Surgical Correction of Nipple Hypertrophy after Nipple-sparing Mastectomy with Breast Reconstruction.

Nipple hypertrophy is a relatively common phenomenon, particularly in the Asian patient population. The incidence and prevalence or cause of nipple hypertrophy are not well defined in the literature. As survival rates for breast cancer patients continue to improve, there is an increasing emphasis on enhancing their quality of life. Treatment options, such as lumpectomy and radiation therapy or mastectomy, now prioritize preservation of the nipple-areolar complex (NAC) through techniques like nipple-sparing mastectomy (NSM). This approach has been shown to improve patient satisfaction and quality of life. However, it is important to note that NSM is associated with certain complications, including NAC necrosis, malposition, and local recurrence of the tumor. Among those complications, nipple hypertrophy is quite rare. In this report, we present a case of nipple hypertrophy that developed after breast reconstruction, using autologous tissue. The patient, a 48-year-old woman, underwent NSM for breast cancer, and had a tissue expander placed simultaneously. Following tissue expansion, breast reconstruction with a deep inferior epigastric perforator (DIEP) flap was performed. However, during the tissue expansion phase, the patient's nipple gradually enlarged, and the protrusion became more pronounced after the DIEP flap transfer. Nipple reduction surgery was subsequently performed for both diagnostic and cosmetic purposes. We present this case along with a review of relevant literature.

Three-Dimensional Craniofacial Landmark Detection in Series of CT Slices Using Multi-Phased Regression Networks.

Geometrical assessments of human skulls have been conducted based on anatomical landmarks. If developed, the automatic detection of these landmarks will yield both medical and anthropological benefits. In this study, an automated system with multi-phased deep learning networks was developed to predict the three-dimensional coordinate values of craniofacial landmarks. Computed tomography images of the craniofacial area were obtained from a publicly available database. They were digitally reconstructed into three-dimensional objects. Sixteen anatomical landmarks were plotted on each of the objects, and their coordinate values were recorded. Three-phased regression deep learning networks were trained using ninety training datasets. For the evaluation, 30 testing datasets were employed. The 3D error for the first phase, which tested 30 data, was 11.60 px on average (1 px = 500/512 mm). For the second phase, it was significantly improved to 4.66 px. For the third phase, it was further significantly reduced to 2.88. This was comparable to the gaps between the landmarks, as plotted by two experienced practitioners. Our proposed method of multi-phased prediction, which conducts coarse detection first and narrows down the detection area, may be a possible solution to prediction problems, taking into account the physical limitations of memory and computation.

Stretching Promotes Wound Contraction Through Enhanced Expression of Endothelin Receptor B and TRPC3 in Fibroblasts.

One factor that can contribute to the development of hypertrophic scar contracture is mechanical stress. Mechanical cyclic stretch stimuli enhance the secretion of endothelin-1 (ET-1) from keratinocyte. Cyclical stretching of fibroblasts also increases the expression level of the transient receptor potential ion channel (TRPC3), which is known to couple with the endothelin receptor and induce intracellular Ca2+ signaling via the calcineurin/nuclear factor of activated T cells (NFAT) pathway. The aim of this study was to investigate the relationship between keratinocytes and fibroblasts when they are stretched. Methods: The conditioned medium from stretched keratinocyte was added to the fibroblast populated collagen lattice. Then, we analyzed the levels of endothelin receptor in the human hypertrophic scar tissue and stretched fibroblasts. To address the function of TRPC3, we have used an overexpression system with the collagen lattice. Finally, the TRPC3 overexpressing fibroblasts were transplanted to mouse dorsal skin, and the rate of skin wound contraction was assessed. Results: Conditioned medium from stretched keratinocytes increased the rate of contraction of fibroblast populated collagen lattice. In human hypertrophic scar and stretched fibroblasts, endothelin receptor type B was increased. Cyclic stretching of TRPC3 overexpressing fibroblasts activated NFATc4, and stretched human fibroblasts showed more activation of NFATc4 in response to ET-1. The wound treated with TRPC3 overexpressing fibroblasts showed more contraction than control wound. Conclusion: These findings suggest that cyclical stretching of wounds have an effect on both keratinocytes and fibroblasts, where keratinocytes secret more ET-1, and fibroblasts develop more sensitivity to ET-1 by expressing more endothelin receptors and TRPC3.

