Huang-Kai Kao

Free-Style Flaps: A Further Step Forward for Perforator Flap Surgery

Background: Technical advancements and increased experience with perforator flap techniques have allowed the harvest of flaps in a free-style manner. Methods: To perform free or local island pedicled flaps using the free-style concept, one requires mature skills in retrograde dissection of vascular pedicles and in using a hand-held Doppler device. To keep the technique safe, certain principles should be remembered and are detailed in this article. Results: The free-style flap concept provides unparalleled freedom when choosing local or distant soft tissues for reconstructing a defect. Conclusions: Potential pitfalls during free-style flap harvest can be avoided if the presented principles are adhered to. Newer imaging modalities may prove useful for assessing vessels supplying any cutaneous territory.

A Strategic Approach for Tongue Reconstruction to Achieve Predictable and Improved Functional and Aesthetic Outcomes

Background: Successful tongue reconstruction should restore swallowing, speech function, and cosmesis. The purpose of this prospective study was to evaluate the functional and aesthetic outcomes of tongue reconstruction using variable free flaps based on different tongue defects. Methods: One hundred four patients with a mean age of 49 ± 11 years underwent free tissue transfer following resection of T2 to T4 tongue cancers. The defects were classified prospectively into three groups: group A, hemiglossectomy defects (n = 42) reconstructed with 33 radial forearm flaps and nine anterolateral thigh perforator flaps; group B, subtotal glossectomy defects (n = 50) reconstructed with anterolateral thigh perforator (n = 44) or anterolateral thigh myocutaneous flaps (n = 6); and group C, total glossectomy defects (n = 12) reconstructed with 12 pentagonal anterolateral thigh myocutaneous flaps. Results: Two flaps failed, giving a success rate of 98.1 percent. Two patients developed partial flap loss. At a mean follow-up of 46.2 months, 33 patients were available for evaluation. Normal speech was found in 13 patients, intelligible speech was found in nine, and slurred speech was found in 11. Sixteen patients could eat a normal diet, eight could eat a soft diet, seven could eat a liquid diet, and two required tube feeding (p = 0.28). The cosmetic results were rated as excellent in 19, good in nine, and fair in five patients (p = 0.76). Conclusions: A strategic approach of variable flap selections based on different tongue defects may achieve predictably better functional and aesthetic outcomes. The innovative pentagonal anterolateral thigh myocutaneous flap for total tongue reconstruction creates a free neotongue tip with adequate volume, producing acceptable swallowing function and cosmesis.

Comparison of the Medial Sural Artery Perforator Flap with the Radial Forearm Flap for Head and Neck Reconstructions

Background: For a small to medium-sized defect in the head and neck region after cancer ablation, the free radial forearm flap is commonly used. More recently, the free medial sural artery perforator flap has been used as an alternative. The authors investigated the outcome and donor-site morbidity of the free radial forearm flap and the free medial sural artery perforator flap for head and neck reconstruction. Methods: Between July of 2004 and May of 2008, 47 patients (45 men and two women) underwent head and neck reconstruction, with a free radial forearm flap used in 29 cases and a free medial sural artery perforator flap used in 18 cases. Patient age ranged from 30 to 70 years (mean, 50.5 years). Results: The success rate of free radial forearm and free medial sural artery perforator flaps was 100.0 percent. There was no significant difference in flap harvest time (57.5 minutes versus 60 minutes), hospital stay (24.5 days versus 19.7 days), or overall recipient-site complication rate (20.7 percent versus 11.1 percent). The free medial sural artery perforator flap group had a better subjective functional and cosmetic outcome in the donor site than the free radial forearm flap group (two-sided Fishers exact test, p = 0.0002). Conclusions: The medial sural artery perforator flap is a good alternative for head and neck reconstruction of small defects. The medial sural artery perforator flap is advantageous with regard to less donor-site morbidity compared with the free radial forearm flap. The unfamiliarity of the pedicle anatomy of the medial sural artery perforator flap must be weighed against an easily harvested radial forearm flap.

Anatomical basis and versatile application of the free medial sural artery perforator flap for head and neck reconstruction.

