Cardiac overload resolved by resection of a large plexiform neurofibroma on both the buttocks and upper posterior thighs in a patient with neurofibromatosis type I: a case report.

BACKGROUND: A large plexiform neurofibroma in patients with neurofibromatosis type I can be life threatening due to possible massive bleeding within the lesion. Although the literature includes many reports that describe the plexiform neurofibroma size and weight or strategies for their surgical treatment, few have discussed their possible physical or mental benefits, such as reducing cardiac stress. In addition, resection of these large tumors can result in impaired wound healing, partly due to massive blood loss during surgery. CASE PRESENTATION: A 24-year-old man was diagnosed with neurofibromatosis type I and burdened with a large plexiform neurofibroma on the buttocks and upper posterior thighs. The patient was 159 cm in height and 70.0 kg in weight at the first visit. Cardiac overload was indicated by an echocardiography before surgery. His cardiac output was 5.2 L/min with mild tricuspid regurgitation. After embolism of the arteries feeding the tumor, the patient underwent surgery to remove the neurofibroma, followed by skin grafting. Follow-up echocardiography, performed 6 months after the final surgery, indicated a decreased cardiac output (3.6 L/min) with improvement of tricuspid regurgitation. Because the blood loss during the first surgery was over 3.8 L, malnutrition with albuminemia was induced and half of the skin graft did not attach. Nutritional support to improve the albuminemia produced better results following a second surgery to repair the skin wound. CONCLUSION: Cardiac overload may be latent in patients with neurofibromatosis type I with large plexiform neurofibromas. As in pregnancy, the body may compensate for this burden. In these patients, one stage total excision may improve quality of life and reduce cardiac overload. In addition, nutritional support is likely needed following a major surgery that results in either an extensive skin wound or excessive blood loss during treatment.

Negative Pressure Wound Therapy Followed by Basic Fibroblast Growth Factor Spray as a Recovery Technique in Partial Necrosis of Distally Based Sural Flap for Calcaneal Osteomyelitis: A Case Report.

The distally based sural flap is regarded as the first choice for reconstruction in the distal part of the lower leg because the flap is easy to raise, reliable in its blood supply, and prone to only a few complications. Limited data have investigated the details of treatment in cases of failure of distally based sural flaps. We report a case of calcaneal osteomyelitis in which a successful outcome was finally obtained with a partially necrosed, distally based sural flap using negative pressure wound therapy with basic fibroblast growth factor spray. The 2-year follow-up examination was uneventful. Moreover, the patient was able to walk freely with an ankle-foot orthosis in her house. This technique can be considered as a useful and effective option to recover unfavorable results of distally based sural flaps.

Deltopectoral flap revisited for reconstruction surgery in patients with advanced thyroid cancer: a case report.

BACKGROUND: We present the cases of 2 patients with invasive thyroid cancer, who underwent reconstructive surgery using a deltopectoral flap. Although the overall rate of extrathyroidal extension in patients with thyroid cancer is quite low, skin invasion is the most common pattern observed. Reconstructive surgery, involving local skin flaps, is required in these patients. The deltopectoral flap relies on the blood supply from intercostal perforators of the internal thoracic artery and usually requires skin grafting to the donor site. The internal thoracic artery is rarely sacrificed in these cases, even in an advanced surgery such as in patients with invasive thyroid cancer. CASE PRESENTATION: A 55-year-old man with a distended thyroid gland presented to our hospital. He underwent advanced surgery, including skin excision, because we suspected that his tumor was thyroid cancer. The defect was covered with an ipsilateral deltopectoral flap via transposition of the flap, without skin grafting. In the second case, a 67-year-old woman with thyroid cancer that metastasized to her neck lymph nodes presented to our institution. Although the ipsilateral internal thoracic artery was sacrificed near its origin during tumor resection, the deltopectoral flap was raised in the usual manner without any complications. The skin defect caused by the tumor resection was covered with the flap. The patient had an uneventful clinical course for more than 2 years of follow-up. These 2 cases show the effectiveness of using the deltopectoral flap as a reconstructive option for patients with thyroid cancer who underwent radical surgery, resulting in a skin defect. The first case shows that this flap does not always require skin grafting to the donor site. To our knowledge, the second case may be the first report of a deltopectoral flap that was safely raised and applied with resection of the bifurcation of the ipsilateral internal thoracic artery. CONCLUSIONS: Although thyroid cancer surgery with surrounding skin excision is a rare procedure, we found that the deltopectoral flap was useful and should be the first choice for patients undergoing reconstructive surgery, whether the bifurcation of the ipsilateral internal thoracic artery is sacrificed.

