PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.
Actins ; Adenoviridae ; Cicatrix ; Collagen ; Extracellular Matrix ; Extracellular Matrix Proteins ; Genes, Neoplasm ; Genetic Therapy ; Immunohistochemistry ; Matrix Metalloproteinase 1 ; Pliability ; Relaxin ; RNA, Messenger ; Therapeutic Uses ; Tissue Inhibitor of Metalloproteinase-1

BACKGROUND: Relaxin is a transforming growth factor β1 antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. METHODS: Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. RESULTS: Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. CONCLUSION: Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated.
Adenoviridae* ; Cicatrix* ; Genetic Therapy ; Pliability ; Relaxin* ; Swine ; Therapeutic Uses ; Transforming Growth Factors

BACKGROUND: Functional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection. METHODS: Patients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy. RESULTS: Among the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy. CONCLUSIONS: The results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.
Facial Expression ; Facial Nerve* ; Follow-Up Studies ; Head ; Humans ; Neck ; Neurilemmoma ; Quality of Life ; Radiotherapy ; Salivary Gland Neoplasms ; Sural Nerve* ; Survival Rate ; Transplants*

BACKGROUND: Reconstruction of ischial pressure sore defects is challenging due to extensive bursas and high recurrence rates. In this study, we simultaneously applied a muscle flap that covered the exposed ischium and large bursa with sufficient muscular volume and a profunda femoris artery perforator fasciocutaneous flap for the management of ischial pressure sores. METHODS: We retrospectively analyzed data from 14 patients (16 ischial sores) whose ischial defects had been reconstructed using both a profunda femoris artery perforator flap and a muscle flap between January 2006 and February 2014. We compared patient characteristics, operative procedure, and clinical course. RESULTS: All flaps survived the entire follow-up period. Seven patients (50%) had a history of surgery at the site of the ischial pressure sore. The mean age of the patients included was 52.8 years (range, 18-85 years). The mean follow-up period was 27.9 months (range, 3-57 months). In two patients, a biceps femoris muscle flap was used, while a gracilis muscle flap was used in the remaining patients. In four cases (25%), wound dehiscence occurred, but healed without further complication after resuturing. Additionally, congestion occurred in one case (6%), but resolved with conservative treatment. Among 16 cases, there was only one (6%) recurrence at 34 months. CONCLUSIONS: The combination of a profunda femoris artery perforator fasciocutaneous flap and muscle flap for the treatment of ischial pressure sores provided pliability, adequate bulkiness and few long-term complications. Therefore, this may be used as an alternative treatment method for ischial pressure sores.
Arteries* ; Estrogens, Conjugated (USP) ; Follow-Up Studies ; Humans ; Ischium ; Perforator Flap* ; Pliability ; Pressure Ulcer* ; Recurrence ; Retrospective Studies ; Surgical Procedures, Operative ; Wounds and Injuries

Hepatocyte growth factor (HGF) is a potent angiogenic factor that can stimulate the production of blood vessels in ischemic tissue. We investigated whether gene therapy using HGF-expressing adenovirus could enhance skin flap survival. Sprague-Dawley rats were randomly divided into three groups. Rats were subdermally injected with HGF-expressing adenovirus (HGF virus group), recombinant HGF (rhHGF group), or phosphate buffered saline (PBS group) 2 days before and immediately after 3 x 9 cm caudal flap elevation. The survival area of the skin flap, the ratio of blood flow, CD31-positive vessels and, VEGF expression were examined. Skin flap viability was significantly increased in the HGF virus group compared to the rhHGF and PBS groups (71.4% +/- 5.9%, 63.8%+/- 6.4%, and 39.2% +/- 13.0%, respectively) (P = 0.025). Furthermore, the blood flow ratio was significantly increased in the HGF virus group. In the HGF virus group, the number of CD31-positive vessels and vascular endothelial growth factor (VEGF) expression were significantly increased. Gene therapy using HGF-expressing adenovirus increase VEGF expression, the number of viable capillaries, and blood flow to the flap, thereby improving skin flap survival.
Adenoviridae/genetics ; Animals ; Genetic Therapy/*methods ; Graft Survival/genetics ; Hepatocyte Growth Factor/biosynthesis/*genetics ; Male ; Models, Animal ; Neovascularization, Physiologic/*genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reconstructive Surgical Procedures ; Skin Transplantation/*methods ; Surgical Flaps/*surgery

