Ran Ito

Overview of lymph node transfer for lymphedema treatment.

SUMMARY Recent articles report that surgery can effectively treat secondary lymphedema. Lymphovenous anastomosis with supermicrosurgery technique has become popular for surgical intervention for lymphedema and has an advantage of minimal morbidity. Lymphovenous anastomosis is effective for treating early-stage lymphedema before fibrosis occurs but has limited outcomes in advanced lymphedema. Lymph node transfer is an emerging physiologic surgical treatment for lymphedema that shows promise. The mechanisms of lymph node transfer have been discordant between publications. However, initial reports encourage surgeons to use lymph node transfer to treat lymphedema patients. The authors review the literature on lymph node transfer and discuss its possible mechanisms and its role in lymphedema treatment.

Treating a collagen scaffold with a low concentration of nicotine promoted angiogenesis and wound healing.

BACKGROUND Nicotine, one of the major pharmacologically active agents of cigarette smoke, has various effects on cell proliferation, and it has recently been reported to have angiogenic effects. In our previous study, we showed that the topical administration of nicotine at a low concentration accelerated wound healing. This study aimed to evaluate the efficacy of nicotine and synergistic effects of combination treatment with nicotine and basic fibroblast growth factor (bFGF) in a murine excisional wound model treated with artificial dermis. METHODS Full-thickness defects (8 mm in diameter) were created on the backs of mice, and artificial dermis was sutured to the defects. Phosphate-buffered saline (10 μL), nicotine (10(-3), 10(-4), or 10(-5) M), bFGF (0.5 μg), and both bFGF and 10(-4) M nicotine were topically administered to the artificial dermal tissue for 7 d. The mice were killed on day 14, and the wound area, neoepithelium length, and area of newly formed capillaries in the artificial dermis were evaluated. RESULTS The wound areas treated with 10(-4) M nicotine, bFGF, or bFGF plus 10(-4) M nicotine were significantly smaller than those in the control group. In these three groups, the neoepithelium in the bFGF plus 10(-4) M nicotine group was significantly longer than that in the other groups. There was no significant difference between the neoepithelium lengths of the control and 10(-5) M nicotine groups. The 10(-3) M nicotine group displayed the least re-epithelization among the groups. CONCLUSIONS In this study, 10(-4) M nicotine induced angiogenesis in, and accelerated the healing of, wounds treated with artificial dermis. bFGF and nicotine had synergistic effects, and the combined use of nicotine and bFGF is an effective wound healing method.

Adipogenesis using human adipose tissue-derived stromal cells combined with a collagen/gelatin sponge sustaining release of basic fibroblast growth factor

We have developed a collagen/gelatin sponge (CGS) that can provide a sustained release of basic fibroblast growth factor (bFGF). In our previous study, it was shown that CGS impregnated with the appropriate dosage of bFGF accelerates dermis‐like tissue formation two or three times earlier than an existing collagen sponge. In this study, adipogenesis was evaluated using CGSs disseminated with adipose tissue‐derived stem cells (ASCs). Human ASCs were primarily isolated from human adipose tissue that was obtained during breast cancer surgery with informed consent at Kyoto University Hospital. ASCs were isolated from collagenase digests of adipose tissue. ASCs were labelled with PKH26. CGSs (8 mm diameter × 3 mm thickness) were impregnated with bFGF (0.1, 1, 7, 14 µg/cm2) or normal saline solution. Then the labelled cells were disseminated (passage 3) on CGSs at a seeding density of 1 × 105 cells/cm2 and implanted into the back subcutis of nude mice. Six weeks after implantation, adipogenesis at the administered site was evaluated. Immunohistological staining with von Willebrand factor (vWf) was performed to evaluate newly formed capillaries. Newly formed adipose tissue was observed macroscopically and histologically in all groups. The weight and area of regenerated adipose tissue were largest in the 1 µg/cm2 bFGF group. Under a fluorescent microscope, newly formed adipose tissue in the bFGF‐administered group was PKH‐positive. These findings show that ASCs differentiated and formed adipose tissue. In this study, we showed that our CGSs impregnated with bFGF could be used as scaffolds with ASCs for adipogenesis. Copyright

Successful treatment of early-stage lower extremity lymphedema with side-to-end lymphovenous anastomosis with indocyanine green lymphography assisted

This study was to investigate intraoperative assessment of side‐to‐end lymphovenous anastomosis (LVA) with indocyanine green (ICG) and the correlation between its patency and surgical outcome.