Inhibition of Rho-associated kinases disturbs the collective cell migration of stratified TE-10 cells.

BACKGROUND: The collective cell migration of stratified epithelial cells is considered to be an important phenomenon in wound healing, development, and cancer invasion; however, little is known about the mechanisms involved. Furthermore, whereas Rho family proteins, including RhoA, play important roles in cell migration, the exact role of Rho-associated coiled coil-containing protein kinases (ROCKs) in cell migration is controversial and might be cell-type dependent. Here, we report the development of a novel modified scratch assay that was used to observe the collective cell migration of stratified TE-10 cells derived from a human esophageal cancer specimen. RESULTS: Desmosomes were found between the TE-10 cells and microvilli of the surface of the cell sheet. The leading edge of cells in the cell sheet formed a simple layer and moved forward regularly; these rows were followed by the stratified epithelium. ROCK inhibitors and ROCK small interfering RNAs (siRNAs) disturbed not only the collective migration of the leading edge of this cell sheet, but also the stratified layer in the rear. In contrast, RhoA siRNA treatment resulted in more rapid migration of the leading rows and disturbed movement of the stratified portion. CONCLUSIONS: The data presented in this study suggest that ROCKs play an important role in mediating the collective migration of TE-10 cell sheets. In addition, differences between the effects of siRNAs targeting either RhoA or ROCKs suggested that distinct mechanisms regulate the collective cell migration in the simple epithelium of the wound edge versus the stratified layer of the epithelium.

Lipoprotein Apheresis Alleviates Treatment-Resistant Peripheral Artery Disease Despite the Normal Range of Atherogenic Lipoproteins: The LETS-PAD Study.

AIM: Peripheral artery disease (PAD) severely impairs patient prognosis and quality of life (QOL). Although lipoprotein apheresis (LA) has been applied to patients with PAD and elevated serum atherogenic lipoproteins, we hypothesized that LA can be effective for treating PAD even in patients with controlled serum lipoproteins through pleiotropic anti-atherosclerotic effects beyond lipoprotein removal. This study aimed to evaluate the efficacy of LA in patients with treatment-resistant PAD and controlled serum lipoproteins focusing on QOL. METHODS: In a single-arm prospective study, 30 patients with refractory PAD who had controlled serum lipoproteins underwent sequential LA sessions using dextran sulfate adsorption columns, aiming to complete 10 sessions. The ankle-brachial pressure index (ABI) and vascular QOL (VascuQOL) score were evaluated as the primary outcomes. Secondary outcomes included reactive hyperemia index (RHI) and biological antioxidant potential (BAP) as an endothelial function test and serum antioxidative-capacity evaluation, respectively. RESULTS: ABI significantly increased after LA sessions (pre-treatment 0.60±0.09 vs. post-treatment 0.65±0.13, p=0.023). Total VascuQOL score (3.7±1.1 vs 4.6±1.1, p＜0.001) and RHI (1.70±0.74 vs 2.34±1.76, p=0.023) significantly improved after the LA sessions. BAP tended to increase after the LA sessions, and the change reached statistical significance 3 months after treatment. CONCLUSION: ABI and QOL improved after a series of LA sessions in conventional treatment-resistant PAD patients with controlled serum lipoprotein levels. Increased antioxidative capacity and ameliorated endothelial function were observed after the LA treatment.

