Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn.

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.

IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death.

Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway.

An automatic immuno-microfluidic system integrating electrospun polystyrene microfibrous reactors for rapid detection of salivary cortisol.

Conventional competitive enzyme-linked immunosorbent assay (ELISA) to measure the cortisol level in body fluid consumes a large amount of time, owing to complicated operations involved and requirement for precise control of reagent addition. We developed an automatic microfluidic system to detect salivary cortisol rapidly, and an electrospun polystyrene (PS) microfiber-based reactor providing considerable binding sites for antibody immobilization, thus resolving the time limitations of competitive ELISA. Cortisol sample, horseradish peroxidase (HRP)-conjugated cortisol, and 3,3',5,5'-tetramethylbenzidine (TMB) substrate were delivered to the PS reactor from containers in sequence by pumps automatically. The color variation due to oxidized TMB complex reflects the cortisol concentration level measured using an RGB phototransistor. In addition, the entire procedure from sample introduction to obtaining the photocurrent took only 15 min. This system can be implemented to quantify cortisol from 0.37 ng/mL to 30 ng/mL, and the limit of detection was estimated at 0.37 ng/mL.

Cardiac Autoantibodies Against Cardiac Troponin I in Post-Myocardial Infarction Heart Failure: Evaluation in a Novel Murine Model and Applications in Therapeutics.

BACKGROUND: Cardiac autoantibodies (cAAbs) are involved in the progression of adverse cardiac remodeling in heart failure (HF). However, our understanding of cAAbs in HF is limited owing to the absence of relevant animal models. Herein, we aimed to establish and characterize a murine model of cAAb-positive HF after myocardial infarction (MI), thereby facilitating the development of therapeutics targeting cAAbs in post-MI HF. METHODS: MI was induced in BALB/c mice. Plasma cAAbs were evaluated using modified Western blot-based methods. Prognosis, cardiac function, inflammation, and fibrosis were compared between cAAb-positive and cAAb-negative MI mice. Rapamycin was used to inhibit cAAb production. RESULTS: Common cAAbs in BALB/c MI mice targeted cTnI (cardiac troponin I). Herein, 71% (24/34) and 44% (12/27) of the male and female MI mice, respectively, were positive for cAAbs against cTnI (cTnIAAb). Germinal centers were formed in the spleens and mediastinal lymph nodes of cTnIAAb-positive MI mice. cTnIAAb-positive MI mice showed progressive cardiac remodeling with a worse prognosis (P=0.014, by log-rank test), which was accompanied by cardiac inflammation, compared with that in cTnIAAb-negative MI mice. Rapamycin treatment during the first 7 days after MI suppressed cTnIAAb production (cTnIAAb positivity, 59% [29/49] and 7% [2/28] in MI mice treated with vehicle and rapamycin, respectively; P<0.001, by Pearson χ2 test), consequently improving the survival and ameliorating cardiac inflammation, cardiac remodeling, and HF in MI mice. CONCLUSIONS: The present post-MI HF model may accelerate our understanding of cTnIAAb and support the development of therapeutics against cTnIAAbs in post-MI HF.

Development of microfluidic devices for on-site water quality testing using glass molding process.

The demand for multi-point water quality monitoring is increasing to solve the global problem of safe drinking water supply and environmental water contamination by industries. Therefore, compact devices are needed for on-site water quality analysis. On-site devices require low cost and high durability because they are placed outdoors, exposing them to strong ultraviolet rays and a wide range of temperatures. Our previous study reported on a compact and low-cost water quality meter that uses microfluidic devices with resin to monitor chemicals. In this study, we extended the fabrication range of the glass molding method to fabricate a glass microfluidic device with a 300 µm deep channel on a 50 mm in diameter substrate for constructing a low-cost and high-durability device. Finally, we developed a low-cost, highly robust glass device with a diamond-like carbon-coated channel surface to measure residual chlorine. The experimental results indicated that this device can endure outdoor conditions and be attached to small internet of things devices for analyzing chemical substances, such as residual chlorine.

ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts.