Cutaneous fistula on the cheek associated with oculo-auriculo-vertebral spectrum.

A Japanese boy, presented with epibulbar dermoid and ipsilateral preauricular appendages, had a pit on his cheek of the same side. An atrial septal defect and vertebral fusions were also identified. He was diagnosed with a mild type of oculo-auriculo-vertebral spectrum (OAVS). At the age of 18 months, his cheek was swollen with a slight fever. An infected cyst and cutaneous fistula enveloped by the risorius muscle were extracted. It was assumed to be a remnant of the fissure between the maxillary and mandibular prominences. This was the first case of cutaneous fistula confirmed histologically with OAVS, although there seem to be more cases. The possibility of the mechanism of smiling cheek dimple is also discussed.

A traumatic ulnar artery aneurysm in an infant.

Ulnar artery aneurysm is very rare in infancy. Only a few reports have been done. We report an 8-month-old baby with true ulnar artery aneurysm on her hypothenar eminence. She had no specific past medical history, but an episode of falling. We resected the pulsating mass compressing the ulnar nerve, utilizing a surgical microscope. Reconstruction of the vascular deficit was not performed. She presented no functional deficit of the hand and no evidence of growth disturbance so far. As hypothenar eminence is a susceptible part for repetitive strikes, and as vein is fragile to the pressure, bypassing arterial route with vein graft is not recommended unless there is no other option.

An occult case of the first branchial cleft anomaly.

We report a case of the first branchial cleft anomaly, clinically typical but occult in images and pathology. An 8-year-old female who had an induration below her right mandibular angle was referred to our department with a diagnosis of an infectious epidermal cyst. CT and MRI had shown no evidence of fistula or cyst. At the initial operation, a string structure was observed, but pathologically no epithelial structure was observed. However, the infection at the same site repeated and the symptoms became more severe than before. Considering a high probability of the first branchial anomaly, partial parotidectomy was performed as radical surgery. A cord structure attached to subcutaneous tissue at the intertragal notch was found. Although no epithelial component in the pathology was detected, this string structure was clinically considered as the rudimentary form of the first branchial anomaly.

Personal Computer-Based Cephalometric Landmark Detection With Deep Learning, Using Cephalograms on the Internet.

BACKGROUND: Cephalometric analysis has long been, and still is one of the most important tools in evaluating craniomaxillofacial skeletal profile. To perform this, manual tracing of x-ray film and plotting landmarks have been required. This procedure is time-consuming and demands expertise. In these days, computerized cephalometric systems have been introduced; however, tracing and plotting still have to be done on the monitor display. Artificial intelligence is developing rapidly. Deep learning is one of the most evolving areas in artificial intelligence. The authors made an automated landmark predicting system, based on a deep learning neural network. METHODS: On a personal desktop computer, a convolutional network was built for regression analysis of cephalometric landmarks' coordinate values. Lateral cephalogram images were gathered through the internet and 219 images were obtained. Ten skeletal cephalometric landmarks were manually plotted and coordinate values of them were listed. The images were randomly divided into 153 training images and 66 testing images. Training images were expanded 51 folds. The network was trained with the expanded training images. With the testing images, landmarks were predicted by the network. Prediction errors from manually plotted points were evaluated. RESULTS: Average and median prediction errors were 17.02 and 16.22 pixels. Angles and lengths in cephalometric analysis, predicted by the neural network, were not statistically different from those calculated from manually plotted points. CONCLUSION: Despite the variety of image quality, using cephalogram images on the internet is a feasible approach for landmark prediction.

Fibrous dysplasia and Klippel-Trenaunay syndrome: a rare association.

Fibrous dysplasia is a rare congenital disorder, with abnormal hypertrophy of affected bone. A 17-year-old girl with a protrusion on her right forehead presented and was diagnosed as craniofacial fibrous dysplasia. Although she had no gait problem, her right leg was longer than the other. She had vascular malformation on the right leg. The condition was diagnosed as Klippel-Trénaunay syndrome, which also is a rare disorder. As the prevalence of these disorders is scarce, the probability of coincidental association of them is extremely low. No previous report about the association of fibrous dysplasia and Klippel-Trénaunay syndrome could be found. We concluded that, those two rare congenital disorders arose coincidentally in this patient.

