Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The primary aim of this study was to determine the detailed anatomy of the lymphatics in the lower extremity using fresh human cadavers with indocyanine green fluorescence lymphography. The secondary aim was to apply the anatomical results to establish a new protocol for lymphography based on feasible allocations for tracer injection sites. METHODS: One hundred lower extremities from 53 fresh human cadavers were used for this study. The authors injected indocyanine green solution subcutaneously at 19 points around the foot along the borderline between the dorsum and planta according to anatomical landmarks. Immediately after the indocyanine green injections, gentle hand massage was applied at each injection site to facilitate indocyanine green uptake into the lymphatic vessels. Fluorescent images of the lymphatics were obtained using a near-infrared camera system. Imaging data of the lymphatics were analyzed to find correlations between the injection sites and the identified lymphatic vessels. RESULTS: The lymphatic system in the lower extremity was divided into four distinct lymphatic groups: anteromedial, anterolateral, posterolateral, and posteromedial. The lymphatic vessels in all except the posterolateral group connected to the inguinal nodes, and those in the posterolateral group connected to the popliteal nodes. The authors successfully elucidated correlations between the injection sites in the foot and each lymphatic group. CONCLUSION: The new classification of the four lymphatic groups in the lower extremity and identification of their origins in the foot enabled the authors to propose a new protocol for lymphography that includes four injection sites in specific circumflex locations.

DOI： 10.1097/PRS.0000000000005982

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Identification of the lymphatic system in cadavers is painstaking because lymphatic vessels have very thin walls and are transparent. Selection of appropriate contrast agents is a key factor for successfully visualizing the lymphatics. In this study, the authors introduce a new imaging technique of lymphatic mapping in the whole bodies of fresh cadavers. METHODS: Ten fresh human cadavers were used for this study. The authors injected 0.1 ml of indocyanine green fluorescence solution subcutaneously at multiple spots along the watershed lines between lymphatic territories and hand and foot regions. After the body was scanned by the near-infrared camera system, fluorescent tissues were harvested and histologic examination was performed under the microscope equipped with the infrared camera system to confirm that they were the lymphatics. RESULTS: Subcutaneously injected indocyanine green was immediately transported into the lymphatic vessels after gentle massage on the injection points. Sweeping massage along the lymphatic vessels facilitated indocyanine green transport inside the lymphatic vessel to move toward the lymph nodes. The lymphatic system was visualized well in the whole body. Histologic examinations confirmed that indocyanine green was detected in the lymphatic lumens specifically, even when located far from the injected points. CONCLUSIONS: The lymphatic system could be visualized in whole-body fresh cadavers, as in living bodies, using indocyanine green fluorescence lymphography. Compatibility of indocyanine green lymphography would facilitate the use of cadaveric specimens for macroscopic and microscopic analyses.

DOI： 10.1097/PRS.0000000000004315

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：THIEME MEDICAL PUBL INC  

Background The purpose of this study was to evaluate the lymph function of the lower extremities and to identify early symptoms of lymph dysfunction in secondary lymphedema by observing lymph flow with indocyanine green (ICG) fluorescence lymphography (LG).
Methods We retrospectively evaluated the lymph flow of 108 limbs in 54 female patients with leg lymphedema secondary to pelvic lymphadenectomy for gynecological carcinoma and 14 limbs in 7 female controls without a history of pelvic lymphadenectomy or radiotherapy. ICG was injected into four points at the distal part of the lower extremity. Lymph flow was evaluated by measuring the proximal point where the ICG could be observed 5 minutes after rest and 15 minutes after a walking exercise.
Results In the controls, lymph flow was stable at rest and was well enhanced by exercise. In patients with early-stage lymphedema, lymph flow was already enhanced at rest (p = 0.005) and was further enhanced by exercise. In advanced-stage lymphedema, lymph flow was not enhanced, even by exercise (p = 0.001).
Conclusion ICG-LGcould evaluate lymph flow and functions of lymph systems and detect accelerated lymph flow in early-stage secondary lymphedema. Detecting accelerated lymph flow may facilitate early detection and treatment of secondary lymphedema.

DOI： 10.1055/s-0037-1603740

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Language：Japanese   Publisher：(一社)日本マイクロサージャリー学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)日本関節病学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/prs.0000000000007014

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Language：English   Publisher：(一社)日本マイクロサージャリー学会  

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The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.

