Recurrent cellulitis and bacteremia in a patient with Noonan syndrome: A case report.

A 28-year old Japanese man with Noonan syndrome (NS) presented to our emergency department with painful erythema of the trunk and lower extremities since the previous day. He had been diagnosed with protein-losing enteropathy (PLE) with intestinal lymphangiectasia at age 25 years, and undergone lymphaticovenular anastomosis (LVA) twice. Three episodes of cellulitis of both lower extremities had occurred in the past 2 years. Extensive cellulitis with sepsis was diagnosed and piperacillin/tazobactam was started, which was de-escalated to ceftriaxone. He was discharged after 13 days of antibiotic therapy. After discharge, low-dose trimethoprim-sulfamethoxazole (SMZ-TMP) was started as the primary prophylaxis, but three episodes of cellulitis occurred in the next year and were treated with other antibiotics. NS, an autosomal dominant disease known as a RASopathy, is caused by germline mutations in RAS-MAPK pathway genes. Lymphedema resulting from lymphatic abnormalities is a concomitant manifestation in 20 % of patients with NS, and can be a risk factor for cellulitis. Hypoalbuminemia and hypoglobulinemia associated with PLE facilitate infections such as cellulitis. As a treatment for lymphedema in the extremities, LVA has shown objective and subjective improvements in most patients, and some studies have also reported its efficacy for lymphedema in patients with NS. Targeted molecular therapy with mitogen-activated protein kinase enzyme (MEK) inhibitor is used in treatment of cancers with activation of the RAS/MAPK pathway. MEK inhibitors have recently been tried in patients with RASopathies and severe lymphatic disorders, and can lead to rapid resolution of symptoms.

[A Case of Reconstruction of the Osteoradionecrosis of the Jaw Using the Patient-Specific Custom-Made Cutting Guide and Mandibular Reconstruction Plate].

Multidisciplinary treatment, combining ablative surgery and reconstruction, radiotherapy, and chemotherapy, is used to treat advanced oral cancers. In this study, we report a case of extensive osteoradionecrosis of the mandible following multidisciplinary treatment for tongue cancer, in which a computer-assisted, patient-specific custom-made cutting guide and reconstruction plate(TruMatch® )were used to improve the patient's facial morphology and oral-maxillofacial functioning. A 70-year-old man received multidisciplinary treatment for squamous cell carcinoma of the left side of the tongue (cT3N2bM0, cStage ⅣA)at a previous hospital. Seven years postoperatively, bilateral osteoradionecrosis of the mandible developed, and the patient was referred to our department for further treatment. Since the lesions were extensive, we planned reconstructive surgery using the TruMatch® system in collaboration with the plastic surgery department of our hospital. Surgery was performed precisely and accurately according to the preoperative simulation. Postoperatively, the patient's recovery was uneventful. The TruMatch® system enables us to achieve good morphological and comprehensive functional oral-maxillofacial reconstruction.

Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema.

Secondary lymphedema is a common complication of lymph node dissection or radiation therapy for cancer treatment. Conventional therapies such as compression sleeve therapy, complete decongestive physiotherapy, and surgical therapies decrease edema; however, they are not curative because they cannot modulate the pathophysiology of lymphedema. Recent advances reveal that the activation and accumulation of CD4+ T cells are key in the development of lymphedema. Based on this pathophysiology, the efficacy of pharmacotherapy (tacrolimus, anti-IL-4/IL-13 antibody, or fingolimod) and cell-based therapy for lymphedema has been demonstrated in animal models and pilot studies. In addition, mesenchymal stem/stromal cells (MSCs) have attracted attention as candidates for cell-based lymphedema therapy because they improve symptoms and decrease edema volume in the long term with no serious adverse effects in pilot studies. Furthermore, MSC transplantation promotes functional lymphatic regeneration and improves the microenvironment in animal models. In this review, we focus on inflammatory cells involved in the pathogenesis of lymphedema and discuss the efficacy and challenges of pharmacotherapy and cell-based therapies for lymphedema.

[Oral Function Restoration via Two-Stage Reconstructive Treatment of an Extensive Maxillary Defect Following Maxillectomy].