Proposed pathway and mechanism of vascularized lymph node flaps

OBJECTIVE To investigate the pump mechanism and pathway of lymph transit in vascularized lymph node flaps. BACKGROUND Microsurgical treatment of lymphedema with vascularized lymph node transfer can improve signs and symptoms of disease, but the pathways and mechanisms of these flaps warrant further exploration. METHODS (Animal model) 72 flaps were raised in 18 rats: 36 groin flaps contained lymph nodes (LN), 36 deep inferior epigastric artery perforator flaps did not (non-LN). Indocyanine green (ICG) was added into normal saline (NS), 1%, 3%, 5%, 7% and 10% albumin. Three rats were assigned to each group. LN and non-LN flaps were submerged in solution and surveyed for venous fluorescence. In the 7% albumin and NS groups, volumetric change of solution was measured. (Human model) A similar experiment was performed in humans using five submental LN flaps. RESULTS (Animal model) Fluorescence was detected in the venous pedicle of LN flaps submerged in 5%, 7% and 10% albumin, and half of flaps submerged in 3% albumin. Fluorescence was not detected in LN node flaps submerged in ICG-containing NS or 1% albumin solution. Fluorescence was not detected in non-LN flaps. There was greater volume reduction with LN flaps than non-LN flaps (p<0.001). (Human model) Fluorescence was detected in the venous pedicle of all flaps immersed in lymph. CONCLUSIONS ICG fluorescence was detected in the venous pedicle of rat and human LN flaps submerged in lymph or albumin when the concentration was greater than 3%. Based on these results, a pathway for lymphatic uptake is presented.

Lymphatic Territories (Lymphosomes) in Swine: An Animal Model for Future Lymphatic Research.

Background: The swine is a common preclinical large-animal model for medical research because of the resemblance of its tissue structures to those of humans. However, the lymphatic system in swine is poorly understood. The authors investigated the lymphatic system and defined territories (lymphosomes) in swine using the microinjection technique. Methods: Six swine (two male and four female 17.5- to 50-kg Sus domesticus) were used. Real-time indocyanine green fluorescence lymphography was performed in four live swine. After the animals were killed, the authors injected a radiocontrast mixture consisting of barium sulfate and hydrogen peroxide with red acrylic dye directly into lymphatic vessels in six swine carcasses. Courses of the lymphatic vessel were analyzed radiographically. The lymphatic vessels were dissected meticulously and chased until they connected to the first-tier (sentinel) lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. Results: The authors successfully mapped the superficial lymphatic vessels and their corresponding lymph nodes. Indocyanine green fluorescence lymphography and subsequent radiography revealed that the swine lymphatic system contained seven lymphosomes: parotid, mandibular, dorsal cervical, ventral cervical, subiliac, inguinal, and popliteal territories. Of note, no lymph nodes existed in the superficial axillary region. Conclusions: The swine could be a useful large-animal model for lymphatic research because of the anatomical consistency of the lymphosomes among animals and the sizable lymphatic vessels. However, swine lack the superficial axillary lymph node found in humans, suggesting that swine may not be a good model for breast cancer–related lymphedema.

Challenging a traditional paradigm: 12-year experience with autologous free flap breast reconstruction for inflammatory breast cancer.