Recurrent endocrine mucin-producing sweat gland carcinoma in the eyelid.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) has recently been recognised as a low-grade carcinoma that almost always occurs on the eyelid. This carcinoma is very rare, with only 20 cases (including the present one) having been reported in the literature. EMPSGC is frequently found in association with invasive mucinous carcinoma. While EMPSGC treatments consist of a complete surgical removal, there has been no consensus regarding the surgical margin. Therefore, reports on surgical management of EMPSGC may potentially provide important therapeutic information. Here, we present a case of a 74-year-old man with EMPSGC of the eyelid that repeatedly recurred despite surgical treatments at another institution. After referral to our department, the patient underwent tumour excision. However, the specimen revealed a positive surgical margin and thus, he subsequently underwent a wider excision. There has been no sign of tumour recurrence or metastasis 6 months after his last operation. This article reviews the current literature and discusses the surgical management of EMPSGC.

Isolation of multipotent nestin-expressing stem cells derived from the epidermis of elderly humans and TAT-VHL peptide-mediated neuronal differentiation of these cells.

A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy.

Pectoralis Major Myocutaneous Flap Revisited as a Workhorse for Reconstruction for Defects in the Upper Arm: A Case Report.

Many previous reviews of the literature have described the grafts and techniques for management of defects in the upper arm. However, the alternatives are limited in cases where some conventional flaps are not available and the nearby donor vessels have been previously sacrificed for free flaps. A 77-year-old man presented with a tumor in the right upper arm just above the axilla. The patient had already undergone surgeries for three recurrences of low-grade myxofibrosarcoma, the primary site of which was around the right scapula. The pectoralis major musculocutaneous flap was used for the defect caused by tumor resection, since there was no other available option. An acceptable result was obtained without any major complications. Thus, the pectoralis major myocutaneous flap may be a candidate for reconstruction of defects in the proximal part of the upper arm.

Plasmodium induced by SU6656, an Src family kinase inhibitor, is accompanied by a contractile ring defect.

We have shown that SU6656, a potent Src family kinase inhibitor, has the ability to induce multinucleation at a high frequency in diverse cells: rat skin fibroblasts, bone marrow adherent cells, 5F9A mesenchymal stem cell-like clones, 2C5 tracheal epithelial cells and MDCK epithelial cells from dog kidney. To gain insight into the mechanism of multinucleation, we observed the process by time-lapse and confocal microscopy. These multinuclei generally seem to exist independently in one cell without any connections with each other. By time-lapse microscopy, multinucleated cells were found to be formed through the mechanism of plasmodium: karyokinesis without cytokinesis. The observation of EGFP-actin transfected cells by time-lapse confocal laser scanning microscopy suggested that plasmodium occurred with deficient contractile ring formation. Although we examined the differentiation of these cells, the multinucleated cells could not be categorized into any type of cell in vivo known to exhibit multinuclei.

Subacute phase treatment of subperiosteal hematoma of the orbit with epidural hematoma in the frontal cranial fossa: case report.

BACKGROUND: Subperiosteal hematoma of the orbit is one of the rare lesions that cause exophthalmos after craniomaxillofacial trauma. Presently, there is no consensus for how to treat this disease. Although some reports have suggested a conservative type of therapy, others have recommended surgical treatments be done during the early stages. CASE PRESENTATION: This case report provides details on the clinical course of a 9-year-old girl with subperiosteal hematoma of the orbit. In this particular patient, a rare case of ipsilateral subfrontal extradural hematoma was also observed. Due to our performing the surgical intervention during the subacute stage, functional complications as well as cosmetic problems were avoided. CONCLUSION: Our results demonstrate that surgical treatments for subperiosteal hematoma of the orbit should be delayed until it can be confirmed that a patient has no other complications. On the other hand, once it has been confirmed that the patient has no other existing problems, immediate surgical therapy with a small skin incision followed by the setting of a drain is recommended in order to achieve an early resolution and avoid complications.