BACKGROUND The medial sural artery perforator flap is a thin and pliable flap. This study investigated the perforator topography of the medial sural artery perforator flap and its clinical application in head and neck reconstruction. METHODS From January of 2005 to April of 2009, 29 patients with 29 medial gastrocnemius territories were evaluated. Among them, 26 patients underwent head and neck reconstruction using 26 medial sural artery perforator flaps. The number, location, and topographic patterns of the perforators were measured. RESULTS Flap sizes ranged from 8 x 4 cm to 12 x 14 cm. The mean pedicle length was 12.7 cm, the mean flap thickness was 4.8 mm, the mean number of total perforators was 2.7 +/- 1.5 (range, 1 to 5), and the mean number of sizable perforators was 1.6 +/- 0.7 (range, 1 to 3). The mean distance from the perforator perpendicular to the popliteal crease was 11.4 +/- 2.7 cm. No perforators were found less than 6 cm or more than 18 cm from the popliteal crease. Most sizable perforators (85.4 percent) entered the medial gastrocnemius muscle at a relative distance of one-fifth to one-third of the lower leg length measured from the popliteal crease. All flaps survived, with good functional and aesthetic outcomes, except for one failed case. CONCLUSION The medial sural artery perforator flap is a good alternative for head and neck reconstruction, with the advantages of thin and pliable skin, a long and reliable vascular pedicle, straightforward intramuscular dissection, the possibility of chimeric flap design, and minimal donor-site morbidity.

Two small flaps from one anterolateral thigh donor site for bilateral buccal mucosa reconstruction after release of submucous fibrosis and/or contracture

Oral submucous fibrosis causes health-related and social problems for affected patients. Free flap reconstruction has proved effective for maintaining mouth opening after release of fibrosis. Two independent free flaps from separate donor sites, such as bilateral forearm flaps or bilateral anterolateral thigh (ALT) flaps, were traditionally required for reconstruction. The former option sacrifices one of the two major arteries in the forearm. Both options are time consuming and required two donor sites. To eliminate these disadvantages, we developed a technical modification that allows harvesting of two independent flaps from one ALT thigh based on one descending branch of the lateral circumflex femoral artery (d-LCFA). Eighteen flaps from nine donor sites were harvested for post-release reconstruction of oral submucous fibrosis. Mean flap size was 4.1 x 7.5 cm, mean pedicle length was 7.6 cm, mean ischaemia time was 104 min and mean total operation time was 13 h and 19 min. All donor sites were closed primarily, with one exception. One flap failed and was replaced with a contralateral ALT flap. One patient developed a wound infection and another developed a seroma at the recipient site. Four flaps required secondary de-bulking in three patients. The improvement in mouth opening was evaluated by inter-incisor distance (IID): mean preoperative IID was 9.6mm (range: 0-20mm), mean follow-up time was 16.2 months (range: 10-33 months); mean postoperative IID was 23.8mm and mean improvement in IID was 15.3mm (range: 10-27 mm). In conclusion, two independent flaps can be harvested from d-LCFA of the same thigh, instead of from both thighs, to reconstruct bilateral buccal defects after release of submucous fibrosis and/or contracture.

Overexpression of activin A in oral squamous cell carcinoma: association with poor prognosis and tumor progression.

BackgroundBoth activin A, a member of transforming growth factor β superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the potential role of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma.MethodsFor activin A and follistatin, the expression of tissue samples from 92 patients was examined by immunohistochemical study, and the serum levels of blood samples from 111 patients and 91 healthy controls were measured by enzyme-linked immunosorbent assay.ResultsWe found that overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). In survival analyses, patients with oral squamous cell carcinoma, whose tumors overexpressed activin A, had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA-attenuated cell proliferation, migration, and invasiveness.ConclusionsThese findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients’ survival and may contribute to tumor progression and metastasis.

Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis

We examined the role of macrophage inflammatory protein (MIP)-3α on oral cavity squamous cell carcinoma (OSCC) and whether it was involved in modulating OSCC cell functions. The study population was comprised of 102 patients with OSCC. MIP-3α levels in tissues were examined by immunohistochemistry and quantitative real-time RT-PCR. Effects of MIP-3α on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference. We found that MIP-3α was overexpressed in OSCC tumor cells. MIP-3α expression was significantly higher in tumor cells vs. normal epithelial cells, as determined by both quantitative real-time RT-PCR and immunohistochemistry. Overexpression of MIP-3α was significantly correlated with positive pN status (P=0.036). Nevertheless, there were no correlations related to patient age, pT status, overall pathological stage, cell differentiation, or perineural invasion. The long-term disease-specific survival for patient subgroups stratified by the absence or presence of MIP-3α overexpression was 70.9% vs. 54.7% (P=0.041). Multivariate analysis indicated that MIP-3α overexpression had a significantly lower disease-specific survival (hazard ratio: 2.158; P=0.037). Additionally, in vitro suppression of MIP-3α expression in OECM-1 cells using specific interfering RNAs attenuated cell migration and invasiveness. These findings suggest that MIP-3α overexpression in OSCC is associated with a poorer prognosis for patient survival and contributes to tumor metastasis.

