Masamitsu Kuwahara

Experience with surgical treatment of hidradenitis suppurativa.

The authors report their experience with 23 sites of hidradenitis suppurativa, including cases with musculocutaneous flap repair, and discuss the surgical methods applied. Twenty-three sites in 19 patients with chronic inflammatory skin lesions were reviewed. The lesions were divided into two groups: The limited group was comprised of mild lesions, which appear isolated and have limited abscesses without sinus tract formations. The severe group was compromised of severe lesions, which included diffuse, multiple abscesses with severe sinus tract formation and fibrosis. Nine sites were limited and 14 sites were severe. After resecting the lesion, the defect was covered with a split-thickness skin graft (four sites were limited, nine sites severe), a musculocutaneous flap (five sites severe), primary closure (four sites limited), and a local skin flap (one site limited). In six sites in 6 severe-group patients, local recurrence occurred. The local recurrence rate differed significantly between the limited and the severe groups. The reason for this may be because the lesions in the limited group could be resected completely, whereas the lesions in the severe group were diffuse and total resection was sometimes difficult for various reasons. The method of surgical repair did not affect the local recurrence rate. In recurrent cases, four sites treated with skin grafting required further surgical treatment, and two sites treated with musculocutaneous flaps were controlled with oral antibiotics. In conclusion, sufficient resection of the lesion is the most important issue in treating follicular occlusion triad disease. In lesions that can be resected completely, the surgical procedure to cover the lesions should be selected to suit the size and site of the defect. However, in cases that cannot be resected completely, a musculocutaneous flap is recommended instead of a skin graft for enhanced postoperative management of the recurring wound, and its contribution to aesthetic and functional improvement.

Expression of desmoglein I and plakoglobin in skin carcinomas

Reduction or absence of cell‐cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell‐cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E‐cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells. In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Pagets disease and Bowens disease by an immunofluorescence method. In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells. In carcinoma in situ of Pagets disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Pagets disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowens disease, the expression of desmoglein I was reduced in the clumping cells and dyskeratotic cells. These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.

Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype–genotype correlation in Japanese patients with pachydermoperiostosis

BACKGROUND Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. OBJECTIVE We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). METHODS Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. RESULTS From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. CONCLUSION We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.

Difference of Molecular Response to Ischemia???Reperfusion of Rat Skeletal Muscle as a Function of Ischemic Time: Study of the Expression of p53, p21WAF-1, Bax Protein, and Apoptosis

The authors investigated the expression of p53, p21WAF-1, Bax protein, and apoptosis to elucidate the cellular response to ischemia–reperfusion of skeletal muscle using the rat lower limb model. The rat left lower limb was dissected in the inguinal region, isolating the bony femoral muscles, and the femoral vessels were clamped to produce an ischemic condition. After 3 or 6 hours, the clamps were removed and the gastrocnemius muscle was resected at various times up to 72 hours after reperfusion. Five specimens of the muscle were obtained at each time point from 5 rats. When any rat died during the study, additional rats were used until 5 specimens could be obtained from 5 rats at each time point. The expression of three proteins was detected by Western blot analysis. The apoptotic cells were detected using terminal deoxytransferase-mediated dUDP (deoxyuridine[-5′]diphosphate) nick-end labeling assay. Histopathological study showed severe interstitial edema and leukocyte infiltration at 6 hours of ischemia compared with 3 hours of ischemia. Moreover, at 6 hours of ischemia, muscle fiber fragmentation was observed at 72 hours after reperfusion whereas no fragmentation was found at 3 hours of ischemia. At 3 hours of ischemia, p53 and p21WAF-1 accumulated after reperfusion, and there was a time lag in the time of onset of elevation and the peak time point between these two proteins. The level of Bax protein did not elevate and the rate of apoptotic cells did not increase. At 6 hours of ischemia, p53 and p21WAF-1 also accumulated, but the kinetics of p21WAF-1 were similar to that of p53 in the time of onset of elevation and the peak time point after reperfusion. In addition, the level of Bax protein increased and apoptosis was induced. These results demonstrated that p53 and p21WAF-1 accumulated after 3 and 6 hours of ischemia of skeletal muscle during reperfusion. Moreover, it was demonstrated that the kinetics of induced p53, p21WAF-1, and Bax protein differ between 3 hours and 6 hours of ischemia, and it is speculated that this difference plays an important role in determining the consequence of the cell exposed to ischemia.

Mortality and Recurrence Rate After Pressure Ulcer Operation for Elderly Long-term Bedridden Patients

We operated on 16 sacral pressure ulcers in elderly and long-term residential patients who were immobile as a result of cerebral vascular disease. The mean age of patients was 76 years. Eight ulcers were treated with local fascial flaps and 8 by simple closure. The follow-up period was from 1 to 4 years. Recurrence and mortality rates were examined retrospectively. In the 16 patients, recurrence occurred in 37.5%, and 43.8% died without recurrence. The recurrence rate was 37.5% for local fascial flaps and 37.5% for simple closure. Overall mortality was 68.8% in the follow-up period. Because postoperative death was common, we should not only focus on reducing local pressure but also pay attention to any underlying disease. Because of this high mortality rate, the least invasive procedure possible should be used. Because the recurrence rate of simple closure was the same as for local fascial flaps, simple closure should be considered as a reconstructive method.