Pathological Changes in the Lymphatic System of Patients with Secondary Lower Limb Lymphedema Based on Single Photon-Emission Computed Tomography/Computed Tomography/Lymphoscintigraphy Images.

Background: In patients with secondary upper limb lymphedema, positive correlations have been observed between the dermal back flow (DBF) type and visualization of lymph nodes around the clavicle, between the former and the lymph flow pathway type, and between the latter and the visualization of lymph nodes around the clavicle when using single photon-emission computed tomography/computed tomography/lymphoscintigraphy (SPECT-CT LSG). Methods and Results: We analyzed the associations between the visualization of inguinal lymph nodes, the lymph flow pathway type, and the DBF type using SPECT-CT LSG in 81 patients with unilateral secondary lower limb lymphedema by statistical analysis using Fisher's exact test. We revealed that the lymph flow pathways in the lower limb can be classified into nine types because the type in the lower leg is not always equal to the type in the thigh. Associations were observed between the visualization of inguinal lymph nodes and types of DBF (p < 0.01), between the types of lymph flow pathway in the thighs and visualization of the inguinal lymph nodes (p = 0.02), and between the lymph flow pathway types in the thighs and lower legs (p < 0.01). Conclusion: Detriment to the superficial lymph flow pathways in the lower limb appears to usually start from the proximal side, and deep pathways are considered to become dominant from a compensatory perspective as lymphedema severity increases.

A Novel Approach to Subcutaneous Collecting Lymph Ducts Using a Small Diameter Wire in Animal Experiments and Clinical Trials.

Background: While performing microsurgery, including lymphaticovenous anastomosis (LVA) for chronic limb lymphedema, it is a common procedure to identify the subcutaneous collecting lymph ducts with near-infrared fluorescence lymphangiography (NIR) using indocyanine green. However, due to limitations such as minimum observable depth, only a few lymphatic ducts can be identified with this procedure. Hence, we developed a new smaller-diameter "lymphatic wire" (LW) that could be inserted directly into lymphatic collecting ducts of the limbs, enabling accurate identification and localization. Methods and Results: First, used the LW on the hind limbs of 6 swine, and 36 porcine lymphatic collecting ducts were identified, the outer diameter of which varied from 0.3-0.7 mm (mean 0.41 ± 0.11 mm). We could insert the LW after creating a side opening in 30 of these ducts. We encountered no difficulties during the procedure. In the pathological examination, adverse events such as valve dysfunction and perforation were not identified. Based on the results, a clinical evaluation of the LW was performed in two patients with lower extremity lymphedema, and the LW helped us identify lymphatic ducts in the subcutaneous layer, even at the sites where the NIR had proved ineffective. Conclusion: Based on our results, we suggest that the procedure for identifying lymphatic vessels using the newly developed LW is a useful technique that can be utilized before performing a LVA for lymphedema. However, further clinical study is required to develop this device and technique, for wider clinical application in the future.

A dermoid cyst misdiagnosed as a lipoma due to atypical magnetic resonance images: a case report.

BACKGROUND: Dermoid cysts are well-known lesions that manifest as subcutaneous tumors around the lateral sides of the eyebrows in young patients. Computed tomography or magnetic resonance imaging (MRI) is often performed to confirm the diagnosis. On the other hand, a lipoma is usually a circular lesion, which is sometimes observed in the upper part of the face. The signals of both T1-weighted and T2-weighted images of MRI of a lipoma are, in general, relatively highly homogenous, and the signals decrease in fat-suppressed images. Therefore, differential diagnosis between a dermoid cyst and a lipoma is usually made with MRI, especially based on fat-suppressed images. Here, we present a case of misdiagnosis of a dermoid cyst as a lipoma because of atypical magnetic resonance images. CASE PRESENTATION: We report a case of a 24-year-old Japanese woman with a dermoid cyst around the lateral edge of the eyebrow. The cyst had been gradually increasing in size for the past 2 years. On MRI, it showed high internal signals on T1- and T2-weighted images. However, the signal intensity decreased homogeneously in the fat-suppressed T2-weighted images. The observed tumor had a yellowish appearance under the endoscope. On the basis of these findings, the lesion was considered a lipoma until it ruptured intraoperatively. The pathological diagnosis confirmed it to be a dermoid cyst. CONCLUSION: Some dermoid cysts contain lipid-rich liquid, and these may be misdiagnosed as lipomas by MRI. When a tumor is located at a common site for a dermoid cyst, the MRI images should be validated carefully if it appears like a lipoma, and the differential diagnosis should be considered carefully.