Recently, the number of survivors that had oral cancer has increased, but deterioration in the quality of life of patients concerning oral function and cosmetic appearance has become problematic. Prosthodontic dentures usefully treat jaw defects after maxillary resection for cancer, but advances in microsurgery have rendered the possibility to reconstruct maxillary defect and oral cavity using a microvascular flap. Here, we describe 2-stage treatment after 35 years postoperatively. We restored the maxillofacial function using microvascular flaps and partial denture. The patient was a 59-year-old woman who underwent left lateral maxillectomy 35 years previously to treat an advanced left maxilla gingival carcinoma. A maxillary prosthesis was applied, requiring repeated adjustments and refabrications. The patient visited to obtain improvements for oral and maxillofacial functions and long-term quality of life. The left maxillary bone defect was 45×50 mm in area. Collaborating with the Department of Plastic and Reconstructive Surgery, the patient underwent reconstructive treatment using a microvascular forearm flap and partial denture. The patient's progress was excellent; eating, swallowing, and articulation improved. For 1 year postoperatively, the patient was satisfied with the results.

[A Case of Tongue Carcinoma with Malignant Transformation Caused by the Pandemic].

In April 2020, a state of emergency was declared because of the pandemic, and the public was instructed to refrain from leaving their homes. Consequently, this stirred up anxiety about visiting medical institutions. Here, we describe a case of tongue carcinoma that developed from an oral precancerous lesion into a malignant transformation owing to the effects of refraining from medical examinations caused by the pandemic. The patient was a 62-year-old woman. In March 2020, the patient became aware of a mass at the tongue's margin and was referred to our department. An excisional biopsy was performed, and a diagnosis of inflammatory change was made. The following month, a white ulcerative lesion was found, and another excisional biopsy was performed; therefore, a diagnosis of left tongue leukoplakia without epithelial dysplasia was made. The patient was scheduled for surgery; however, refused treatment and consultation because of the pandemic. In September 2021, the patient revisited our department on her own volition because an ulcerative lesion with indistinct borders and induration was found at the left lingual margin. Upon close examination, a diagnosis of left tongue squamous cell carcinoma(cT2N2bM0, Stage ⅣA)was made. In October 2021, radical tumor resection and reconstruction were performed. After 8 months postoperatively, the patient is currently well.

Safety and efficacy of secondary mandibular reconstruction using a free osteo-cutaneous fibula flap after segmental mandibular resection: a retrospective case-control study.

BACKGROUND: Free osteocutaneous fibula flap (FFF) is currently considered the best option for segmental mandibular reconstruction; however, there are only a few reports comparing secondary with primary reconstructions using FFF. This study aimed to evaluate the safety and efficacy of secondary mandibular reconstruction using FFF when compared with primary mandibular reconstruction. METHODS: From October 2018 to February 2020, patients who underwent mandibular reconstruction using FFF after segmental mandibulectomy were retrospectively reviewed. The size and location of the mandibular defect, the segment length and number of osteotomies in the fibula, types of the mandibular plating system, kinds and laterality of the recipient vessels were recorded from the surgical notes. Flap survival, duration of nasogastric tube use, and implant installation after reconstruction were recorded as postoperative evaluation indices. RESULTS: Twelve patients underwent mandibular reconstruction using FFF during the study period. There were no significant differences in demographic characteristics other than body mass index between the primary (n = 8) and secondary (n = 4) reconstruction groups. No significant differences were observed in the size and location of defects, the segment length and number of osteotomies in the fibula, and the types of mandibular plating system. There was no significant difference in the kinds of recipient vessels; however, the laterality of recipient vessels was ipsilateral in all cases of primary reconstructions and contralateral in all cases of secondary reconstructions. Three out of eight patients with primary FFF reconstruction developed partial flap necrosis. Four patients in the secondary FFF reconstruction group achieved complete flap survival. The duration of use of the nasogastric tube and implant installation after reconstruction was comparable between the two groups. CONCLUSION: Safe and effective secondary mandibular reconstruction can be performed in this clinical case study using FFF.

Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice.

Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 × 105 ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.