Reconstruction of the buccal mucosa following release for submucous fibrosis using two radial forearm flaps from a single donor site

BACKGROUND Oral submucous fibrosis is a collagen disorder affecting the submucosal layer and can severely limit mouth opening. The use of bilateral forearm flaps to fill buccal defects following trismus release has proven to be effective and reliable. However, it requires the sacrifice of radial arteries from both forearms. We have developed a technique that allows for the harvest of two independent flaps from a single forearm donor site. METHODS Two separate flaps are designed on the same radial artery and concomitant vein pedicle. The distal flap is marked in the standard fashion and the proximal skin paddle is designed in the middle third of the forearm, based on septocutaneous branches of the radial artery. The two flaps are elevated and subsequently divided into two independent free flaps. Between June 2004 and June 2007, a total of 16 flaps were harvested from eight donor sites for buccal mucosa defects following trismus release. Improvements in mouth opening and buccal pliancy were evaluated by comparing preoperative and postoperative inter-incisal distance (IID) and maximal mouth capacity. RESULTS All flaps survived completely, and all donor sites were closed primarily, except for one. The mean flap size was 6.6x2.6cm (range: 6x2.5cm-7x3cm), mean pedicle length was 5.7cm, mean ischaemia time was 46min and mean total operating time was 8h 45min. At an average of 19.8 months follow-up, the inter-incisal distance averaged 29.13mm, an increase of 20.88mm compared with the preoperative measurement. The maximal mouth capacity averaged 55.63cc, an increase of 9.38cc compared with the preoperative measurement. CONCLUSION Two independent small flaps can be harvested safely from one radial forearm donor site. This approach is a useful option for reconstruction of bilateral buccal defects, particularly following submucous fibrosis release. The donor-site morbidity is minimal and limited to one forearm.

Serum levels of chemokine (C-X-C motif) ligand 9 (CXCL9) are associated with tumor progression and treatment outcome in patients with oral cavity squamous cell carcinoma

OBJECTIVES The aim of this cohort study was to examine the role of chemokine (C-X-C motif) ligand 9 (CXCL9) on oral cavity squamous cell carcinoma (OSCC). METHODS Sera from 181 OSCC patients, 231 healthy individuals, and 50 OSCC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. Effects of CXCL9 on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference. RESULTS CXCL9 expression was significantly higher than for normal epithelium in the tissue samples. CXCL9 serum concentrations were also significantly higher in OSCC patients compared to those in healthy individuals. Serum CXCL9 levels were significantly higher in OSCC patients with higher pT status, pathological overall stages, tumor depths, and positive bone invasion (P = 0.033, 0.004, 0.041, and 0.002, respectively). Moreover, OSCC patients with higher CXCL9 levels (> 209 pg/mL, median level) before treatment had worse prognoses for overall survival and disease-specific survival (P = 0.0006 and 0.0009, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for overall survival and disease-free survival (P = 0.003 and 0.004, respectively). The in vitro suppression of CXCL9 expression in SCC25 cells using specific interfering RNAs attenuated cell proliferation, migration and invasiveness. CONCLUSIONS Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of OSCC tumors and serum level of this ligand may be useful as a prognostic indicator.

Low-molecular-mass secretome profiling identifies HMGA2 and MIF as prognostic biomarkers for oral cavity squamous cell carcinoma

The profiling of cancer cell secretomes is considered to be a good strategy for identifying cancer-related biomarkers, but few studies have focused on identifying low-molecular-mass (LMr) proteins (<15 kDa) in cancer cell secretomes. Here, we used tricine–SDS-gel-assisted fractionation and LC–MS/MS to systemically identify LMr proteins in the secretomes of five oral cavity squamous cell carcinoma (OSCC) cell lines. Cross-matching of these results with nine OSCC tissue transcriptome datasets allowed us to identify 33 LMr genes/proteins that were highly upregulated in OSCC tissues and secreted/released from OSCC cells. Immunohistochemistry and quantitative real-time PCR were used to verify the overexpression of two candidates, HMGA2 and MIF, in OSCC tissues. The overexpressions of both proteins were associated with cervical metastasis, perineural invasion, deeper tumor invasion, higher overall stage, and a poorer prognosis for post-treatment survival. Functional assays further revealed that both proteins promoted the migration and invasion of OSCC cell lines in vitro. Collectively, our data indicate that the tricine–SDS-gel/LC–MS/MS approach can be used to efficiently identify LMr proteins from OSCC cell secretomes, and suggest that HMGA2 and MIF could be potential tissue biomarkers for OSCC.