An Attempt to Make Platelet Rich Fibrin from Bone Marrow Aspirate.

INTRODUCTION: Platelet Rich Fibrin (PRF) was developed as a new generation of platelet concentration from peripheral blood. Method to make PRF is simple. It is easy to handle with its moderate firmness. Histologically, platelets and nucleated cells are packed along the yellow-red border. Bone marrow aspirate contains bone marrow cells that potentially work for tissue regeneration, and platelets which contain growth factors. The specific gravities of them are comparable. It implies that, if it is possible to make PRF from bone marrow aspirate, then high concentration of platelets and bone marrow cells can be obtained simultaneously by taking out yellow-red interface of it. AIM: To find out a method to make PRF from bone marrow aspirate. MATERIALS AND METHODS: Iliac crest of rabbits were punctured and aspirated with or without anti-coagulant, under general anaesthesia. The bone marrow aspirate was centrifuged in glass tubes. For the bone marrow aspirate taken with anti-coagulant, calcium chloride was added just before centrifugation. Products were taken out and observed grossly. The products were fixed with formaldehyde and observed histologically. RESULTS: Coagulated gels with two-toned colour were obtained by all methods. In the gels without anti-coagulant, interfaces between two colours were obscure. Histologically, platelets and nucleated cells scattered as clusters. Filtering caused haemolysis and reduced the yield of the product. With the aspirate taken with anti-coagulant, platelets and nucleated cells formed a band along the interface. CONCLUSION: PRF can be made from bone marrow aspirate by adding anti-coagulant in aspiration and reversed with calcium chloride just before centrifugation.

Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation.

Wound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring.

The dawn of computer-assisted robotic osteotomy with ytterbium-doped fiber laser.

Currently, laser radiation is used routinely in medical applications. For infrared lasers, bone ablation and the healing process have been reported, but no laser systems are established and applied in clinical bone surgery. Furthermore, industrial laser applications utilize computer and robot assistance; medical laser radiations are still mostly conducted manually nowadays. The purpose of this study was to compare the histological appearance of bone ablation and healing response in rabbit radial bone osteotomy created by surgical saw and ytterbium-doped fiber laser controlled by a computer with use of nitrogen surface cooling spray. An Ytterbium (Yb)-doped fiber laser at a wavelength of 1,070 nm was guided by a computer-aided robotic system, with a spot size of 100 µm at a distance of approximately 80 mm from the surface. The output power of the laser was 60 W at the scanning speed of 20 mm/s scan using continuous wave system with nitrogen spray level 0.5 MPa (energy density, 3.8 × 10(4) W/cm(2)). Rabbits radial bone osteotomy was performed by an Yb-doped fiber laser and a surgical saw. Additionally, histological analyses of the osteotomy site were performed on day 0 and day 21. Yb-doped fiber laser osteotomy revealed a remarkable cutting efficiency. There were little signs of tissue damage to the muscle. Lased specimens have shown no delayed healing compared with the saw osteotomies. Computer-assisted robotic osteotomy with Yb-doped fiber laser was able to perform. In rabbit model, laser-induced osteotomy defects, compared to those by surgical saw, exhibited no delayed healing response.

Influence of continuous or intermittent negative pressure on bacterial proliferation potency in vitro.

Negative pressure wound therapy is helpful and effective in the treatment of intractable skin ulcers and defects, not only acute wounds. However, application of negative pressure wound therapy for an infected wound is still controversial. The authors developed an in-vitro model of negative pressure wound therapy and investigated the influence of various types of negative pressure environment on the proliferation potency of non-pathogenic Escherichia coli. E. coli in Luria-Bertani liquid media was cultured at 37°C under different environments, which were normal atmosphere in group 1, continuous negative pressure of 75 mmHg in group 2, intermittent negative pressure of 75 mmHg with cycle time of 1 minute aspiration and 1 minute abeyance in group 3, with the one of 3 minutes aspiration and 3 minutes abeyance in group 4. The relative amounts of E. coli in each group were investigated at different times. The proliferation potency of E. coli was higher under negative pressure than under normal atmosphere; higher under intermittent negative pressure than under continuous negative pressure; and higher under intermittent negative pressure with a short cycle than with a long cycle. It is important to consider the possibility that the intermittent and continuous mode of negative pressure wound therapy may promote proliferation of bacteria in an infected wound with no blood flow like necrotic tissue.