[A Case of Early Detection and Treatment Applicable to Squamous Cell Carcinoma of the Palate Detected by Oral Cancer Mass Screening in Izumo 2019].

Treatment of oral cancer is based on radical resection and reconstructive surgery. Surgery causes impairment of maxillofacial morphology and function, including chewing and eating difficulties, and dysarthria. It is necessary to restore the maxillofacial morphology and function by reconstructive surgery and use of prostheses. Therefore, early detection and treatment are required to reduce these disabilities associated with oral cancers. Here, we report a case of oral cancer that was detected early by our oral cancer mass screening program in Izumo, Japan, in 2019. A 73-year-old woman presented with a reddish ulcerative region in the palate. Cytological screening indicated positive-suspected low squamous intraepithelial neoplasia (LSIL). The patient was diagnosed as squamous cell carcinoma of the palate(cT1N0M0, StageⅠ)in our hospital. We performed radical resection of the palate tumor and immediate reconstruction using a vascularized radial forearm flap. The clinical course was good and oral function was fully restored. It is important for oral surgeons to publicize and raise awareness of oral cancer, and to continue oral cancer mass screening programs.

A new lower eyelid reconstruction using transverse facial artery perforator flap based on an anatomical study.

With the ageing of the global society, the demand for lower eyelid reconstruction following malignant skin tumour resection is increasing. For decades, flaps that require excessive dissection have been used to reconstruct relatively large lower eyelid defects. A new, less invasive option is needed for elderly patients. We present a new surgical technique using a transverse facial artery perforator flap. Records of 11 patients who underwent lower eyelid reconstruction with transverse facial artery perforator flaps after malignant skin tumour resection were reviewed. The mean age of the patients was 85.7 ± 6.7 years. Six patients underwent surgery under local anaesthesia and five under general anaesthesia. Malignant skin tumours were resected with 4-10 mm of the surrounding skin, depending on the tumour type. An ipsilateral transverse facial artery perforator flap was raised to cover the defect. Primary reconstructions were achieved in all cases. The median follow-up period was 13 (range, 9-33) months. Two minor complications occurred during the follow-up period: pyogenic granuloma (n = 1) and temporary ocular pain and conjunctivitis (n = 1). The incidence of complications and the results of the functional and aesthetic evaluation based on the modified patient-reported outcome measure showed no significant differences between the two different anaesthesia groups. To the best of our knowledge, this is the first report to describe the use of a transverse facial artery perforator flap for lower eyelid reconstruction. The flap may be an effective option for lower eyelid reconstruction in elderly patients to achieve good functional and aesthetic outcomes with low risk and minimal invasion.

An esthetic, functional, and low-invasive lower red lip reconstruction using a mucosal perforator flap: A case report.

Key Clinical Message: Lower red lip reconstruction using a mucosal perforator flap is low-invasive and adheres to the concept of "like with like." The location of the mucosal perforator can easily be detected using color Doppler ultrasound. Abstract: Lip reconstructions should provide results of a high degree regarding both functionality and esthetics. We describe a case of lower red lip reconstruction using a mucosal perforator. An 81-year-old man complained of repeated bleeding from a submucosal venous malformation on his lower red lip, and surgery was performed under local anesthesia. The venous malformation was completely resected. A 4 cm × 2 cm triangle-shaped flap containing a mucosal perforator, identified using color Doppler ultrasound preoperatively, was designed in the lower red lip adjacent to the defect. The perforator flap was raised in the submucosal layer, and the defect was covered with the flap in an advancement manner. The flap transfer-related defect was closed, and at the one-year follow-up examination, no recurrence, drooling, or speech impediment was observed. In this case, excellent functional and esthetic results were achieved following the low-invasive reconstruction using a mucosal perforator flap.

Role and Function of Mesenchymal Stem Cells on Fibroblast in Cutaneous Wound Healing.