BACKGROUND: Mitochondrial DNA (mtDNA)-induced myocardial inflammation is intimately involved in cardiac remodeling. ZBP1 (Z-DNA binding protein 1) is a pattern recognition receptor positively regulating inflammation in response to mtDNA in inflammatory cells, fibroblasts, and endothelial cells. However, the role of ZBP1 in myocardial inflammation and cardiac remodeling remains unclear. The aim of this study was to elucidate the role of ZBP1 in mtDNA-induced inflammation in cardiomyocytes and failing hearts. METHODS: mtDNA was administrated into isolated cardiomyocytes. Myocardial infarctionwas conducted in wild type and ZBP1 knockout mice. RESULTS: We here found that, unlike in macrophages, ZBP1 knockdown unexpectedly exacerbated mtDNA-induced inflammation such as increases in IL (interleukin)-1ß and IL-6, accompanied by increases in RIPK3 (receptor interacting protein kinase 3), phosphorylated NF-κB (nuclear factor-κB), and NLRP3 (nucleotide-binding domain and leucine-rich-repeat family pyrin domain containing 3) in cardiomyocytes. RIPK3 knockdown canceled further increases in phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in cardiomyocytes in response to mtDNA. Furthermore, NF-κB knockdown suppressed such increases in NLRP3, IL-1ß, and IL-6 by ZBP1 knockdown in response to mtDNA. CpG-oligodeoxynucleotide, a Toll-like receptor 9 stimulator, increased RIPK3, IL-1ß, and IL-6 and ZBP1 knockdown exacerbated them. Dloop, a component of mtDNA, but not Tert and B2m, components of nuclear DNA, was increased in cytosolic fraction from noninfarcted region of mouse hearts after myocardial infarction compared with control hearts. Consistent with this change, ZBP1, RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6 were increased in failing hearts. ZBP1 knockout mice exacerbated left ventricular dilatation and dysfunction after myocardial infarction, accompanied by further increases in RIPK3, phosphorylated NF-κB, NLRP3, IL-1ß, and IL-6. In histological analysis, ZBP1 knockout increased interstitial fibrosis and myocardial apoptosis in failing hearts. CONCLUSIONS: Our study reveals unexpected protective roles of ZBP1 against cardiac remodeling as an endogenous suppressor of mtDNA-induced myocardial inflammation.

Trends in Primary Tooth Emergence Pattern and Associated Factors in Japanese Infants.

OBJECTIVE: The purposes of this study were to analyse trends in primary tooth emergence patterns and to identify physical factors potentially associated with them. METHODS: The participants were 27,454 infants who underwent routine 18-month-old health examinations in Ebetsu City, Japan, between 1980 and 2012. This study was conducted using data from infants' 18-month-old health examinations over a 33-year period. The mean number of emerged primary teeth was analysed by sex using a general linear model. For logistic regression analysis, the proportion of infants with 16 emerged teeth or more at 18 months old was used as a dependent variable. Examination year; birth order; birth weight; weight, height, and chest girth at 18 months old; number of fused teeth; and mother's age were used as independent variables. RESULTS: The mean number of emerged primary teeth decreased over the 33-year period. Birth weight and weight and height at 18 months old decreased, and the proportion of low-birth-weight (<2500 g) infants increased over the 33-year period. On general linear model analysis, the yearly change in the mean number of emerged primary teeth was -0.0188 for boys and -0.0181 for girls. Birth weight and weight and height at 18 months old were significantly associated with the presence of 16 emerged primary teeth or more, according to the logistic regression analysis. CONCLUSIONS: The results demonstrated that, over the 33-year period examined, the mean number of emerged primary teeth decreased and birth weight and weight and height at 18 months old were associated with the pattern of tooth emergence.

Posterior Epidural Migrated Lumbar Disc Fragment at L2-3 Level Mimicking an Extradural Spinal Tumor: A Case Report.

