment. For patients who did not receive warfarin, a PVT volume ≥3.0 mL significantly influenced recurrence ( P = 0.039). Therefore, the platelet count influences the PVT volume. The pretreatment PVT volume correlated with recurrence after anticoagulation therapy. According to the Kaplan-Meier curve, risk factors for PVT recurrence after anticoagulation therapy included Child-Pugh scores >8 and FIB-4 ≤7.0. Therefore, the FIB-4 is a unique factor that shows trends opposing other liver function markers.