Lymphaticovenous shunt for the treatment of chylous reflux by subcutaneous vein grafts with valves between megalymphatics and the great saphenous vein: a case report.

Chylous reflux is a rare disorder in which chyle flows antidromically from its normal route to the extremities, thorax, abdominal cavity, or other parts of the body. We present a case of chylous reflux with megalymphatics in a 28-year-old boy who presented chylorrhea in the foot, leg, and external genitalia, lymphedema, and hemangioma in the affected limb. Lymphaticovenous shunts using subcutaneous vein grafts with valves were applied to the patient for treatment of repeated chylorrhea. After surgery, the patient has not complained of chylorrhea and been freed from conservative physiotherapy such as bandaging or application of compression stockings for lymphedema for two years. A subcutaneous vein graft with valves may be considered a useful method as a shunt between incompetent and dilated lymphatics and veins instead of a saphenous vein graft in the treatment of chylous reflux in lower extremities. We discuss these treatments based on the literature about chylous disorders.

Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis.

Several authors have reported the usefulness and benefits of lymphoscintigraphy. However, it is insufficient to indicate microvascular treatment based on lymphedema. Here, we present the relationships between lymphoscintigraphic types and indications for lymphatic microsurgery. Preoperative lymphoscintigraphy was performed in 142 limbs with secondary lymphedema of the lower extremity. The images obtained were classified into five types. Type I: Visible inguinal lymph nodes, lymphatics along the saphenous vein and/or collateral lymphatics. Type II: Dermal backflow in the thigh and stasis of an isotopic material in the lymphatics. Type III: Dermal backflow in the thigh and leg. Type IV: Dermal backflow in the leg. Type V: Radiolabeled colloid remaining in the foot. Lymphaticovenous anastomosis was performed in 35 limbs. The average number of anastomoses per limb was 3.3 in type II, 4.4 in type III, 3.6 in type IV, and 3 in type V. The highest number of anastomosis was performed in type III. In conclusion, type III is suggested to be the best indication for anastomosis compared with types IV and V.

Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation.

Background: Lymphedema includes primary lymphedema (P-LE) and secondary lymphedema (S-LE), which is a chronic progressive disease. The former group is further classified as congenital and acquired P-LE (AP-LE); its etiology is unclear, and only a few studies on its pathophysiology exist. We hypothesized that an autoimmune disease or self-inflammatory mechanism occurs in lymphatic vessels, leading to obstruction. Methods and Results: We enrolled 46 patients with lymphedema who underwent lymphaticovenous anastomosis (LVA) from January to October 2015. Collecting lymph ducts were obtained during LVA. We performed hematoxylin/eosin staining and immunostaining for LYVE-1, IL-1ß, IL-6, and TNF-α. There were no substantial histological differences between the two types of lymphedema, whereas some differences in expression of inflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, were observed. Only a few inflammatory cells could be seen around the vessels. Although no significant differences in expression of IL-1ß were found between AP-LE and S-LE, TNF-α was more highly expressed in the smooth muscle layer in AP-LE patients than in S-LE patients. There were no significant morphological differences in the collecting ducts of lymphatic vessels between S-LE and P-LE. Nevertheless, higher levels of TNF-α accumulation were found in the thick smooth muscle layer of P-LE patients than in that of S-LE patients. Conclusion: TNF-α-related inflammation in collecting ducts of lymphatic vessels is an important characteristic of the pathology of P-LE. TNF-α inhibitors might improve symptoms of AP-LE.