Background: Inflammatory breast cancer is a rare but aggressive breast cancer with an overall poor prognosis. Traditionally, reconstruction has not been offered, because of poor long-term survival, the need for multimodality treatment, and complex treatment sequencing. The authors examined the safety and feasibility of free flap breast reconstruction for inflammatory breast cancer. Methods: A retrospective analysis of all patients who underwent reconstruction for inflammatory breast cancer from January of 2000 to December of 2012 was conducted. Results: Of 830 inflammatory breast cancer patients, 59 (7.1 percent; median age, 48 years; range, 27 to 65 years) underwent free flap reconstruction. All patients received chemotherapy and radiation therapy. Most patients (n = 52) underwent delayed reconstruction. Five patients with a history of prior partial mastectomy and irradiation developed inflammatory breast cancer and underwent immediate reconstruction following completion mastectomy. Two others underwent immediate chest wall and breast reconstruction following resection. Thirteen patients underwent bilateral reconstruction, and seven required a bipedicled abdominal flap for the unilateral mastectomy defect. Thirty-seven patients (62.7 percent) required revision of the reconstructed breast, and 29 (49.2 percent) had a contralateral balancing procedure to optimize symmetry. Complications occurred in 21 patients (35.6 percent), with one total flap loss (1.7 percent). The median length of follow-up was 43.9 months; 49 patients (83.1 percent) were alive without evidence of recurrent disease. Conclusions: Autologous free flap breast reconstruction can be performed safely in inflammatory breast cancer patients, with acceptable complication rates and without an increased risk for flap loss. Inflammatory breast cancer should not preclude free flap breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A Comparison of Conventional Collagen Sponge and Collagen-Gelatin Sponge in Wound Healing

The objective of this study was to compare the effectiveness of the collagen-gelatin sponge (CGS) with that of the collagen sponge (CS) in dermis-like tissue regeneration. CGS, which achieves the sustained release of basic fibroblast growth factor (bFGF), is a promising material in wound healing. In the present study, we evaluated and compared CGSs and conventional CSs. We prepared 8 mm full-thickness skin defects on the backs of rats. Either CGSs or CSs were impregnated with normal saline solution (NSS) or 7 μg/cm2 of bFGF solution and implanted into the defects. At 1 and 2 weeks after implantation, tissue specimens were obtained from the rats of each group (n = 3, total n = 24). The wound area, neoepithelial length, dermis-like tissue area, and the number and area of capillaries were evaluated at 1 and 2 weeks after implantation. There were no significant differences in the CGS without bFGF and CS groups. Significant improvements were observed in the neoepithelial length, the dermis-like tissue area, and the number of newly formed capillaries in the group of rats that received CGSs impregnated with bFGF. The effects on epithelialization, granulation, and vascularization of wound healing demonstrated that, as a scaffold, CGSs are equal or superior to conventional CSs.

Simultaneous Bilateral Submental Lymph Node Flaps for Lower Limb Lymphedema Post Leg Charles Procedure.

Summary: We summarize the case of a 59-year-old woman with left lower limb lymphedema for 4 years post hysterectomy, pelvic lymph node dissection, radiation therapy, and chemotherapy for endometrial cancer. She underwent the Charles procedure on her left leg 2 years before being referred to our hospital and developed several cellulitis episodes and progressive lymphedema affecting her left toes and thigh. Bilateral vascularized submental lymph node flaps were transferred to her left ankle and thigh, respectively. After a 5-month follow-up, the leg became softer and lighter without relapsing cellulites, and the circumferential reduction rates at 15 cm above knee, 15 cm below knee, and 10 cm above ankle were 23.3%, 50%, and 22.2%, respectively. The patient was satisfied with the functional recovery and discontinued use of compression garment postoperatively.

The versatility of profunda femoral artery perforator flap for oncological reconstruction after cancer resection—Clinical cases and review of literature

The profunda feomris artery perforator (PAP) flap was recently revisited and gains popularity as an alternative method of autologous breast reconstruction. The purpose of this article is to demonstrate that PAP flap can be used reliably for reconstruction of various soft tissue defects.