Introduction: Disc sequestration is well known as a perforation of the fibrous ring and posterior longitudinal ligament, and migration of the fragment to the epidural space. Case Report: A 62-year-old man complained of increased pain and hypoesthesia and muscle weakness of the left lower limb that had started 1 month before. Magnetic resonance imaging revealed a tumor-like mass at the L2-3 level on the posterior side of the dura. The fragment was strongly adhered to the dural sac and was resected piece by piece. Disc herniation recognized at L2-3 compressed the left L3 nerve root and was removed. The histopathological diagnosis was consistent with a degenerated intervertebral disc. All symptoms improved after the surgery. Conclusion: There are few reports about the posterior migrated disc herniation at higher lumbar level. It may be associated with fused segments from L4 to the pelvis due to the previous surgery, which impacted the adjacent segment.

A Mediated Enzymatic Electrochemical Sensor Using Paper-Based Laser-Induced Graphene.

Laser-induced graphene (LIG) has been applied in many different sensing devices, from mechanical sensors to biochemical sensors. In particular, LIG fabricated on paper (PaperLIG) shows great promise for preparing cheap, flexible, and disposable biosensors. Distinct from the fabrication of LIG on polyimide, a two-step process is used for the fabrication of PaperLIG. In this study, firstly, a highly conductive PaperLIG is fabricated. Further characterization of PaperLIG confirmed that it was suitable for developing biosensors. Subsequently, the PaperLIG was used to construct a biosensor by immobilizing glucose oxidase, aminoferrocene, and Nafion on the surface. The developed glucose biosensor could be operated at a low applied potential (-90 mV) for amperometric measurements. The as-prepared biosensor demonstrated a limit of detection of (50-75 µM) and a linear range from 100 µM to 3 mM. The influence of the concentration of the Nafion casting solution on the performance of the developed biosensor was also investigated. Potential interfering species in saliva did not have a noticeable effect on the detection of glucose. Based on the experimental results, the simple-to-prepare PaperLIG-based saliva glucose biosensor shows great promise for application in future diabetes management.

Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis.

Clinical use of doxorubicin (DOX) is limited because of its cardiotoxicity, referred to as DOX-induced cardiomyopathy (DIC). Mitochondria-dependent ferroptosis, which is triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DIC. Here, we showed that DOX accumulated in mitochondria by intercalating into mitochondrial DNA (mtDNA), inducing ferroptosis in an mtDNA content-dependent manner. In addition, DOX disrupted heme synthesis by decreasing the abundance of 5'-aminolevulinate synthase 1 (Alas1), the rate-limiting enzyme in this process, thereby impairing iron utilization, resulting in iron overload and ferroptosis in mitochondria in cultured cardiomyocytes. Alas1 overexpression prevented this outcome. Administration of 5-aminolevulinic acid (5-ALA), the product of Alas1, to cultured cardiomyocytes and mice suppressed iron overload and lipid peroxidation, thereby preventing DOX-induced ferroptosis and DIC. Our findings reveal that the accumulation of DOX and iron in mitochondria cooperatively induces ferroptosis in cardiomyocytes and suggest that 5-ALA can be used as a potential therapeutic agent for DIC.

Development of cellulosic material-based microchannel device capable of fluorescence immunoassay of microsamples.

Microfluidic immunoassay devices are a promising technology that can quickly detect biomarkers with high sensitivity. Recently, many studies implementing this technology on paper substrates have been proposed for improving cost and user-friendliness. However, these studies have identified problems with the large volume of sample required, low sensitivity, and a lack of quantitative accuracy and precision. In this paper, we report a novel structure implemented as a cellulosic material-based microchannel device capable of quantitative immunoassay using small sample volumes. We fabricated microfluidic channels between a transparent cellophane film and water-resistant paper to facilitate loading of small-volume samples and reagents, with a 40-µm-wide immunoreaction matrix constructed in the center of the microchannel using highly precise photolithography. A fluorescence sandwich immunoassay for C-reactive protein (CRP) was successfully implemented that required only a 1-µL sample volume and a 20-min reaction time. We confirmed that the limit of detection of the device was 10-20 ng/mL with a coefficient of variation under 5.6%, which is a performance level comparable to conventional plastic-based human CRP enzyme-linked immunosorbent assay (ELISA) kits. We expect that such devices will lead to the elimination of large amounts of medical waste from the use of ubiquitous diagnostics, a result that is consistent with environmental sustainability goals.

Cell Adhesion and Migration on Thickness Gradient Bilayer Polymer Brush Surfaces: Effects of Properties of Polymeric Materials of the Underlayer.