Low-density-lipoprotein apheresis-mediated endothelial activation therapy to severe-peripheral artery disease study: Rationale and study design.

A novel approach is required for standard therapy-resistant peripheral arterial disease (PAD). This is a single-center, single-arm, interventional study (LDL Apheresis-Mediated Endothelial Activation Therapy to Severe-Peripheral Artery Disease study), which aims to evaluate the efficacy and safety of lipoprotein apheresis (LA) with a dextran sulfate cellulose column in PAD with controlled serum cholesterol levels. The study participants have standard therapy-resistant PAD with controlled serum cholesterol levels. A total of 35 patients undergo 10 sessions of LA therapy. The ankle-brachial index and vascular quality of life questionnaire are assessed before and after the treatment period as primary outcomes. Registration of patients began in November 2015 and is planned to be concluded in October 2020.

Pathological changes in the lymphatic system of patients with secondary upper limb lymphoedema.

Secondary upper limb lymphoedema is usually caused by lymphatic system dysfunction. Diagnosis is primarily based on clinical features. However, there are no distinct diagnostic criteria for lymphoedema. Although conventional lymphoscintigraphy is a useful technique to diagnose the severity of lymphoedema, the resultant data are two-dimensional. In this study, we examined the pathology of lymphoedema using single photon emission computed tomography-computed tomography lymphoscintigraphy (SPECT-CT LSG), a new technique that provides 3-dimensional information on lymph flow. We observed lymph flow pathways in the subcutaneous and muscle layers of the upper limbs. A significant positive correlation was found between the dermal back flow (DBF) type and the visualization of lymph nodes around the clavicle (p = 0.000266), the type of lymph flow pathways and the visualization of lymph nodes around the clavicle (p = 0.00963), and the DBF type and the lymph flow pathway (p = 0.00766). As the severity of lymphoedema increased, the DBF appeared more distally in the upper limb and the flow into the lymph nodes around the clavicle decreased, whereas the lymph flow pathways in the muscle layer became dominant. These findings demonstrate the features of lymphoedema pathology and the functional anatomy and physiology of the lymphatic system without the need for cadaver dissection.

Real-Time Direct Evidence of the Superficial Lymphatic Drainage Effect of Intermittent Pneumatic Compression Treatment for Lower Limb Lymphedema.

BACKGROUND: Intermittent pneumatic compression (IPC) is a widely used lymph drainage therapy that can be performed at home. However, the effectiveness of IPC for lymph drainage remains unclear. The aim of this study is to investigate the real-time change in the lymph flow velocity during IPC and consider which mode and pressure are best for treating lower limb lymphedema. METHODS AND RESULTS: Eight lower left limbs of 8 healthy volunteers and 17 lower limbs of 15 secondary lymphedema patients were investigated. Indocyanine green lymphography was performed with the subject covered with a transparent six-chambered IPC garment. The IPC treatment was administered in several modes (sequential or nonsequential inflation mode, sequential or interrupted deflation mode, and under high or low pressure). Using a brightness intensity analysis software program, the real-time change in the fluorescence intensity during the treatment was recorded and graphed. The maximum inclination of the graph between 2 seconds in the inflation phase (SLOPE) and the mean SLOPE value of all subjects (average SLOPE) were calculated. The average SLOPEs of each mode of treatment were then compared. The average SLOPEs were also compared between patients with mild and moderate lymphedema. There were no significant differences among the SLOPEs in the healthy group. However, in the patient group, the average SLOPE was significantly higher in the sequential inflation mode as well as under high pressure than in the nonsequential inflation mode. On comparing the mild and moderate lymphedema groups, the average SLOPE tended to be higher in the mild group; however, the difference was not statistically significant. CONCLUSIONS: Sequential programs and high pressure resulted in a faster lymphatic flow than other modes. These results suggest that a greater treatment effect could be obtained by adjusting the mode of treatment and the pressure of IPC.