A new mouse model of impaired wound healing after irradiation.

Radiation has many benefits and is an important treatment for cancer therapy. However, it also has unfavourable side-effects. Among these side-effects, the impairment of wound healing in the skin is a major problem in clinics. Although many attempts have been made to overcome this shortcoming, there are few effective treatments for impaired wound healing after irradiation. One reason for this is that it is hard to obtain good animal models for researching this topic. In this study, two different models were created and investigated. In one model, rectangular flaps were created on the backs of mice and irradiated while the other parts of their bodies were covered with a lead board. In another model, the lower limbs were exposed to radiation. In each model, several doses of irradiation were tested. Skin ulcers were created in the irradiated area, and the wound healing process was observed. In order to verify the usefulness of the model, adipose derived stromal cells were injected into the wound and the healing rate was calculated. In the flap model, the flaps contracted and formed linear scars. On the other hand, in the thigh model, 15 Gy irradiation resulted in slow wound healing but no strong inflammation or necrosis. The transplantation of adipose tissue derived stromal cells into the irradiated thigh wound improved the wound healing. This study suggested that irradiation of the lower limb at ∼ 15 Gy might be an appropriate model for basic research into wound healing in irradiated skin.

Comparative study of the antibacterial penetrating effects of wound dressings.

In an infected wound, bacteria are present not only on the surface but also within the granulation tissue. The presence of bacteria inside the granulation tissue is one of the reasons for our inability to control infection. We have developed an in vitro model of an infected wound using Luria-Bertani (LB) agar media and non-pathogenic Escherichia coli, and compared the differences in the antibacterial effects of various types of antibacterial wound dressings. The results have shown that the penetrating antibacterial effects differed according to the type of wound dressing selected. As the thickness of the layer of the LB agar media increased, the potency of antibacterial effects caused by penetration decreased. In conclusion, it was suggested that antibacterial wound dressings can have antibacterial effects against bacteria not only on the surface of an infected wound but inside, so it is necessary to use different wound dressings according to the conditions of each infected wound.

Calcium-based nanoparticles accelerate skin wound healing.

INTRODUCTION: Nanoparticles (NPs) are small entities that consist of a hydroxyapatite core, which can bind ions, proteins, and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calcium levels and have the potential to modulate calcium homeostasis in vivo. Nanoparticles have been associated with various calcium-mediated disease processes, such as atherosclerosis and kidney stone formation. We hypothesized that nanoparticles could have an effect on other calcium-regulated processes, such as wound healing. In the present study, we synthesized pH-sensitive calcium-based nanoparticles and investigated their ability to enhance cutaneous wound repair. METHODS: Different populations of nanoparticles were synthesized on collagen-coated plates under various growth conditions. Bilateral dorsal cutaneous wounds were made on 8-week-old female Balb/c mice. Nanoparticles were then either administered intravenously or applied topically to the wound bed. The rate of wound closure was quantified. Intravenously injected nanoparticles were tracked using a FLAG detection system. The effect of nanoparticles on fibroblast contraction and proliferation was assessed. RESULTS: A population of pH-sensitive calcium-based nanoparticles was identified. When intravenously administered, these nanoparticles acutely increased the rate of wound healing. Intravenously administered nanoparticles were localized to the wound site, as evidenced by FLAG staining. Nanoparticles increased fibroblast calcium uptake in vitro and caused contracture of a fibroblast populated collagen lattice in a dose-dependent manner. Nanoparticles also increased the rate of fibroblast proliferation. CONCLUSION: Intravenously administered, calcium-based nanoparticles can acutely decrease open wound size via contracture. We hypothesize that their contraction effect is mediated by the release of ionized calcium into the wound bed, which occurs when the pH-sensitive nanoparticles disintegrate in the acidic wound microenvironment. This is the first study to demonstrate that calcium-based nanoparticles can have a therapeutic benefit, which has important implications for the treatment of wounds.