In the field of tissue engineering and biomaterials, controlling the surface properties and mechanical properties of scaffold materials is crucial and has attracted much attention. Here, two types of bilayer polymer brushes composed of a hydrophilic underlying layer and a cationic surface layer [made of poly(2-aminoethyl methacrylate)] with a thickness gradient were prepared by surface-initiated atom-transfer radical polymerization. To investigate the influence of the stiffness as a mechanical property of the polymer brush on cell behavior, the underlayer was prepared from either 2-methacryloyloxyethyl phosphorylcholine or oligo(ethylene glycol) methyl ether methacrylate, with the bilayers designated as gradient poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(2-aminoethyl methacrylate) [grad-pMbA] and gradient poly(oligo[ethylene glycol] methyl ether methacrylate)-block-poly(2-aminoethyl methacrylate) [grad-pEGbA], respectively. Characterization of these surfaces was performed by spectroscopic ellipsometry, X-ray reflectivity, and determination of the zeta potential, static contact angle, and force curve. These diblock copolymer brushes with a thickness gradient helped to distinguish the effects of the mechanical and surface properties of the brushes on cell behavior. The attachment and motility of L929 fibroblasts and epithelial MCF 10A cells on the fabricated brushes were then assessed. L929 cells had a round shape on the thin surface layer of grad-pMbA and spread well on thicker areas. In contrast, MCF 10A cells spread well in areas of any thickness of either grad-pMbA or grad-pEGbA. Single MCF 10A cells migrated randomly on grad-pMbA, whereas grouped cells started to climb up along the thickness gradient of grad-pMbA. In contrast, both single and grouped MCF 10A cells migrated randomly on grad-pEGbA. These thickness gradient diblock copolymer brushes are simple, reproducible, and reasonable platforms that can facilitate practical applications of biomaterials, for example, in tissue engineering and biomaterials.

GFAT2 mediates cardiac hypertrophy through HBP-O-GlcNAcylation-Akt pathway.

Molecular mechanisms mediating cardiac hypertrophy by glucose metabolism are incompletely understood. Hexosamine biosynthesis pathway (HBP), an accessory pathway of glycolysis, is known to be involved in the attachment of O-linked N-acetylglucosamine motif (O-GlcNAcylation) to proteins, a post-translational modification. We here demonstrate that glutamine-fructose-6-phosphate amidotransferase 2 (GFAT2), a critical HBP enzyme, is a major isoform of GFAT in the heart and is increased in response to several hypertrophic stimuli, including isoproterenol (ISO). Knockdown of GFAT2 suppresses ISO-induced cardiomyocyte hypertrophy, accompanied by suppression of Akt O-GlcNAcylation and activation. Knockdown of GFAT2 does not affect anti-hypertrophic effect by Akt inhibition. Administration of glucosamine, a substrate of HBP, induces protein O-GlcNAcylation, Akt activation, and cardiomyocyte hypertrophy. In mice, 6-diazo-5-oxo-L-norleucine, an inhibitor of GFAT, attenuates ISO-induced protein O-GlcNAcylation, Akt activation, and cardiac hypertrophy. Our results demonstrate that GFAT2 mediates cardiomyocyte hypertrophy by HBP-O-GlcNAcylation-Akt pathway and could be a critical therapeutic target of cardiac hypertrophy.

Evaluation of bacterial adhesion strength on phospholipid copolymer films with antibacterial ability using microfluidic shear devices.