DOI： 10.1016/j.yexcr.2019.111556

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DOI： 10.1002/micr.30467

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The hemodynamics of blood flowing from the anterior serratus to the ribs has yet to be analyzed in detail in serratus anterior/rib composite flaps. The authors focused on new blood circulation, whereby the slip arteries branched from the serratus anterior branch, off the thoracodorsal artery and the intercostal arteries, directly through the interconnecting vessels (axial route). The authors analyzed in detail the hemodynamics of serratus anterior/rib composite flaps and developed a new method for flap elevation. METHODS: The axial route was identified and analyzed by performing macroscopic autopsies of formalin perfusion-fixed cadavers involving three-dimensional computed tomographic angiography and vascular corrosion casting. Flap elevation was performed with new blood circulation, which included the axial route, and blood flow was evaluated using indocyanine green fluorescence angiography. RESULTS: The interconnecting vessels penetrated the intercostal muscles at a mean distance of 4.5 cm from the anterior margin of the attachment sites of the serratus anterior muscle to the ribs and at a mean distance of 7.4 cm from the costochondral junction. The interconnecting vessels had a mean diameter of 0.5 mm. Vascular corrosion casting helped identify multiple capillaries that were distributed from the intercostal arteries to the periosteum of the ribs. In addition, intraoperative indocyanine green fluorescence angiography confirmed blood flow from the slip arteries to the intercostal arteries. CONCLUSION: Good blood flow in harvested graft tissue can be achieved by including the axial route with the periosteal blood circulation at the rib attachment sites of the serratus anterior in a serratus anterior/rib composite flap.

DOI： 10.1097/PRS.0000000000005087

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Hyaluronan (HA) is an extracellular matrix (ECM) component of articular cartilage and has been used to treat patients with osteoarthritis (OA). A disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs) play an important role in cartilage degradation in OA. We have previously reported that ADAMTS4 and ADAMTS9 were induced by cytokine stimulation. However, the effect of HA on the cytokine-inducible ADAMTS9 has never been investigated. Moreover, it is unclear whether HA protects cartilage by suppressing aggrecan degradation. Here, we examined the effects of HA on ADAMTS expression in vitro and on cartilage degradation in vivo. ADAMTS9 expression was higher than that of the other aggrecanases (ADAMTS4 and 5) in human chondrocytes, chondrocytic cells, and rat cartilage. ADAMTS4 and 9 mRNA levels were upregulated in cytokine-stimulated chondrocytes and chondrocytic cells. Pre-incubation with HA significantly inhibited ADAMTS9 mRNA expression in cytokine-stimulated cells. In a rat OA model, Adamts5 and 9 mRNA levels were transiently increased after surgery; intra-articular HA injections attenuated the induction of Adamts5 and 9 mRNA. HA also blocked aggrecan cleavage by aggrecanase in OA rats in a molecular size-dependent manner. These results demonstrate that HA attenuates induced aggrecanases expression in OA and thereby protects articular cartilage degradation by this enzyme. Our findings provide insight into the molecular basis for the beneficial effects of HA in OA. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:3247-3255, 2018.

DOI： 10.1002/jor.24126

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Language：Japanese   Publisher：(一社)日本マイクロサージャリー学会  

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Language：Japanese   Publisher：(一社)日本マイクロサージャリー学会  

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Language：Japanese   Publisher：(一社)日本マイクロサージャリー学会  

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Language：English  

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Language：English   Publishing type：Research paper (scientific journal)  

Despite various options for the reconstruction of soft tissue defects in the distal forearm, perforator-based propeller flap is rarely used. Here, we presented 2 cases of distal forearm injuries that were repaired using the recurrent branch of anterior interosseous artery perforator-based propeller flap. Patients in these cases were 57 and 67 years of age. Wounds resulting from farming machine injury and pyogenic extensor tenosynovitis following cat bite wounds were localized to the distal forearm and dorsum of the hand. Defect dimensions were 5 cm × 10 cm and 5 cm × 8 cm. The 12 cm × 7 cm and 21 cm × 4 cm sized recurrent branch of anterior interosseous artery perforator-based propeller flap was designed adjacent to the wounds. In the latter case, the absence of the posterior interosseous artery in the distal forearm was observed. One perforator from the recurrent branch of the anterior interosseous artery emerged through the septum between the extensor digiti minimi and extensor carpi ulnaris 7.5 cm and 6.0 cm proximal to the ulnar head in cases 1 and 2, respectively. Perforators were identified using multidetector computed tomographic angiography and handheld Doppler. Extending to two-thirds or almost the full length of the forearm, the flaps were raised and rotated by 90° and 120° to cover the defect. The donor sites were closed using free skin graft. Both flaps survived. Except for minor wound dehiscence and hemarthrosis, no other postoperative complications occurred. Patients returned to work or daily activities at 3- and 4-month follow-up after surgery.