Skin wounds often repair themselves completely over time; however, this is true only for healthy individuals. Although various studies are being conducted to improve wound-healing therapy outcomes, the mechanisms of wound healing and regeneration are not completely understood yet. In recent years, mesenchymal stem cells (MSCs) have been reported to contribute significantly to wound healing and regeneration. Understanding the function of MSCs will help to elucidate the fundamentals of wound healing. MSCs are multipotent stem cells that are used in regenerative medicine for their ability to self-renew and differentiate into bone, fat, and cartilage, with few ethical problems associated with cell harvesting. Additionally, they have anti-inflammatory and immunomodulatory properties and antifibrotic effects via paracrine signaling, and many studies have been conducted to use them to treat graft-versus-host disease, inflammatory bowel disease, and intractable cutaneous wounds. Many substances derived from MSCs are involved in the wound-healing process, and specific cascades and pathways have been elucidated. This review aims to explain the fundamental role of MSCs in wound healing and the effects of MSCs on fibroblasts.

Topical odour management in burn patients.

Preventing microbial colonization or infections that cause offensive smells may lead to odor reduction. As both anaerobic and aerobic bacteria cause the release of malodor from wounds, the most direct way of avoiding or eliminating wound odor is to prevent or eradicate the responsible infection through the debridement of necrotic tissues. However, some burn patients with malodorous wounds are unable to undergo debridement due to systemic conditions, especially in the acute stage. Moreover, the optimal drug doses and dressings to ensure the efficacy and cost-effectiveness of odorous burn wound management is unclear. The purpose of this commentary is to outline the odor management options available for burn patients, focusing on topical strategies. Numerous potential therapies for treating odorous wounds after burn injuries are suggested.

Fournier's Gangrene With Subcutaneous Emphysema of the Thigh Caused by Air Inflow Associated With a Rectovaginal Fistula: A Case Report of Pseudo-gas Gangrene.

INTRODUCTION: Rectovaginal fistulas (RVFs) are abnormal connections between the rectum and vagina. CASE REPORT: A 61-year-old female patient was admitted to the authors' hospital with swelling, extending from the left thigh to the left lower abdomen and crepitus. An axial computed tomography scan showed air in the soft tissue of the left thigh, left buttock, perineal region, and left lower abdomen. Gas gangrene was suspected. Accordingly, the patient was administered meropenem, clindamycin, and vancomycin and underwent emergency debridement. An intraoperative examination revealed necrotizing fasciitis in the left buttock but no inflammatory signs in the thigh. On postoperative day 8, fecal matter was discharged from the patient's vagina, and an RVF was detected by colon fiberscopy. The patient underwent resurfacing surgery with a free skin graft, and a colon stoma was fashioned 15 days after the primary surgery. The patient was discharged on day 14 following surgery with wound healing. CONCLUSION: The existence of free air in subcutaneous tissue combined with an infection, particularly in the extremities, is generally suggestive of gas gangrene. In the present case, subcutaneous gas was not caused by gas gangrene but rather by air inflow from an RVF. Appropriate treatment of the RVF was necessary to avoid the exacerbation of Fournier's gangrene and prevent necrosis spreading to the thigh.

Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence.

Once scar tissues mature, it is impossible for the surrounding tissue to regenerate normal dermal tissue. Therefore, it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation. Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing. However, the underlying mechanisms of hypertrophic scar development are poorly understood. The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation, focusing on strategies excluding therapeutic agents of internal use. Treatment aimed at molecular targets, including cytokines, will be future options to prevent and treat hypertrophic scars. More basic studies and clinical trials, including combination therapy, are required to investigate the mechanisms and prevent hypertrophic scar formation.

Advances in surgical applications of growth factors for wound healing.

Growth factors have recently gained clinical importance for wound management. Application of recombinant growth factors has been shown to mimic cell migration, proliferation, and differentiation in vivo, allowing for external modulation of the healing process. Perioperative drug delivery systems can enhance the biological activity of these growth factors, which have a very short in vivo half-life after topical administration. Although the basic mechanisms of these growth factors are well understood, most have yet to demonstrate a significant impact in animal studies or small-sized clinical trials. In this review, we emphasized currently approved growth factor therapies, including a sustained release system for growth factors, emerging therapies, and future research possibilities combined with surgical procedures. Approaches seeking to understand wound healing at a systemic level are currently ongoing. However, further research and consideration in surgery will be needed to provide definitive confirmation of the efficacy of growth factor therapies for intractable wounds.