Biomimetic phospholipid copolymer films are known to possess antifouling properties against protein adsorption and biofilm formation. However, the interactions between bacterial cells and material surfaces are not fully understood. This work investigated the bacterial adhesion strength of phospholipid copolymer films using a shear stress-tunable microfluidic device. The copolymer, comprising 2-methacryloyloxyethyl phosphorylcholine (MPC), 3-methacryloxypropyl trimethoxysilane (MPTMSi), and 3-(methacryloyloxy) propyl-tris(trimethylsilyloxy) silane (MPTSSi), formed crosslinked films on glass substrates; the thickness of the coating film was controlled by the polymer concentration during dip-coating. Polymer films with two typical thicknesses, 20 and 40 nm (denoted as C-20 and C-40, respectively), were prepared on the bottom wall of the microfluidic device. After seeding S. aureus in the microfluidic device, several shear stresses were applied to evaluate the adhesion strength of the polymer films. S. aureus was found to have weaker adhesion strength on the C-40 surface than on the C-20 surface; numerous bacterial cells detached from the C-40 surface on application of identical shear stress. To mimic the presence of plasma protein, fibrinogen (Fg) was introduced into the device before performing the bacterial adhesion assay. The results showed that the adsorption of Fg promoted S. aureus adhesion and strong interactions under shear stress. However, the adhesion strength of S. aureus did not affect the Fg adsorption for both the C-20 and C-40 surfaces. Using the shear stress-tunable microfluidic device, we found that the adhesion of S. aureus on the thicker and softer phospholipid copolymer was weak, and the cells easily detached under high shear stress.

A needle-type micro-sampling device for collecting nanoliter sap sample from plants.

In plant research, measuring the physiological parameters of plants is vital for understanding the behavior and response of plants to changes in the external environment. Plant sap analysis provides an approach for elucidating the physiological condition of plants. However, to facilitate accurate sap analysis, a sampling device capable of collecting sap samples from plants is required. In this paper, a minimally invasive, needle-type micro-sampling device capable of collecting nanoliter (~ 91 nL) quantities of sap from plants is described. The developed micro-sampling system showed great reproducibility (3%) in experiments designed to assess sampling performance. As a proof of concept, sap samples were collected continuously from target plants with the micro-sampling system, and the dynamic changes in potassium ions, plant hormones and sugar levels inside plants were analyzed. The results demonstrated the feasibility of the micro-sampling device and its potential for developing a measurement system for plant research in the future.

Fluidic Patch Device to Sample Sweat for Accurate Measurement of Sweat Rate and Chemical Composition: A Proof-of-Concept Study.

Sweat sensors that can continuously sample sweat are critical for determining the time-dependent physiological responses occurring in normal daily life. Here, a new device, termed fluidic patch, for collecting human sweat samples at defined time intervals is developed, and the proof-of-concept is demonstrated. The device comprises micropumps and a disposable microfluidic patch attached to the human skin. The fluidic patch continuously collects aliquots of freshly secreted sweat accumulated in the fluidic pathway at accurately defined time windows (typically 5 min). By measuring the weight of the collected samples, the local sweat rate is calculated. The sweat sample collected can be directly subjected to a wide range of chemical analyses. For the proof-of-concept, we compared the sweat rates during passive heating in human trials using the fluidic patch and the conventional ventilated sweat capsule system. Although the sweat rate obtained using the fluidic patch highly correlated with that of the ventilated sweat capsule (R2 = 0.96, y = 1.4x - 0.05), the fluidic patch overestimated the sweat rate compared with the ventilated capsule system when the sweat rate exceeded 0.5 mg/(cm2·min). The sampled sweat was analyzed for sodium, potassium, chloride, lactate, pyruvate, and cortisol. The device could obtain the time courses of the concentrations of the abovementioned three ions; the concentrations of sodium and chloride increased linearly with the sweat rate during passive heating (R2 = 0.76 and 0.66, respectively). The device can reliably measure the sweat rate and collect sweat samples for chemical analysis. It can be utilized for real-time physiological investigations toward wider applications.

Takotsubo syndrome in a heart transplant recipient with poor cardiac sympathetic reinnervation.

Takotsubo syndrome (TTS), also referred to as stress cardiomyopathy, is characterized by transient left ventricular apical ballooning in the absence of obstructive coronary artery disease. Catecholamine-induced cardiac injury or vasospasm has been implicated in this pathophysiology. We present a case of a 67-year-old man 10 years after heart transplantation diagnosed with TTS. Sympathetic reinnervation could not be detected by iodine-123 meta iodobenzylguanidine uptake, suggesting that TTS can occur in the absence of functional sympathetic nerve systems reconstruction.

Potent Inhibitory Effects of Quercetin on Inflammatory Responses of Collagen-Induced Arthritis in Mice.

