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Background: The timing of intervention to treat lymphedema differs among facilities. Understanding differences in the prevalence and severity of lymphedema following different surgical procedures for lymphadenectomy could promote early intervention to treat lymphedema. There is currently little evidence to support the notion that inguino-pelvic lymphadenectomy is associated with greater morbidity than inguinal lymphadenectomy, although it is believed that the difference in the extent of surgery results in a difference in the severity of lymphedema. In this study, we compared volume percentage change between inguinal lymphadenectomy and inguino-pelvic lymphadenectomy in patients with skin cancer of the lower extremity., Patients and Methods: A total of 29 patients with skin cancer of a lower extremity who underwent lymphadenectomy were classified into an inguinal lymphadenectomy group and an inguino-pelvic lymphadenectomy group. The increase in the volume of the affected side compared with that of the unaffected side in the whole lower extremity, thigh, and lower leg was calculated on volume-rendered computed tomography images., Results: The mean volume percentage increase in the inguinal lymphadenectomy group and the inguino-pelvic lymphadenectomy group was, respectively, 6.72% and 11.18% in the whole lower extremity and 7.30% and 2.55% in the lower leg, showing no statistically significant differences. In contrast, the mean volume percentage increase in the respective groups was 7.03% and 19.78% in the thigh, showing a statistically significant difference (p = 0.0275 < 0.05)., Conclusions: The findings of this study indicate that the leg volume of the whole lower extremity may not have worse outcomes in inguino-pelvic lymphadenectomy compared with inguinal lymphadenectomy., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Recent reports have indicated that vascularized lymph node transfer (VLNT) may improve the impaired immunity in lymphedema but there has been no report concerning anti-cancer immunity. In the early tumor immune response, dendritic cells (DCs) participate in tumor recognition and antigen presentation in local lymphatics. Here, we investigated the impact of VLNT on DC dynamics against cancer in mouse models., Methods: Forty-seven 8-week-old C57BL/6 N male mice were divided into three surgical groups: a VLNT model in which a vascularized inguinal lymph node (LN) flap was transferred into the ipsilateral fossa after a popliteal LN was removed; a LN dissection (LND) model in which the popliteal LN was dissected; and a control model in which a skin incision was made at the popliteal fossa and an ipsilateral inguinal LN was removed. Postoperative lymphatic flows were observed by indocyanine green lymphography and B16-F10-luc2 mouse melanoma were implanted into the ipsilateral footpad. The proportion of DCs in the transplanted nodes was measured by CD11c immunohistochemistry using digital imaging analysis 4 days after cancer implantation. Metastases to the lungs and LNs were quantitatively evaluated by luciferase assay 4 weeks after cancer implantation., Results: After VLNT, lymphatic reconnection was observed in 59.2% of mice. The proportion of DCs was significantly higher in the VLNT group with lymphatic reconnection (8.6% ± 1.0%) than in the naïve LN (4.3% ± 0.4%) (p < .001). The tumor burden of lung metastases was significantly less in the VLNT group with lymphatic reconnection compared with the LND group (p = .049)., Conclusions: Metastasis decreased in mice with reconnected lymphatics after VLNT. A possible explanation was that lymphatic restoration may have contributed to the tumor immune response by allowing DC migration to LNs., (© 2022 Wiley Periodicals LLC.)

