[Treatment Strategy for HER2 Positive and HER2 Low Breast Cancer].

Human epidermal growth factor receptor 2(HER2)positive breast cancer has been regarded as a poor prognosis breast cancer, but since the development of trastuzumab and various anti-HER2 drugs, the prognosis has significantly improved. Also, combining anti-HER2 drugs with chemotherapy as preoperative treatment, shows high ratings of pathological complete response(pCR). In terms of breast cancer, pCR is a prognosis predictive factor. As a result, in perioperative treatment for HER2 positive breast cancer, residual disease-guided approach which means to select postoperative treatment according to the response to preoperative chemotherapy has become the main stream. Furthermore, trastuzumab deruxtecan, which had been covered by insurance only for HER2 positive metastatic or recurrent breast cancer, was newly reimbursed for breast cancer with low HER2 expression at the end of March 2023, and the future movement is attracting attention.

Serum 25-hydroxycholesterol levels are increased in patients with coronavirus disease 2019.

BACKGROUND: 25-hydroxycholesterol (25HC), produced by cholesterol 25-hydroxylase (CH25H) in macrophages, has been reported to inhibit the replication of viral pathogens such as severe acute respiratory syndrome coronavirus-2. Also, CH25H expression in macrophages is robustly induced by interferons (IFNs). OBJECTIVE: To better understand the serum level increase of 25HC in coronavirus disease 2019 (COVID-19) and how it relates to the clinical picture. METHODS: We measured the serum levels of 25HC and five other oxysterols in 17 hospitalized COVID-19 patients. RESULTS: On admission, 25HC and 27-hydroxycholesterol (27HC) serum levels were elevated; however, 7-ketocholesterol (7KC) levels were lower in patients with COVID-19 than in the healthy controls. There was no significant correlation between 25HC serum levels and disease severity markers, such as interferon-gamma (IFN-γ) and interleukin 6. Dexamethasone effectively suppressed cholesterol 25-hydroxylase (CH25H) mRNA expression in RAW 264.7 cells, a murine leukemia macrophage cell line, with or without lipopolysaccharide or IFNs; therefore, it might mitigate the increasing effects of COVID-19 on the serum levels of 25HC. CONCLUSIONS: Our results highlighted that 25HC could be used as a unique biomarker in severe COVID-19 and a potential therapeutic candidate for detecting the severity of COVID-19 and other infectious diseases.

Inhibition of xanthine oxidase activity by an oxathiolanone derivative of quercetin.

An oxathiolanone derivative of rutin could be produced in the stomach after the ingestion of rutin containing foods, and the oxathiolanone derivative could be hydrolysed to an oxathiolanone derivative of quercetin (quercetin-oxathiolanone) in the intestine. Quercetin-oxathiolanone as well as quercetin inhibited xanthine oxidase. Approximately 0.05µM quercetin-oxathiolanone inhibited the activity by 50%, whereas 50% inhibition by quercetin was observed at approximately 0.4µM. The results suggested that quercetin-oxathiolanone can be used as an effective inhibitor of xanthine oxidase and that the ingestion of rutin-rich foods may be useful to prevent the increase in the blood concentration of uric acid.

Multiple self-healing squamous epithelioma in different ethnic groups: more than a founder mutation disorder?

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith Disease, is a rare cancer-associated genodermatosis with an autosomal dominant inheritance. Affected patients suffer from recurrent skin lesions, which clinically and histologically resemble keratoacanthomas or well-differentiated squamous cell carcinomas, but which, if left, undergo spontaneous regression, leaving pronounced scarring. The majority of MSSE cases previously described were of Scottish ancestry and all shared the same at-risk haplotype, suggesting that this disorder was caused by a founder mutation. The candidate locus for MSSE lies in a region of <4 cM in chromosome 9q22, between the markers D9S197 and D9S1809. We recently investigated MSSE families of non-Scottish origin. For every patient of these families, we obtained a detailed clinical history, with particular attention to the age of onset, distribution, and clinical course of their skin lesions. Once confirmed that they were really affected by MSSE, we performed haplotype analysis on them and their families. The haplotypes for polymorphic markers segregating with MSSE in non-Scottish and Scottish families differ, suggesting that MSSE is not caused by a founder mutation and might be more common than originally thought.

Hemi-orbicularis oculi switch flap for upper eyelid defects.

BACKGROUND: The technique chosen to reconstruct anterior lamellar defects of the upper eyelid requires careful consideration. We modified pre-existing techniques used to reconstruct anterior lamellar defects after tumour resection and have called this procedure a hemi-orbicularis oculi switch flap. METHODS: This musculocutaneous flap is elevated with underlying orbicularis and its base abuts the anterior lamellar defect. The flap, which is half the height of the defect, is elevated and inset to cover the defect. Then, taking into consideration the extensibility of upper eyelid skin, the remainder of the defect and the donor site are closed directly. RESULTS: Five patients with basal cell carcinoma, haemangioma, and xanthoma of the upper eyelid were treated by this method. All flaps survived and complications were minimal. Aesthetically and functionally good results were obtained by this method. CONCLUSIONS: We have developed a surgical method for the reconstruction of anterior lamellar defects of the upper eyelid. The proposed method is technically simple and safe and provides consistent results for a potentially wide variety of upper eyelid tumours.

Recovery course of full-thickness skin defects with exposed bone: an evaluation by a quantitative examination of new blood vessels.

BACKGROUND: Full-thickness skin defects with exposed bone are often hard to heal. The lack or delayed re-vascularization is considered one of the major causes, and the periosteum is also suggested to have an important role in tissue regeneration. MATERIALS AND METHODS: Full-thickness skin defect wounds with exposed bone were made in the parietal region of Wister rats. The periosteum of the exposed parietal bone was removed in the periosteum-lacking group, but maintained in the control group (periosteum-intact group). The wound was covered by an artificial dermis made of collagen. The wound healing process was histologically compared. Double immunostaining of alpha-smooth muscle actin (SMA) and von Willebrand factor (vWF) was used for re-vascularization examination, and the blood vessel density in the artificial dermis was quantified. RESULTS: The density of the blood vessels in the uninjured parietal tissue was approximately 80 vessels/mm(2). To reach this density, 7 and 21 days were required for the control (periosteum-intact) and the periosteum-lacking groups, respectively. This coincided with complete revascularization, fibroblast migration and the reentry of blood vessels to the upper layer of the wound were observed. CONCLUSION: The described results support the importance of the periosteum in the full-thickness skin defect healing process.

Bilateral modified V-Y advancement flaps for closing meningomyelocele defects.

Various reports describe surgical techniques for closing a meningomyelocele defect. We have used a combination flap consisting of a vertical bipedicled flap and V-Y advancement flap and used this technique in the successful repair of 11 meningomyelocele defects. The vertical bipedicled flap enhances the blood supply to the V-Y advancement flap with no sacrifice of muscle tissue. This flap can easily be moved to the midline, and the donor area can be primarily sutured with no complications. Our method has several advantages compared with previously reported methods: 1) no skin grafts are needed; 2) no muscle tissue is killed; 3) it is simple and easy, leading to less blood loss and minimal operative time; and 4) it is safe and produces reliable results while eliminating wound dehiscence and skin necrosis.