榊原 淳太

BACKGROUND: AccuVein® can help visualize superficial veins and is generally used as an auxiliary device to identify patterns of veins that are difficult to locate for collecting blood and securing venous lines. Even when venous patterns are obscure via visual inspection and/or palpation, the clear projection/delineation of superficial veins using this apparatus facilitates safe venous puncture and helps secure venous lines. Therefore, this apparatus is widely used in clinical settings. AccuVein® can easily visualize not only superficial veins in the limbs but also the ones located throughout the body surface. CASE PRESENTATION: We report three cases of 68-year-old, 41-year-old, and 56-year-old Japanese women in whom superficial veins in the breasts were visualized using AccuVein®, and mastectomy and partial mastectomy were performed. All patients were of Japanese ethnicity. AccuVein® can enable the examiner to observe superficial veins in the breasts, irrespective of their skills. The examiner can, thus, secure detailed visualization of subcutaneous veins in the breasts. Furthermore, AccuVein® ensures reproducibility and subjectivity regardless of the examiners' experience. During a mastectomy, the perforating branches of the internal thoracic vein originating from the greater pectoral muscle are identified, ligated, and separated. The preoperative use of AccuVein® makes it possible to instantaneously identify their position. Visualizing the perforating branches to their root in patients with thin subcutaneous breast fat and their roots' proximity in patients with thick subcutaneous breast fat is possible. While the position and/or range of a breast cancer lesion may sometimes be unclear in ultrasonography, marking subcutaneous mammary veins around the lesion as the benchmark helps identify the lesion position. In this study, we inspected the patterns of subcutaneous mammary veins using AccuVein®. This manuscript reports the clinical application of this apparatus in breast cancer surgeries. CONCLUSION: Understanding the vascular construction of subcutaneous mammary veins using the vein visualization apparatus AccuVein® may serve as an auxiliary technique for safely and securely identifying breast cancer lesions.

Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI's effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI's impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.

INTRODUCTION: Tall cell carcinoma with reversed polarity (TCCRP) is a rare histologic subtype of breast cancer that was newly categorized in 2020. TCCRP is a relatively novel tumor, and there are no detailed reports about its cellular morphology. We were able to obtain imprint cytological specimens from fresh TCCRP tissue, and we provide our detailed observations. CASE PRESENTATION: The patient was a 73-year-old Japanese female with a 15-mm mass in her right breast. After invasive breast carcinoma was diagnosed based on a core needle biopsy, a lumpectomy was performed. The pathological examination revealed TCCRP, and Sanger sequencing detected IDH2 p.R172M hotspot mutation, which is characteristic of TCCRP. Soon after the surgery, the lumpectomy specimen was sliced before fixation for use in a clinical trial, and imprint cytological materials were obtained from the tumor's cut surface. Cytologically the tumor showed papillary-like cell clusters and isolated cells with moderate cellularity. Neoplastic cell aggregates and clusters with thick vascular cores as the axis or with delicate fibrovascular stroma were observed. Most of the neoplastic cells were cuboidal-to-columnar in shape, with mildly to moderately irregularly shaped blunt nuclei. Some intranuclear cytoplasmic inclusions and nuclear grooves were present, resembling the nuclear findings of papillary thyroid carcinoma. The most characteristic finding was the columnar cell clusters with apically located nuclei, giving the impression of reversed polarity. CONCLUSION: We identified cytological findings in TCCRP, a newly classified rare mammary tumor. Most of the characteristic histological findings were also observed in cytological specimens. Although this study was of imprint cytology, we note that cytology is useful in the preoperative diagnosis of TCCRP.

BACKGROUND: Although targeted treatments against human epidermal growth factor receptor 2 (HER2) have improved survival in patients with metastatic HER2-positive breast cancer, long and repeated treatment is time-consuming and costly for patients. To reduce these burdens, we developed ex vivo gene-transduced adipocytes that secrete anti-HER2 antibodies and evaluated their anti-tumor effects. METHODS: Ceiling culture-derived proliferative adipocytes (ccdPA) secreting anti-HER2 antibody against domain IV receptors: TRA-ccdPA, and domain II receptors: PER-ccdPA, were constructed using a plasmid lentivirus. Delivery of secreted antibody and its specific binding to HER2 breast cancer were evaluated in vitro and in vivo. To optimize antibody production from ccdPA, different conditions of ccdPA implantation were examined. Anti-tumor efficacy was evaluated in HER2-positive-cancer-inoculated nude mice. RESULTS: Anti-HER2 antibody against domain II was identified in supernatants from PER-ccdPAs. The optimal method to achieve the highest concentration of antibody in mouse sera was injecting differentiated ccdPA cells into the mammary fat pad. Antibody in supernatants from PER-ccdPAs bound to the surface of HER2-positive breast cancer cells similar to pertuzumab. Antibodies in mouse sera were delivered to HER2-positive breast cancer tumors and tumor necrosis was observed microscopically. One-time administration of combined TRA-ccdPAs and PER-ccdPAs produced antibody continuously in mouse sera, and anti-tumor effects were maintained for the duration of this study in xenograft models. Furthermore, combination therapy significantly suppressed tumor growth compared with a single administration. CONCLUSION: Ex vivo gene-transduced adipocytes might be useful for cell-based gene therapy. This system may be a platform for various antibody therapies.