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.

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.

A new rabbit model of impaired wound healing in an X-ray-irradiated field.

Radiation is an important therapy for cancer with many benefits; however, its side effects, such as impaired wound healing, are a major problem. While many attempts have been made to overcome this particular disadvantage, there are few effective treatments for impaired wound healing in an X-ray-irradiated field. One reason for this deficiency is the lack of experimental models, especially animal models. We have previously reported a mouse model of impaired wound healing in which the irradiation area was restricted to the hindlimbs. In this mouse model, due to the size of the animal, a diameter of five millimeters was considered the largest wound size suitable for the model. In addition, the transplanted cells had to be harvested from other inbred animals. To investigate larger wounds and the impact of autologous specimen delivery, a rabbit model was developed. Rabbits were kept in a special apparatus to shield the body and hindlimbs while the irradiation field was exposed to radiation. Six weeks after irradiation, a 2 x 2 cm, full-thickness skin defect was made inside the irradiation field. Then, the wound area was observed over time. The wound area after irradiation was larger than that without irradiation at all time points. Both angiogenesis and collagen formation were reduced. For further study, as an example of using this model, the effect of autologous platelet-rich plasma (PRP) was observed. Autologous PRP from peripheral blood (pb-PRP) and bone marrow aspirate (bm-PRP) was processed and injected into the wounds in the irradiated field. Two weeks later, the wounds treated with bm-PRP were significantly smaller than those treated with phosphate buffer vehicle controls. In contrast, the wounds treated with pb-PRP were not significantly different from the controls. This rabbit model is useful for investigating the mechanism of impaired wound healing in an X-ray-irradiated field.

Free flap transfer reconstruction in managing tongue carcinoma during pregnancy.

Malignant oral cancers do not commonly occur in pregnant women. But when they do, the presence of a foetus and maternal physiological changes complicate and limit the treatment options. Risk benefit assessment and balancing of them are always important. A 33-year-old woman, who was 25 weeks pregnant, presented with a squamous cell carcinoma on her tongue. She was clinically staged II (T2, N0 and M0). Discussions between the patient, surgical teams and obstetricians agreed to continue her pregnancy while managing the tumour. Hemi-glossectomy and ipsilateral neck dissection was performed. Free antero-lateral thigh flap was transferred to reconstruct the tongue defect, successfully. The patient gave birth to a healthy baby afterward. She is tumour free for 6 years. Free flap reconstruction can be an option, even if the patient is pregnant.

Congenital lipomatous tumour, presented as a polypoidal projection on upper eyelid.

A Japanese baby was born with a polypoidal projection with hair, on the lateral corner of upper eyelid. The tumour had extent to bulbar sub-conjunctival area. He presented no other malformation nor pathological symptoms. There was no sign of association with Goldenhar, hemifacial macrosomia, epidermal nevus or linear nevus sebaceous syndromes. The tumour was resected at his age of 4 months. The ocular conjunctiva was incised but not excised. Histopathologically, it was mainly consisted of multi-lobuled mature adipose tissue, dense fibrous tissue was observed at the centre of mass, assumed to be the link of palpebral tarsal plate to lateral canthal ligament. As for the location and component, the tumour was diagnosed as a lipomatous hamartoma. Detached tarsal plate was reattached to the lateral canthal ligament. Satisfactory result was achieved aesthetically and functionally. Congenital lipomatous hamartoma, with protuberant appendage appearance on eyelid, without syndromic association, is presented.

Bilateral Maxillary Reconstruction Using Fibular Flap in Bisphosphonate-related Osteonecrosis.

Recent reports have shown successful transfer of vascularized fibular flap in bisphosphonate-induced mandibular osteonecrosis. We present a case of a 50-year-old patient who presented with bisphosphonate-related osteonecrosis of bilateral maxilla, which is reconstructed using a fibular flap.

Lymphoedema of the penis and scrotum as a sequela of chronic skin infection.

