Satoru Sasaki

Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells.

Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the statins) that inhibit the synthesis of mevalonic acid are in wide use for treatment of hypercholesterolemia. Although antitumor effects on a variety of cell types have been reported for statins, the effect of simvastatin (one of the statins) on human melanoma cell lines is not known. Here, we report antitumor effects of simvastatin on human melanoma cell lines. We treated human melanoma cell lines, A375M, G361, C8161, GAK, and MMAc with simvastatin in various concentrations for 1 to 3 days. To investigate the antitumor effect of simvastatin, we analyzed cell viability, morphologic changes, reversibility of inhibition by geranylgeranyl pyrophosphate and farnesyl pyrophosphate, apoptosis and the cell cycle. Simvastatin treatment reduced cell viability in all five melanoma cell lines. The different melanoma cell lines, however, displayed different sensitivities to simvastatin. The addition of geranylgeranyl pyrophosphate to A375M and G361 cells in the presence of simvastatin completely restored the viability of cells, but the addition of farnesyl pyrophosphate did not. DNA fragmentation assay showed that simvastatin induced apoptosis in A375M and G361 cells. Simvastatin caused a G1 arrest in G361 and MMAc cells. Consistent with the cell cycle arrest, simvastatin caused an increase in the mRNA levels of p21 and p27 on G361 and MMAc cells.We conclude that simvastatin has an antitumor effect on human melanoma cells in vitro via apoptosis and cell cycle arrest. These results suggest that simvastatin may be an effective anticancer drug for malignant melanoma.

New grading system for patients with treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a congenital, craniofacial disorder affecting the development of structures derived from the first and second branchial arches. The associated clinical features and their severity are variable. Therefore, we reasoned that objective assessment of the clinical features and their severity in TCS is necessary to plan the treatment and to evaluate the outcome. We hereby propose a new grading system for Treacher Collins syndrome (TCS). Since 1978, 16 patients have been diagnosed with TCS. Eleven out of the 16 TCS patients, for whom we were able to estimate the severity of the clinical features in each region, and to make an objective assessment of the therapeutic outcomes, were selected. By allocating points according to the degree of severity of the clinical features in each region, then summing them up and categorizing them, we classified the overall clinical features into 3 grades. The severity increases from grades I to III. In summary, there were 3 patients of grade I, 4 patients of grade II and 4 patients of grade III. Distinctive differences regarding the degree of severity of the clinical features were clearly observed between each grade. We propose a new TCS grading system and applied it to 11 patients. We believe that this system may be useful for planning treatment and to evaluate the outcome in TCS patients.

How do the type and location of a vascular malformation influence growth in Klippel-Trénaunay syndrome?

Background: Although Klippel-Trénaunay syndrome is a mixed vascular malformation characterized by abnormal growth in the extremities, no uniform diagnostic criteria have been established because of the variety in its manifestation. Consequently, no anatomical analysis based on a comparison study has been reported. In this study, the authors determine the frequency of various vascular malformations and abnormal growth and assess any statistical relationship between vascular malformation type/location and abnormal growth in terms of length and girth. Methods: Thirty-five patients with Klippel-Trénaunay syndrome satisfying the criteria proposed by Oduber et al. in 2008 were enrolled. The type and location of the vascular malformation and abnormal circumferential growth were assessed by magnetic resonance imaging and ultrasonography. Bone girth was assessed by axial magnetic resonance imaging/computed tomography. Plain radiographs of the long bones were used to measure growth in length. Results: The spectrum of vascular types was similar to that in previous reports. There was no significant association between leg length and vascular malformation type or location. Leg bone circumferential hypoplasia was observed in 50 percent of cases and was significantly related to the presence of intramuscular lesions. A single venous malformation in the subcutaneous tissue was significantly associated with the presence of subcutaneous hypertrophy. Patients with intramuscular lymphatic malformations had a significantly higher frequency of muscle hypoplasia. Conclusion: The type and location of certain vascular malformations were significantly associated with abnormal subcutaneous tissue, muscle, and bone growth.

Intravenous pyogenic granuloma of the finger

Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.

«Boomerang» rectus abdominis musculocutaneous free flap in head and neck reconstruction

Immediate head and neck reconstruction after cancer resection using the “boomerang” rectus abdominis musculocutaneous (RAM) free flap was performed in 13 patients over the past 2 years. The skin paddle of the flap is designed as a boomerang shape based on the anatomical construction of the dominant perforators from the inferior epigastric vascular system. A versatile technique of the boomerang RAM flap provides effective use for reconstruction of the complex defects at the skull base, orbital, nasal cavity, paranasal sinuses, oropharynx, palate, buccal mucosa, tongue, floor of mouth, and neck. It also allows a reconstructive surgical team to elevate the flap simultaneously with a head and neck surgical team before the size and location of the defect are exactly determined and greatly reduces operating time. This flap will be a routine technique for immediate head and neck reconstruction after cancer resection.

