Naoki Murao

A New Uniform Protocol of Combined Corticosteroid Injections and Ointment Application Reduces Recurrence Rates After Surgical Keloid/Hypertrophic Scar Excision

BACKGROUND Published reports indicate that corticosteroid injections can prevent recurrence after keloid excision, but the side effects of repetitive intralesional steroid injections may preclude treatment maintenance. Additionally, few of these studies employed a standardized treatment protocol. OBJECTIVES To analyze the results of a new uniform treatment protocol combining corticosteroid injections and ointment application designed to reduce recurrence rates after excisional surgery in individuals with keloids or hypertrophic scars. METHODS As a standard procedure, the first corticosteroid injection took place after removal of the sutures and then once every 2 weeks after that until it had been done five times. In addition, all postsurgical wounds received self‐administered steroid ointment application twice daily for 6 months after suture removal. RESULTS Postoperative follow‐up in this series ranged from 24 to 57 months (median 32 months, mean 32.5 months). Recurrence occurred in three of the 21 keloid cases (14.3%) and one of the six hypertrophic scar cases (16.7%). CONCLUSION We evaluated a new standardized adjuvant corticosteroid therapy to prevent recurrence after surgical keloid or hypertrophic scar excision. Using this method, we achieved low recurrence rates.

Treg-enriched CD4+ T cells attenuate collagen synthesis in keloid fibroblasts

Keloid is an inflammatory and fibrotic disease with an unknown pathogenesis. Regulatory T cells (Tregs) of CD4+ lineage can suppress other effector CD4+ T cells and modulate the immune response. A relative decrease in the number of Tregs may be involved in the pathogenesis of inflammatory and fibrotic diseases. We therefore investigated the number of Tregs in keloids using immunohistochemistry and examined the interaction between Tregs and keloid fibroblasts (KFs) using a coculture system. It was found that the ratio of Tregs/CD4+ T cells was lower compared with that in other common inflammatory skin conditions. In addition, Treg‐enriched CD4+ T cells reduced collagen synthesis by KFs. Our findings suggest that a local imbalance of Tregs contributes to the development of keloids and that correction of this imbalance might represent a novel therapeutic approach to keloid fibrosis.

Combination of Tessier clefts 3 and 4: Case report of a rare anomaly with 12 years' follow-up

Tessier cleft types 3 and 4 are both rare craniofacial anomalies. Here we present the first case of a girl born with a combined anomaly of Tessier clefts 3 and 4 with severe bilateral cleft lip, a displaced premaxilla, and three-dimensional underdevelopment of the hard and soft tissues of the maxilla and zygoma. This type of rare facial cleft poses a major operative challenge. Over a period of years, presurgical alveolar molding with an active appliance was followed by seven operations. A satisfactory esthetic outcome was obtained. A multidisciplinary approach to treatment with a plastic surgeon in charge of the operations and an orthodontist in charge of the cleft deformity is essential.

Important points for primary cleft palate repair for speech derived from speech outcome after three different types of palatoplasty

OBJECTIVE This study was performed to investigate speech outcomes after three different types of palatoplasty for the same cleft type. The objective of this study was to investigate the surgical techniques that are essential for normal speech on the basis of each surgical characteristic. METHODS Thirty-eight consecutive nonsyndromic patients with unilateral complete cleft of the lip, alveolus, and palate were enrolled in this study. Speech outcomes, i.e., nasal emission, velopharyngeal insufficiency, and malarticulation after one-stage pushback (PB), one-stage modified Furlow (MF), or conventional two-stage MF palatoplasty, were evaluated at 4 (before intensive speech therapy) and 8 (after closure of oronasal fistula/unclosed hard palate) years of age. RESULTS Velopharyngeal insufficiency at 4 (and 8) years of age was present in 5.9% (0.0%), 0.0% (0.0%), and 10.0% (10.0%) of patients who underwent one-stage PB, one-stage MF, or two-stage MF palatoplasty, respectively. No significant differences in velopharyngeal function were found among these three groups at 4 and 8 years of age. Malarticulation at 4 years of age was found in 35.3%, 10.0%, and 63.6% of patients who underwent one-stage PB, one-stage MF, and two-stage MF palatoplasty, respectively. Malarticulation at 4 years of age was significantly related to the presence of a fistula/unclosed hard palate (P<0.01). One-stage MF palatoplasty that was not associated with postoperative oronasal fistula (ONF) showed significantly better results than two-stage MF (P<0.01). Although the incidences of malarticulation at 8 years of age were decreased in each group compared to at 4 years of age, the incidence was still high in patients treated with two-stage MF (45.5%). On the whole, there was a significant correlation between ONF/unclosed hard palate at 4 years of age and malarticulation at 8 years of age (P<0.05). CONCLUSION Appropriate muscle sling formation can compensate for a lack of retropositioning of the palate for adequate velopharyngeal closure. Early closure of the whole palate and the absence of a palatal fistula were confirmed to be essential for normal speech. To avoid fistula formation, multilayer repair of the whole palate may be critical.

Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical Refinement and Molecular Characteristics

Background: The pathophysiology of secondary lymphedema remains poorly understood. This study aimed to establish a consistent mouse hindlimb lymphedema model for further investigation of the mechanism and treatment of lymphedema. Methods: The authors developed a novel postsurgical lymphedema model in the mouse hindlimb by modifying previously described methods. Lymphedema in the hindlimb was created by removing both the inguinal and popliteal lymph nodes together with the surrounding fat pads, followed by silicone splint placement in the inguinal region. Using this modified mouse model, the authors analyzed lymphatic function, histologic changes, and the expression of lymphangiogenic factors including vascular endothelial growth factor C at various time points. Results: The splinted lymphedema model showed a significant increase of edema formation in the hindlimb compared with the sham surgery control animals. Indocyanine green lymphography revealed lymphatic drainage impairment shown by dermal backflow and rerouting of lymph flow in the lymphedema model. Histopathologic and immunohistochemical examinations showed a significant increase of skin thickness and abnormally dilated lymphatics in the lymphedema model. The expression of lymphangiogenic factors in lymphedematous tissues of the splinted lymphedema model was significantly increased compared with controls, depending on the degree of lymphedema. Conclusions: This splinted lymphedema model closely simulates the volume response, histopathology, and lymphography characteristics of human acquired lymphedema. Given these similarities to human lymphedema, this refinement of a mouse hindlimb model of acquired lymphedema represents a promising platform for the study of lymphatic vascular insufficiency and for the evaluation of new therapeutic modalities.

Prevention of Lymphedematous Change in the Mouse Hindlimb by Nonvascularized Lymph Node Transplantation.

AbstractLymphedema is a condition characterized by progressive swelling and adipose deposition that occurs commonly after lymphadenectomy. Recent clinical studies have suggested that the transfer of lymph nodes to the lymphedematous limb can improve lymphatic function. In this report, we investigate dynamic modulation of lymphatic flow and the microscopic changes of lymphatic regeneration using a lymphedema mouse model that was treated with nonvascularized lymph node transplantation. To evaluate the effect of lymph node transplantation in this model, paw volume was measured using a water displacement plethysmometer; an indocyanine green fluorescence-sensitive camera system was used. The improvement of edema was evident in the paw of the transplantation group. The abnormal fluorescence image pattern gradually improved and disappeared 4 weeks postoperatively in the transplantation group. Uptake in the transplanted lymph node was observed 4 weeks postoperatively. This finding suggested that the transplanted lymph node was engrafted. A collateral pathway was observed in the ventral area 1 week postoperatively. The collateral pathway may have contributed to the early improvement of edema. Our findings suggest that lymph node transplantation can restore lymphatic function. This result has important conceptual implications in the treatment of postsurgical lymphedema.

Sentinel node biopsy versus elective lymph node dissection in patients with cutaneous melanoma in a Japanese population.