A Japanese male patient presented with an enormously disfigured penis and scrotum. The penis was swollen and distorted rightward, and the skin was hard and lumpy. The patient had had a subdermal abscess for 6 years. The current condition was considered secondary lymphoedema of the penis and scrotum resulting from chronic skin infection. Wide excision of the affected area with bilateral inguinal lymph node dissection were performed. The degloved penile shaft and scrotum were covered with skin grafts, and a satisfactory result was obtained.

An augmented reality system in lymphatico-venous anastomosis surgery.

Indocyanine green lymphography, displayed as infrared image, is very useful in identifying lymphatic vessels during surgeries. Surgeons refer the infrared image on the displays as they proceed the operation. Those displays are usually placed on the walls or besides the operation tables. The surgeons cannot watch the infrared image and the operation field simultaneously. They have to move their heads and visual lines. An augmented reality system was developed for simultaneous referring of the infrared image, overlaid on real operation field view. A surgeon wore a see-through eye-glasses type display during lymphatico-venous anastomosis surgery. Infrared image was transferred wirelessly to the display. The surgeon was able to recognize fluorescently shining lymphatic vessels projected on the glasses and dissect them out.

Growth Factor Measurement and Histological Analysis in Platelet Rich Fibrin: A Pilot Study.

OBJECTIVE: The aim of this study was to compare growth factor amount contained in platelet rich fibrin (PRF) and compare with that in platelet rich plasma (PRP), and in whole blood. And also to investigate distribution of growth factors and cellular components in PRF. MATERIALS AND METHODS: PRF and PRP were obtained from the same sample of peripheral blood. Extraction of proteins were done with lysis buffer, accompanied by freeze and thaw procedures. Concentration of two representative growth factors in platelets: platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-ß), were measured with enzyme-linked immunosorbent assay (ELISA). PRF was cut into three parts: (top, middle and bottom), and growth factor concentration was measured respectively. Paraffin embedded section of PRF was observed with Giemsa stain. Immuno-histochemical analysis with anti-PDGF and anti-TGF-ß antibodies was also conducted. RESULTS: The growth factor levels in PRF was higher than in peripheral blood and comparable to those in PRP. Growth factor levels in bottom part of PRF was much higher than in top and middle part. Microscopically, platelets and mono-nucleated cells were concentrated just above the yellow-red interface. Poly-nucleated cells were concentrated below the interface. CONCLUSION: The growth factors were surely concentrated in PRF. This result can support basis of good clinical outcomes. For effective application of PRF, the knowledge that growth factors and cells are not equally distributed in PRF should be utilized.

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.

End-to-side "loop" graft for total facial nerve reconstruction: Over 10 years experience.

BACKGROUND: Multiple-branch reconstruction is required in order to attain facial reanimation for extensive facial nerve defects. We previously reported that end-to-side nerve grafting, with the use of a single nerve graft for defect reconstruction, was easy to perform. We have also demonstrated the efficacy of end-to-side nerve suture of the recipient nerve to the donor graft nerve, in experimental rat models and clinical cases. The regenerating axons, which extended into the nerve graft, were "distributed" to multiple recipient nerves via end-to-side nerve-suture sites. METHODS: Thirty-two patients who underwent facial nerve reconstruction (five to 10 branches) had a single sural nerve graft coapted to the proximal stump of the facial nerve in an end-to-end manner, followed by end-to-side nerve suture of the recipient nerve stumps to the side of the nerve graft. In 19 patients who were expected to undergo postoperative radiotherapy and/or chemotherapy, the distal end of the graft was connected to the side of the hypoglossal nerve for "axonal supercharging," to enhance the recovery of the facial muscles. RESULTS: Initial facial movements were noted at 5-12 months postoperatively, and good recovery (House-Brackmann grade III/IV) was observed during long-term follow-up in most patients. CONCLUSION: End-to-side nerve suture of the recipient nerve stumps to the nerve graft requires less graft nerve material and less technical mastery to reconstruct multiple branches of the facial nerve. We also described the concept of "axonal supercharging," namely the connection of double-donor neural sources to the graft, and "axonal distribution," namely the reinnervation of multiple recipient nerve stumps connected to the graft in an end-to-side manner. This combination of axonal supercharging and distribution can be a useful option in facial nerve reconstruction.