E-cadherin expression in wound healing of mouse skin

Background: E‐cadherin has been studied extensively in other systems but little attention has been paid to its role in wound healing. We investigated E‐cadherin expression in epithelial wound healing in vivo by focusing on the migrating cells in the epithelial tongue and the mitotic cells in the non–injured side apart from the original wound edge.

An evaluation of functional improvement following surgical corrections of severe burn scar contracture in the axilla

This report present an evaluation 13 consecutive cases of severe burn scar contracture of the axilla and investigates the factors that influence functional improvement. The operation was performed at various times during the period from 3 months to 63 years after the initial burn wound healed. The active range of shoulder abduction before the operation in these patients was restricted to 30-90 degrees. The scar contractures in the axilla were released in all cases and the defects of the axillary region were covered with musculocutaneous flaps or fasciocutaneous flaps. Following operation rehabilitation was performed with the range of shoulder abduction had reached a plateau. The relations between the improved range of shoulder abduction, time to reach a stable range of abduction, patient age and duration of illness in each patient are discussed. Patient with long post-injury periods required a longer time to reach a stable range of abduction. Furthermore, the patients with an extremely long period before operation had difficulties such as nerve injury or stiff joint which restricted improvement. In conclusion, adequate surgical treatment in early period after occurrence of contracture is desirable for burn scar contracture of the axilla.

Hard-palate mucosal graft in the management of severe pincer-nail deformity.

It is well recognized that a hard-palate mucosal graft offers adequate support with less shrinkage than full-thickness skin grafts and minimum keratinization, even when grafted under dry conditions.1–3 In addition, its thickness and firmness are similar to those of the nail bed. We thought that these characteristics of hard-palate mucosa may be applicable to nail-bed defects, and chose to use the graft as a covering material for the repair of a nail-bed defect after resecting subungual exostosis.4 We found that compared with a free-skin graft, the hard-palate mucosal graft provided good coverage of the nail-bed defect. As in most clinics, we encounter various types of nail deformities on a daily basis, including pincer nail. A severe case of pincer nail reveals a tubelike deformity of the nail plate in which the overcurvature increases along the axis from in a proximal-to-distal direction.5 The nail bed and nail-bed tissue generally shrink, especially at distal sites, resulting in a very narrow nail bed.6 To correct the pincer-nail deformity, the narrow nail bed must be spread. However, in severe cases, the shrunken nail-bed tissue may not be large enough to cover the entire area of the spread nail bed, which results in a nail-bed defect. In this case, a material that offers less shrinkage, provides rigid support, and maintains a flattened and spread nail bed must be used to cover the defect. We describe the use of a hard-palate mucosal graft in the correction of severe pincer-nail deformity.

Usefulness and Limitations of Artificial Dermis Implantation for Posttraumatic Deformity

We have previously reported the use of artificial dermis implantation to cover exposed major vessels and to correct a depressed region after tissue resection and bone deformity with satisfactory results. In this paper, we present cases with depressed lesions and adhesive lesions after trauma, treated with artificial dermis implantation. Artificial dermis (Terudermis®, Terumo Co. Ltd., Tokyo, Japan) was implanted in 12 cases of posttraumatic deformity. Eight of the 12 cases involved a depressed lesion, and the other four involved adhesive lesions. There was no postoperative infection or allergic reaction in any of the patients. Improvement of the deformity was obtained in all cases, but the degree of volume reduction in traumatic cases is likely to be more severe than that in the non-traumatic cases previously reported. In conclusion, artificial dermis implantation is an easy, safe, and useful method to correct a posttraumatic deformity, such as a depression or an adhesion, although it is important to note that depressions require overcorrection in order to obtain satisfactory results, as compared with non-traumatic cases treated with artificial dermis.

Preshaped Hydroxyapatite Tricalcium-Phosphate Implant Using Three-Dimensional Computed Tomography in the Reconstruction of Bone Deformities of Craniomaxillofacial Region

We prepared solid life-sized models and templates of implants based on three-dimensional computed tomography data in six cases with a bone deformity of the craniomaxillofacial region. After simulation surgery using these models and templates, the preshaped hydroxyapatite-tricalcium phosphate (HAP-TCP) implants were prepared to fill in the facial bone defects, and implantation was performed. Consequently, implants fitted the individual bone defects, and satisfactory facial contouring was obtained in five cases. In one case with severe cutaneous scarring in the grafted site, it was necessary to reduce the volume of the preshaped HAP-TCP implant during surgery. In conclusion, the three-dimensional, solid, life-sized model and template are useful for preoperative detailed simulation, and the use of preshaped HAP-TCP implants based on the template probably contributes to successful reconstruction of complex facial bone deformities and to the reduction of surgical invasion, resulting in achievement of better results.