Background Lymphedema is an intractable disease with no curative treatment available. Conservative treatment is the mainstay, and new drug treatment options are strongly needed. The purpose of this study was to investigate the effect of roxadustat, a prolyl-4-hydroxylase inhibitor, on lymphangiogenesis and its therapeutic effect on lymphedema in a radiation-free mouse hindlimb lymphedema model. : Male C57BL/6N mice (8-10 weeks old) were used for the lymphedema model. Mice were randomized to an experimental group receiving roxadustat or a control group. The circumferential ratio of the hindlimbs was evaluated, and lymphatic flow of the hindlimbs was compared by fluorescent lymphography up to 28 days postoperatively. The roxadustat group showed an early improvement in hindlimb circumference and stasis of lymphatic flow. The number and area of lymphatic vessels on postoperative day 7 were significantly larger and smaller, respectively, in the roxadustat group compared with the control group. Skin thickness and macrophage infiltration on postoperative day 7 were significantly reduced in the roxadustat group compared with the control group. The relative mRNA expression of hypoxia-inducible factor-1α ( Methods and Results : Male C57BL/6N mice (8-10 weeks old) were used for the lymphedema model. Mice were randomized to an experimental group receiving roxadustat or a control group. The circumferential ratio of the hindlimbs was evaluated, and lymphatic flow of the hindlimbs was compared by fluorescent lymphography up to 28 days postoperatively. The roxadustat group showed an early improvement in hindlimb circumference and stasis of lymphatic flow. The number and area of lymphatic vessels on postoperative day 7 were significantly larger and smaller, respectively, in the roxadustat group compared with the control group. Skin thickness and macrophage infiltration on postoperative day 7 were significantly reduced in the roxadustat group compared with the control group. The relative mRNA expression of hypoxia-inducible factor-1α ( Hif-1α ), vascular endothelial growth factor receptor-3 ( VEGFR-3 ), vascular endothelial growth factor-C ( VEGF-C Roxadustat demonstrated a therapeutic effect in a murine model of hindlimb lymphedema through promotion of lymphangiogenesis through the activation of HIF-1α, VEGF-C, VEGFR-3, and Prox1, suggesting the potential of roxadustat as a therapeutic option in lymphedema.Prox1 ) on postoperative day 4 was significantly higher in the roxadustat group compared with the control group. Conclusions : Roxadustat demonstrated a therapeutic effect in a murine model of hindlimb lymphedema through promotion of lymphangiogenesis through the activation of HIF-1α, VEGF-C, VEGFR-3, and Prox1, suggesting the potential of roxadustat as a therapeutic option in lymphedema.

Purpose: Severe lymphedema is difficult to treat because of the associated extensive scar formation. Therefore, preventing scar formation might alleviate the severity of lymphedema following lymphadenectomy. In this study, we evaluated the usefulness of flap transfer, performed immediately after lymphadenectomy, for preventing scar formation., Methods: Twenty-three patients with subcutaneous malignancy in a lower extremity, who underwent inguino-pelvic lymphadenectomy, were divided into groups based on whether flap transfer was performed. The severity of lymphedema was categorized according to the ratio of the circumference of the affected extremity to that of the unaffected extremity, as mild (< 20% increase in volume), moderate (20-40%), or severe (> 40%)., Results: In the 18 patients who underwent lymphadenectomy without flap transfer, lymphedema was classified as mild in 7, moderate in 7, and severe in 4. In the five patients who underwent lymphadenectomy with flap transfer, lymphedema was classified as mild in 4 and moderate in 1. This difference between the groups did not reach significance., Conclusions: The findings of this study suggest that flap transfer may help prevent scar formation and contribute to the restoration of lymph flow after lymphadenectomy., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Vascularized lymph node transfer is becoming more common in the treatment of lymphedema, but suitable small animal models for research are lacking. Here, we evaluated the feasibility of pedicled vascularized inguinal lymph node transfer in mice., Methods: Twenty-five mice were used in the study. An inguinal lymph node-bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node. Indocyanine green (ICG) angiography was used to confirm vascularity of the flap. ICG lymphography was performed to evaluate lymphatic flow at 3 and 4 weeks postoperatively. Patent blue dye was injected into the ipsilateral hind paw to observe staining of the transferred lymph node at 4 weeks postoperatively. All transferred lymph nodes were then harvested and histologically evaluated by hematoxylin and eosin staining., Results: In 16 of the 25 mice, ICG lymphography showed reconnection between the transferred lymph node and the afferent lymphatic vessels, as confirmed by patent blue staining. Histologically, these transferred lymph nodes with afferent lymphatic reconnection significantly regressed in size (0.37 ± 0.24 mm 2 ) and showed clear follicle formation, whereas those without afferent lymphatic reconnection showed less size regression (1.31 ± 1.17 mm 2 ); the cell population was too dense to allow identification of follicles., Conclusions: We established a mouse model of vascularized lymph node transfer with predictable afferent lymphatic reconnection. Both the vascularization and reconnection might be necessary for functional regeneration of the transferred lymph node., (© 2018 Wiley Periodicals, Inc.)