BackgroundIn Japan, elective lymph node dissection (ELND) has been the standard treatment for patients with possible nodal melanoma. Sentinel node biopsy (SNB) has now replaced ELND, not only in Japan but also worldwide. The objective of this study was to compare the interim outcomes of SNB and ELND.MethodsA retrospective study was conducted among patients with clinically node-negative disease treated at our institute with either SNB (n = 30) or ELND (n = 72).ResultsThe background was similar in the two groups. Nodal metastases were found in 40.0% of patients in the SNB group, but in only 26.4% in the ELND group (P = 0.173). The median follow-up was 31.5 months for the SNB group and 82 months for the ELND group. The incidence of locoregional recurrence and distant metastasis in the SNB group was 10.0% and 16.7%, respectively, and for the ELND group the incidence was 5.6% and 31.9%, respectively. The 3-year disease-free survival rate was similar in the two groups (P = 0.280), and the 3-year disease-free survival rates for node-positive patients were also similar in the two groups (P = 0.90), as were the 3-year disease-free survival rates for node-negative patients (P = 0.193).ConclusionThis interim result in a Japanese melanoma population with clinically node-negative disease demonstrated that SNB identified more nodal micrometastases than ELND. This increase in accurate staging likely resulted from the reliable identification of the lymph node field by lymphoscintigraphy, as well as the more detailed pathologic examination of the nodes removed in SNB. It is quite reasonable to perform SNB instead of ELND in this population.

Review and proposal of regional surgical management for melanoma: revisiting of integumentectomy and incontinuity dissection in treatment of skin melanoma

BackgroundPast studies showed that integumentectomy and incontinuity could be effective procedures in the surgical management of melanoma patients. The present study reports on the historical background of these procedures. In addition, we analyze the ICG assisted integumentectomy and incontinuity techniques and algorithms that we had created when performing this procedure.MethodIn accordance with our algorithm, we performed ICG assisted integumentectomy/incontinuity procedures on 17 patients with stage III melanomas between 2008 and 2016. We also investigated the locoregional recurrence rate in a control group comprising 60 patients at stage III without using the algorithm.ResultsThe former group exhibited a tendency of locoregional recurrence rate suppression. Melanoma cells in the dissected intervening tissue were microscopically identified in 2 out of 17 cases.ConclusionsOur ICG assisted integumentectomy or incontinuity procedures could be effective in controlling locoregional recurrence rates in melanoma cases. Moreover, our method can be generally applied because the dissection is only performed within the lymphatic pathway region identified using indocyanine green.

Promising long-term outcomes of the reused skin-graft technique for chronic gluteal hidradenitis suppurativa

BACKGROUND The reused skin-graft technique can be used to treat chronic gluteal hidradenitis suppurativa, but long-term outcomes and the reliability of the technique have not been reported. METHODS In a retrospective review of 18 men with chronic gluteal hidradenitis suppurativa (age range, 18-68 years) treated with a reused skin graft between June 2004 and March 2012, we evaluated disease severity (Hurley classification system), skin-graft thickness, the need for an additional normal skin graft, histological findings and recurrence rate at the surgical site. RESULTS The mean duration of follow-up was 61.3 months (range, 17-113 months). Five cases were classified into severity group I, 12 cases into severity group II and one case into severity group III. The range of skin-graft thicknesses was 0.013-0.020 inches. An additional donor site was unnecessary in 10 cases (three cases in group I (60%) and seven cases in group II (58.3%)). Histological examination indicated that a buried epidermal cyst could cause chronic gluteal hidradenitis suppurativa recurrence, although none of the patients experienced recurrence at the surgical site during follow-up. CONCLUSION The reused skin-graft technique is reliable for chronic gluteal hidradenitis suppurativa resection, and it shows promising long-term outcomes.

Immune-mediated antitumor effect of a transplanted lymph node: Antitumor effect of a transplanted lymph node

Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non‐vascularized LN, defined as a tumor‐draining transplanted lymph node (TDTLN), could exert an immune‐mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16‐F10‐luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor‐draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T‐cells and B‐cells and fluorescence‐activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune‐mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non‐vascularized LN transplantation had an immune‐mediated antitumor effect.