Modification of thoracoscopy in pectus excavatum: insertion of both thoracoscope and introducer through a single incision to maximise visualisation.

Our modification of the Nuss procedure includes insertion of both the introducer and the thoracoscope through the same skin incision, which enables continuous visualisation of the tip of the introducer during blunt dissection across the mediastinum. From January 2001 to January 2005 we studied 32 consecutive patients whose ages ranged from 3 to 30 years. They had all undergone the modified procedure. The mean operating time was 1 hour 44 minutes (range 43 minutes–4 hours 20 minutes). Blood loss was less than 10 ml. There were no intraoperative bleed complications. The modification that we devised may minimise the risk of cardiothoracic and vascular injuries and the procedure is safe.

Microsurgical reconstruction of the digestive tract following pharyngolaryngectomy and total esophagectomy.

Total pharyngoesophageal reconstruction has remained a challenging field in digestive surgery. During the past 3 years, the authors performed six microsurgical reconstructions of the digestive tract following pharyngolaryngectomy and total esophagectomy due to a multiple cancer or skip metastasis. Digestive continuity was restored using a combination of a pulled-up gastric pedicle and free jejunal transfer in 2 patients, and an elongated gastric pedicle with microvascular augmentation in 4 patients. One elongated gastric pedicle developed partial necrosis, and a free jejunal graft was placed additionally. One patient suffered from respiratory dysfunction and died 1 month after surgery. Postoperative radiographic examination showed a good swallowing mechanism without reflux and stasis in all patients. Microvascular surgery contributes to the successful reconstruction of the digestive tract following extensive pharyngolaryngoesophagectomy.

Merkel cell carcinoma of the face: an analysis of 16 cases in the Japanese

BACKGROUND There is no agreement regarding a staging system and optimal treatment of Merkel cell carcinoma. Some centres have reported results from larger series of patients, but these do not include Asian or Japanese centres. OBJECTIVE The purpose of this study was to retrospectively review our experience with the surgical treatment of MCC of the face in the Japanese and to study its management and outcome using the staging system described by Clark et al. METHODS We report our experiences with 16 cases between 1991 and 2004. Patients and tumour characteristics, treatment variables and outcome were analysed. RESULTS The follow-up periods ranged from 1 to 180 months. The average was 32.6 months and the median was 17.5 months. The relapse-free survival for all patients was 51% at 2 years. The relapse-free survival was 80% for the patients with Stage I and 33% with Stage II at 2 years. CONCLUSION This staging system was suggested to reflect prognosis although the number of patients in this series was small. Sentinel lymph node biopsy should be considered to determine the accurate nodal staging, and patients with MCC of the head and neck may be treated according to the revised staging system by Clark et al.

Ethanol sclerotherapy with ‘injection and aspiration technique’ for giant lymphatic malformation in adult cases

Ethanol is a commonly used sclerosant for lymphatic malformation (LM), and recent evidence has shown that macrocystic LMs respond very well to percutaneous sclerotherapy. However, the volume of absolute ethanol that can be injected safely is small (0.5-1 ml/kg), and that is the reason it is often ineffective in extensive LM. We report two cases of giant LM with occasional high fever and pain or abnormal gait. To overcome dose limitation and to prevent systematic toxicities, we performed both injection of absolute ethanol and aspiration of it after 5 min exposure to LM. The injected maximum ethanol dose per one session is 70-260 ml and no systemic complication occurred. The 1-3 sessions of those procedures reduced the frequency of high fever and improved the swelling of those lesions. The injection and aspiration technique maximises the efficacy of sclerotherapy for extensive macrocystic LM in adults.

Salvage of cartilage framework exposure in microtia reconstruction using a mastoid fascial flap

One of the common complications of microtia reconstruction with cartilage grafting is exposure of the framework. Recently, we used a mastoid fascial flap for salvage operations in two microtia patients, who had partial skin necrosis with resultant exposure of the cartilage framework. Following the excision of the necrotic skin, the anteriorly based mastoid fascial flap was elevated and transferred as a hinge flap on to the portion of the exposed framework. Split-thickness skin grafts were applied over the mastoid fascial flap. Each skin graft took well and the relief of the reconstructed ear was preserved in both cases. This salvage method has a large advantage of not leaving any visible scars on the temporal region and the reliability of its rich blood supply.