BACKGROUND: Robots have allowed head and neck surgeons to extirpate oropharyngeal tumors safely without the need for lip-split incision or mandibulotomy. Using robots in oropharyngeal reconstruction is new but essential for oropharyngeal defects that result from robotic tumor excision. We report our experience with robotic free-flap reconstruction of head and neck defects to exemplify the necessity for robotic reconstruction. METHODS: We investigated head and neck cancer patients who underwent ablation surgery and free-flap reconstruction by robot. Between July 1, 2011 and March 31, 2012, 5 cases were performed and patient demographics, location of tumor, pathologic stage, reconstruction methods, flap size, recipient vessel, necessary pedicle length, and operation time were investigated. RESULTS: Among five free-flap reconstructions, four were radial forearm free flaps and one was an anterolateral thigh free-flap. Four flaps used the superior thyroid artery and one flap used a facial artery as the recipient vessel. The average pedicle length was 8.8 cm. Flap insetting and microanastomosis were achieved using a specially manufactured robotic instrument. The total operation time was 1,041.0 minutes (range, 814 to 1,132 minutes), and complications including flap necrosis, hematoma, and wound dehiscence did not occur. CONCLUSIONS: This study demonstrates the clinically applicable use of robots in oropharyngeal reconstruction, especially using a free flap. A robot can assist the operator in insetting the flap at a deep portion of the oropharynx without the need to perform a traditional mandibulotomy. Robot-assisted reconstruction may substitute for existing surgical methods and is accepted as the most up-to-date method.
Arteries ; Demography ; Forearm ; Free Tissue Flaps ; Glycosaminoglycans ; Head ; Head and Neck Neoplasms ; Hematoma ; Humans ; Neck ; Necrosis ; Oropharynx ; Robotics ; Thigh ; Thyroid Gland

BACKGROUND: The soft palate functions as a valve and helps generate the oral pressure required for normal speech resonance. Speech problems and nasal regurgitation can result from a soft palatal defect. Reduction of the size of the velopharyngeal orifice is required to compensate for the lack of mobility in a reconstructed soft palate. We suggest a large volume folded free flap for reduction of the caliber and a palmaris longus tendon sling for suspension of the reconstructed palate. METHODS: Six patients had total soft palate resection for tonsillar cancer and reconstruction with a large volume folded radial forearm free flap combined with a palmaris longus sling. A single surgeon and speech therapist examined the patients with three standardized speech assessment tools: nasometer test, consonant articulation test, and speech acuity test performed for speech evaluation. RESULTS: Mean nasalance score was 76.20% for sentences with nasal sounds and 43.60% for sentences with oral sounds. Hypernasality was seen for oral sound sentences. The mean score of the picture consonant articulation test was 84% (range, 63% to 100%). The mean score of the speech acuity test was 5.84 (range, 5 to 6). These mean ratings represent a satisfactory level of speech function. CONCLUSIONS: The large volume folded free flap with a palmaris longus tendon sling for total soft palate reconstruction resulted in satisfactory prognosis for speech despite moderate hypernasality.
Forearm ; Free Tissue Flaps ; Humans ; Palate, Soft ; Prognosis ; Tendons ; Tonsillar Neoplasms