DOI： 10.1002/micr.30388

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

As a new trial, we used interstitial computed tomography-lymphography (CT-LG) in 10 patients with lower extremity lymphedema (n= 20 limbs) at stage 0, 1, 2, or 3 under the International Society of Lymphology (ISL) classification. In all cases, CT-LG, lymphoscintigraphy, and indocyanine green fluorescence-lymphography (ICG-LG) were performed. In the examination of the ascending level of depicted lymphatic vessels, we measured the diameters of lymphatic vessels detected with CT-LG and conducted an image analysis of dermal backflow of lymph (DB). CT-LG had better resolution than lymphoscintigraphy and enabled the clear visualization of lymphatic vessels with a minimum lumen size of 0.7 mm. CT-LG also showed the three-dimensional architecture of the DB, which originated from deep lymphatic collectors via branched small lymphatic vessels. Our findings are quite valuable not only for detailed examinations of lymphedematous sites and for the lymphedema surgery, but also for investigations of the pathogenesis of lymphedema which has not yet been established. We observed that lymphoscintigraphy could show the lymphatic vessels up to the thigh level in all cases, whereas CT-LG enabled the vessels' visualization up to the leg level at maximum. In conclusion, CT-LG provided adequate and detailed three-dimensional imaging of the lymphatic system in lymphedema patients.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：THIEME MEDICAL PUBL INC  

Background The treatment of trauma to the lower extremities often carries a high risk of complications. To the best of our knowledge, no study has been published regarding the treatment of open lower-limb fractures using laser-assisted indocyanine green angiography (LA-ICG). Here we retrospectively evaluated LA-ICG based therapeutic interventions and reported the use of LA-ICG and its results in this application.
Patients and Methods Between January 2011 and December 2015, a total of 23 cases with Gustilo grade IIIB open lower-limb fractures were investigated. LA-ICG was used to demonstrate the presence of necrotic tissue and determine the range of debridement. We compared 13 patients treated using LA-ICG from 2013 to 2015 with 10 patients treated without LA-ICG from 2010 to 2013. We reviewed tissue necrosis and other outcomes of these patients.
Results The tissue necrosis rate in the LA-ICG used group was significantly lower than that in the LA-ICG free group. There were also significant differences in the average number of instances of tissue necrosis per patient, debridements, and deep-site infections. There was no flap loss.
Conclusion By using LA-ICG, not only plastic surgeons but also clinicians in all associated departments including orthopedics can perform early reliable debridement and share in trauma treatment planning. We will continue to accumulate similar cases and hope to further improve LA-ICG techniques.

DOI： 10.1055/s-0036-1593807

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

A variety of lymphatic imaging techniques have been developed, but no technique can provide real-time imaging except for indocyanine green fluorescent lymphography (ICG-LG). The real-time images of ICG-LG make lymphaticovenous anastomosis (LVA) easy to perform. In this chapter, history and methods of ICG-LG for LVA are described in detail.

DOI： 10.1007/978-4-431-55528-5_40

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Most blood vessels contain elastin that provides the vessels with the resilience and flexibility necessary to control hemodynamics. Pathophysiological hemodynamic changes affect the remodeling of elastic components, but little is known about their structural properties. The present study was designed to elucidate, in detail, the three-dimensional (3D) architecture of delicate elastic fibers in small vessels, and to reveal their architectural pattern in a rat model. The fine vascular elastic components were observed by a newly developed scanning electron microscopy technique using a formic acid digestion with vascular casts. This method successfully visualized the 3D architecture of elastic fibers in small blood vessels, even arterioles and venules. The subendothelial elastic fibers in such small vessels assemble into a sheet of meshwork running longitudinally, while larger vessels have a higher density of mesh and thicker mesh fibers. The quantitative analysis revealed that arterioles had a wider range of mesh density than venules
the ratio of density to vessel size was higher than that in venules. The new method was useful for evaluating the subendothelial elastic fibers of small vessels and for demonstrating differences in the architecture of different types of vessels. © Microscopy Society of America 2013.

DOI： 10.1017/S1431927612014341

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Language：Japanese   Publisher：日本結合組織学会・マトリックス研究会  

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Language：Japanese   Publisher：(一社)日本解剖学会  

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Language：Japanese   Publisher：(一社)日本解剖学会  

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Language：Japanese   Publisher：(一社)日本解剖学会  

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Language：English   Publisher：生命科学系学会合同年次大会運営事務局  

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Language：Japanese   Publisher：日本結合組織学会  

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Language：Japanese   Publisher：日本結合組織学会  

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J-GLOBAL

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Symposium, workshop panel (nominated)  

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Country：Japan

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Country：Japan

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Country：Japan

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Country：Japan

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