BACKGROUND: Production of tumor necrosis factor (TNF)-α by inflammatory cells in lesions is the hallmark of the pathogenesis of rheumatoid arthritis (RA). Regulation of inflammatory responses in knee joints of patients with RA is critical for improving severe symptoms. Flavonoids have inhibitory effects on the acute and chronic inflammatory responses caused by TNF-α. The flavonoid quercetin (QUER) is one of the most prominent dietary antioxidants. OBJECTIVE: The present study investigated the preventive and therapeutic effects of QUER on inflammatory responses in collagen-induced arthritis (CIA) in mice. METHODS: Mice with CIA, a mouse model for RA, were treated with QUER orally three times a week either from the second immunization with collagen (day 21) or day 28 when symptoms of CIA had developed midway. RESULTS: In both cases, inflammation-related clinical scores of knee joints were significantly reduced by treatment with QUER. Histological analyses showed that the representative characteristics of RA, such as damage to interchondral joints, infiltration of inflammatory cells, and pannus formation, were significantly reduced by QUER treatment. Oral administration of QUER significantly decreases lipopolysaccharide (LPS)-induced TNF-α production in a dose-dependent manner. Expression of TNF- α mRNA in knee joints was decreased in QUER-treated mice, compared with those of CIA controls. CONCLUSION: These results suggest that oral administration of QUER might effectively improve symptoms of RA.

Preservation of the nipple-areola complex in skin-sparing mastectomy for early breast cancer.

PURPOSE: Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer while overcoming the cosmetic issues related to surgery. We review our experience of performing SSMs and assess whether preservation of the nipple-areola complex (NAC) could have been an option for some patients who underwent SSM. METHODS: The subjects of this retrospective study were women who underwent SSM that utilized four incision types; namely, the so-called tennis racket incision, a periareolar and midaxillary incision, an areola-sparing and midaxillary incision, and a small transverse elliptical incision. We assessed whether preservation of the NAC would have been an option in SSM, based on histologic examination of three serial cut surfaces of the specimen around the nipple, ruling out the option when evidence of the malignant lesion/s was found in at least one of the following locations: in the nipple, within a 1-cm radius from the base of the nipple, or within 1 cm from the surface of the NAC. RESULTS: We performed 193 SSMs. The cumulative 10-year local disease-free survival rate was 98%, with 89% of patients reporting levels of satisfaction with the reconstructed breast, of excellent, very good, or good. We evaluated that 70 of the 193 procedures could have been performed as nipple-sparing mastectomy (NSM). CONCLUSIONS: The outcomes of SSM in this series were excellent and NSM might have been an option for about one-third of the patients.

Breast metastasis nine years after nephrectomy for renal cell carcinoma: A case report.

INTRODUCTION: The breast is a rare site for metastatic disease. We report a rare case of breast metastasis 9 years after nephrectomy for renal cell carcinoma (RCC) and include a review of the relevant literature. PRESENTATION OF CASE: An 82-year-old woman who developed an RCC underwent left nephrectomy in 2005. In October 2014, computed tomography (CT) revealed a mass of approximately 1cm in the lateral portion of the right breast. Breast ultrasonography (US) revealed a well-circumscribed, hypoechoic mass at the same site. Fine needle aspiration (FNA) was performed, but the sample was inadequate because it did not capture breast duct epithelial cells. In June 2015, follow-up US revealed enlargement of the mass, and core needle biopsy (CNB) was performed to confirm the diagnosis. Histological examination resulted in the diagnosis of breast metastasis from an RCC. The patient underwent surgery for partial mastectomy in November 2015. The patient was asymptomatic and free of detectable disease at 18-month follow-up. DISCUSSION: The diagnosis of breast metastasis by imaging examination is difficult, and the results of FNA examination are often inconclusive because of the absence of breast duct epithelial cells. Only 22 cases of breast metastasis from RCC have been described in the literature. In almost all the reported cases, lumpectomy or partial mastectomy was performed. CONCLUSION: It is important that histological diagnosis be determined by CNB and by other methods if the patient has a history of malignancy, and minimally invasive therapy should be performed in accordance with the prognosis.