BACKGROUND: The anterolateral thigh (ALT) perforator flap has become a popular option for treating soft tissue defects of lower extremity reconstruction and can be combined with a segment of the vastus lateralis muscle. We present a comparison of the use of the ALT fasciocutaneous (ALT-FC) and myocutaneous flaps. METHODS: We retrospectively reviewed patients in whom free-tissue transfer was performed between 2005 and 2011 for the reconstruction of lower extremity soft-tissue defects. Twenty-four patients were divided into two groups: reconstruction using an ALT-FC flap (12 cases) and reconstruction using a vastus lateralis myocutaneous (VL-MC) flap (12 cases). Postoperative complications, functional results, cosmetic results, and donor-site morbidities were studied. RESULTS: Complete flap survival was 100% in both groups. A flap complication was noted in one case (marginal dehiscence) of the ALT-FC group, and no complications were noted in the VL-MC group. In both groups, one case of partial skin graft loss occurred at the donor site, and debulking surgeries were needed for two cases. There were no significant differences in the mean scores for either functional or cosmetic outcomes in either group. CONCLUSIONS: The VL-MC flap is able to fill occasional dead space and has comparable survival rates to ALT-FC with minimal donor-site morbidity. Additionally, the VL-MC flap is easily elevated without myocutaneous perforator injury.
Cosmetics ; Free Tissue Flaps ; Humans ; Lower Extremity ; Muscles ; Perforator Flap ; Postoperative Complications ; Quadriceps Muscle ; Retrospective Studies ; Skin ; Survival Rate ; Thigh ; Tissue Donors ; Transplants

BACKGROUND: Coverage of defects of the pretibial area remains a challenge for surgeons. The difficulty comes from the limited mobility and availability of the overlying skin and soft tissue. We applied variable pedicled perforator flaps to overcome the disadvantages of local flaps and free flaps on the pretibial area. METHODS: Eight patients who had the defects in the anterior tibial area were enrolled. Retrospective data were obtained on patient demographics, cause, defect location, defect size, flap dimension, originating artery, pedicle length, pedicle rotation, complication, and postoperative result. The raw surface created following the flap elevation was covered with a split thickness skin graft. RESULTS: Posterior tibial artery-based perforator flaps were used in five cases and peroneal artery-based perforator flaps in three cases. The mean age was 54.3 and the mean period of follow-up was 6 months. The average size of the flaps was 63.8 cm2, with a range of 18 to 135 cm2. There were no major complications. No patients had any newly developed functional deficit of the lower leg. CONCLUSIONS: We suggest that pedicled perforator flaps can be an alternative treatment modality for covering pretibial defects as a simple, safe and versatile procedure.
Arteries ; Demography ; Follow-Up Studies ; Free Tissue Flaps ; Humans ; Leg ; Perforator Flap ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin ; Surgical Flaps

BACKGROUND: Cranial base defects are challenging to reconstruct without serious complications. Although free tissue transfer has been used widely and efficiently, it still has the limitation of requiring a long operation time along with the burden of microanastomosis and donor site morbidity. We propose using a reverse temporalis muscle flap and calvarial bone graft as an alternative option to a free flap for anterior cranial base reconstruction. METHODS: Between April 2009 and February 2012, cranial base reconstructions using an autologous calvarial split bone graft combined with a reverse temporalis muscle flap were performed in five patients. Medical records were retrospectively analyzed and postoperative computed tomography scans, magnetic resonance imaging, and angiography findings were examined to evaluate graft survival and flap viability. RESULTS: The mean follow-up period was 11.8 months and the mean operation time for reconstruction was 8.4+/-3.36 hours. The defects involved the anterior cranial base, including the orbital roof and the frontal and ethmoidal sinus. All reconstructions were successful. Viable flap vascularity and bone survival were observed. There were no serious complications except for acceptable donor site depressions, which were easily corrected with minor procedures. CONCLUSIONS: The reverse temporalis muscle flap could provide sufficient bulkiness to fill dead space and sufficient vascularity to endure infection. The calvarial bone graft provides a rigid framework, which is critical for maintaining the cranial base structure. Combined anterior cranial base reconstruction with a reverse temporalis muscle flap and calvarial bone graft could be a viable alternative to free tissue transfer.
Angiography ; Bone Transplantation ; Depression ; Follow-Up Studies ; Free Tissue Flaps ; Graft Survival ; Humans ; Magnetic Resonance Imaging ; Medical Records ; Muscles ; Orbit ; Retrospective Studies ; Skull Base ; Surgical Flaps ; Tissue Donors ; Transplants