Lymphovenous anastomosis for the treatment of persistent congenital chylothorax in a low-birth-weight infant: A case report.

RATIONALE: Chylothorax remains a poorly understood phenomenon, and no optimal treatment or guidelines have been established. This is the first report of treating congenital chylothorax and lymphedema in a low-birth-weight infant by lymphovenous anastomosis (LVA). PATIENT CONCERNS: We report a case of successful LVA for persistent congenital chylothorax and lymphedema resistant to other conservative therapies. DIAGNOSIS: The diagnosis of chylothorax was confirmed by the predominance of lymphocytes in the pleural fluid draining from the chest tube. In addition, the infant developed oliguria and generalized lymphedema. INTERVENTIONS: LVA under local anesthesia combined with light sedation was performed at his medial thighs and left upper arm. OUTCOMES: Although his subcutaneous edema markedly improved, the decrease in chest tube drainage was gradual. No additional treatment was required. LESSONS: LVA is of considerable value as a surgical treatment option in the setting of persistent congenital chylothorax and lymphedema, because LVA is a less invasive procedure.

Foot reconstruction with the superficial circumflex iliac artery perforator flap under local anesthesia: Two case reports.

RATIONALE: The superficial circumflex iliac artery perforator (SCIP) free flap is a popular method used in foot reconstruction. Although the SCIP flap has a relatively short pedicle and does not require intramuscular dissection, general anesthesia is largely preferred for SCIP flap reconstruction. We report 2 cases with the free SCIP flap for skin and soft tissue reconstruction of the foot under local anesthesia. PATIENT CONCERNS: Case 1 was a 34-year-old man sustained a crush injury to the dorsal foot, resulting in a soft tissue defect with bone and tendon exposure. Case 2 was a 41-year-old man with type 2 diabetes was referred to our division for an intractable ankle wound after surgery for a calcaneal bone fracture. DIAGNOSIS: The diagnosis was intractable wounds on feet caused by trauma and surgery. Patients were unable to receive general anesthesia because of asthma or elevated liver enzymes. INTERVENTIONS: Two patients with tissue defects on their feet were treated with SCIP flaps under local anesthesia. Fifteen milliliter of 0.5% bupivacaine was injected for ankle block. SCIP flaps were harvested after injecting 10 to 15 mL of 1% lidocaine combined with epinephrine around the flap incisions. OUTCOMES: No complications related to the use of local anesthesia developed during the operation or postoperatively. Two flaps survived and fully took without complications. LESSONS: With proper local anesthesia, successful foot reconstruction with a free SCIP flap was possible. This method can be considered a sufficient option for foot reconstruction for patients unable to receive general anesthesia.

Risk Factors for Postoperative Complications among the Elderly after Plastic Surgery Procedures Performed under General Anesthesia.

BACKGROUND: The frequency of surgery involving elderly patients has been increasing. The use of free tissue transfers in the elderly has been examined previously (Howard et al., 2005, Hwang et al., 2016, Grammatica et al., 2015, Serletti et al., 2000, and Sierakowski et al., 2017), whereas there have not been any such studies of plastic surgery procedures. We evaluated the risk factors for complications after plastic surgery procedures performed under general anesthesia in patients aged ≥75 years. METHODS: The cases of patients aged ≥75 years who underwent plastic surgery procedures under general anesthesia at the Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, between 2009 and 2016 were reviewed retrospectively. Multiple logistic regression analysis was used to identify the risk factors for postoperative complications. RESULTS: Two hundred and sixty-three cases were reviewed. Complications were seen in 137 patients. Age was not predictive of complications. The risk factors included a serum albumin level of <2.8 g/dl (odds ratio (OR): 2.96), an operative time of ≥120 min (OR: 6.22), and an American Society of Anesthesiologists performance status of ≥3 (OR: 2.39). CONCLUSIONS: Age is not contraindication for surgery in the elderly. It is important to assess comorbidities and perform surgical procedures as soon as possible to shorten the surgical period.