The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention.

Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.

Surgical treatment of nonuremic calciphylaxis: a case report and review of literature.

Calciphylaxis is characterized by extremely painful skin ulcers and develops in patients with or without severe kidney diseases. Herein, a female patient without renal dysfunction developed calciphylaxis in the right lower extremity and underwent successful surgical debridement and split-thickness skin grafting. Nevertheless, prompt wound evaluation and proper surgical approaches are essential.

Diagnosis and Treatment of Keloids and Hypertrophic Scars-Japan Scar Workshop Consensus Document 2018.

There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases. This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases. By contrast, Caucasians are less likely to develop keloids and hypertrophic scars, and if they do, the scars tend not to be severe. This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms. The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments, with uneven outcomes. To overcome these issues, the Japan Scar Workshop (JSW) has created a tool that allows clinicians to objectively diagnose and distinguish between keloids, hypertrophic scars, and mature scars. This tool is called the JSW Scar Scale (JSS) and it involves scoring the risk factors of the individual patients and the affected areas. The tool is simple and easy to use. As a result, even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity. The JSW has also established a committee that, in cooperation with outside experts in various fields, has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines. These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy. The Consensus Document is provided in this article. It describes (1) the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors, (2) the general treatment algorithms for keloids and hypertrophic scars at different medical facilities, (3) the rationale behind each treatment for keloids and hypertrophic scars, and (4) the body site-specific treatment protocols for these scars. We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.

Oblique lateral incision and subpectoral dissection in modified Nuss procedure minimize future breast deformity.

BACKGROUND: We experienced the occurrence of breast deformity in some young female patients who underwent a modified Nuss procedure before breast development. We studied the causes of and preventive measures for this complication. METHODS: We classified 13 prepubescent female patients who underwent our modified Nuss procedure into three groups according to the direction of the skin incision and the dissection layer for bar insertion. Four patients who underwent transverse lateral thoracic skin incision and bar insertion through a subpectoral dissection were assigned to the T/SP group, five who underwent oblique skin incision along the rib and bar insertion through a suprapectoral dissection were assigned to the O/IP group, and four who underwent oblique skin incision and subpectoral dissection were assigned to the O/SP group. Each patient in the T/SP group underwent the operation by a different surgeon, two of whom were the authors, including the first author; the first author performed all operations in the O/IP and O/SP groups. The first author evaluated the shape of the developed breasts using the frontal- and oblique-view photographs. We also investigated the location of the lateral border of the mammary gland in seven other adolescent and adult female patients using three-dimensional computed tomography images. RESULTS: Lateral depression of the breast occurred in four of eight breasts with a transverse incision, and flattening of the lowermost portion of the inframammary fold occurred in six of 10 breasts with suprapectoral dissection. None of the eight breasts with an oblique incision and subpectoral dissection exhibited deformities. The lateral border of the mammary gland was on the fifth rib in five patients and on the fifth intercostal space in two patients. CONCLUSION: An oblique lateral thoracic skin incision along the sixth rib and subpectoral dissection may reduce the occurrence of breast deformity.

A case of combined soft tissue and intraosseous venous malformation of the thumb treated with sclerotherapy using a bone marrow aspiration needle.

Vascular malformations of bone are complex lesions that can cause deformity and pain. A combined soft tissue and intraosseous venous malformation of the left thumb in a girl was treated with two sessions of ethanol sclerotherapy using a bone marrow aspiration needle under fluoroscopic guidance.

Preliminary experience with intraoperative near-infrared fluorescence imaging in percutaneous sclerotherapy of soft-tissue venous malformations.

BACKGROUND: It has recently been demonstrated that near-infrared (NIR) fluorescence imaging can be used to visualize the blood vasculature. Although sclerotherapy has been successfully used in treating venous malformations, the spread of sclerosant is difficult to monitor during sclerotherapy. OBJECTIVE: To evaluate the safety and efficacy of NIR fluorescence imaging in percutaneous sclerotherapy of soft-tissue venous malformations. METHODS AND MATERIALS: The use of NIR fluorescence imaging after administration of indocyanine green (ICG) was evaluated in duplex-guided sclerotherapy performed on 15 patients with venous malformations. The lower extremities were involved in seven, the upper extremities in four, and the face in four. RESULTS: In 13 of the 15 procedures, spotty fluorescence images were obtained, and in eight procedures, linear fluorescence images were obtained. In two patients with intramuscular venous malformations in the lower extremities, no fluorescence images were obtained. Observational depth seemed to be <1 cm below the skin surface with an ICG concentration of 0.01 mg/mL. No complications associated with ICG were observed. Adjacent tissue ulceration occurred in one patient. CONCLUSION: NIR fluorescence imaging with ICG can be a useful additional monitor for percutaneous sclerotherapy of venous malformations, especially in the face and hands, enabling noninvasive assessment of real-time spread of sclerosant.

Evaluation of the sclerotherapeutic efficacy of ethanol, polidocanol, and OK-432 using an in vitro model.

BACKGROUND: Sclerosants are used to treat vascular malformations. Owing to variations in the flow, the injected concentrations and the duration of exposure of these sclerosants are altered. Therefore, the clinical effectiveness of sclerotherapy is variable. OBJECTIVE: The objective was to evaluate the differences in clinical response, usually observed among ethanol, polidocanol, and OK-432, using an in vitro sclerotherapy model. METHODS: Endothelial cells were cultured and exposed to different concentrations of the sclerosants for 5 seconds and the remaining viable cells were counted using a MTT assay kit. Dyes were used to visualize the morphologic changes. Precipitant formation in blood was also evaluated. Finally, the degree of ICAM-1 expression, after exposure to lower concentrations of these sclerosants, was studied using immunocytochemistry. RESULTS: Only ethanol causes precipitant formation and kills almost all cells from 30% concentration. Polidocanol begins to disrupt the cell membrane from 0.0125% onward. Only OK-432 induces ICAM-1 expression. CONCLUSION: Ethanol's strong precipitant-forming effect may induce thromboembolism, thus enhancing sclerosis. Polidocanol's endothelial cell-lysing effect was clearly documented. OK-432 may mediate its effect by inducing inflammatory response of the endothelium via ICAM-1 expression. This in vitro model may be useful in evaluating other sclerosants as well.