Extensive and complex defects of the head and neck involving multiple anatomical and functional subunits are a reconstructive challenge. The purpose of this study is to elucidate the reconstructive indications of the use of simultaneous double free flaps in head and neck oncological surgery. This is a retrospective review of 21 consecutive cases of head and neck malignancies treated surgically with resection and reconstruction with simultaneous use of double free flaps. Nineteen of 21 patients had T4 primary tumor stage. Eleven patients had prior history of radiotherapy or chemo-radiotherapy. Forty-two free flaps were used in these patients. The predominant combination was that of free fibula osteo-cutaneous flap with free anterolateral thigh (ALT) fascio-cutaneous flap. The indications of the simultaneous use of double free flaps can be broadly classified as: (a) large oro-mandibular bone and soft tissue defects (n = 13), (b) large oro-mandibular soft tissue defects (n = 4), (c) complex skull-base defects (n = 2), and (d) dynamic total tongue reconstruction (n = 2). Flap survival rate was 95%. Median follow-up period was 11 months. Twelve patients were alive and free of disease at the end of the follow-up. Eighteen of 19 patients with oro-mandibular and glossectomy defects were able to resume an oral diet within two months while one patient remained gastrostomy dependant till his death due to disease not related to cancer. This patient had a combination of free fibula flap with free ALT flap, for an extensive oro-mandibular defect. The associated large defect involving the tongue accounted for the swallowing difficulty. Simultaneous use of double free flap aided the reconstruction in certain large complex defects after head and neck oncologic resections. Such combination permits better complex multiaxial subunit reconstruction. An algorithm for choice of flap combination for the appropriate indications is proposed.

Cancer-associated fibroblasts (CAFs) demonstrate the characteristics of myofibroblast differentiation by often expressing the ultrastructure of alpha-smooth muscle actin (αSMA). However, heterogeneity among cancer-associated fibroblasts (CAFs), with respect to αSMA expression, has been demonstrated in several clinical studies of oral cancer. Like normal stem cells, stem-like cancer cells (SLCCs) are also regulated extrinsically by its microenvironment; therefore, we postulated that the heterogeneous oral-CAFs would differently regulate oral-SLCCs. Using transcriptomics, we clearly demonstrated that the gene expression differences between oral tumor-derived CAFs were indeed the molecular basis of heterogeneity. This also grouped these CAFs in two distinct clusters, which were named as C1 and C2. Interestingly, the oral-CAFs belonging to C1 or C2 clusters showed low or high αSMA-score, respectively. Our data with tumor tissues and in vitro co-culture experiments interestingly demonstrated a negative correlation between αSMA-score and cell proliferation, whereas, the frequency of oral-SLCCs was significantly positively correlated with αSMA-score. The oral-CAF-subtype with lower score for αSMA (C1-type CAFs) was more supportive for cell proliferation but suppressive for the self-renewal growth of oral-SLCCs. Further, we found the determining role of BMP4 in C1-type CAFs-mediated suppression of self-renewal of oral-SLCCs. Overall, we have discovered an unexplored interaction between CAFs with lower-αSMA expression and SLCCs in oral tumors and provided the first evidence about the involvement of CAF-expressed BMP4 in regulation of self-renewal of oral-SLCCs.

Background: The prognostic significance of various histopathologic lymph node-based biomarkers in oral squamous cell carcinoma (OSCC) needs further evaluation. Methods: Retrospective analysis of 212 OSCC patients with regional metastasis to determine the association of extranodal extension (ENE), extent of ENE, size of metastatic deposit, lymph node yield (LNY), lymph node ratio (LNR), and topography of involvement with survival outcomes. Results: The presence of ENE, larger nodal deposit, higher pN stage, lymph nodes in the lower levels, and patients who did not receive adjuvant treatment had poor disease-free survival (DFS). In addition, more positive nodes and high LNR showed worse overall survival (OS). ENE beyond 5 mm resulted in poorer outcomes. Larger sizes of metastatic deposit predisposed to ENE. Multivariate analyses showed only lower level of neck involvement to affect both DFS and OS. Conclusions: Lymph node metastasis to lower levels and other lymph node characteristics affect prognosis and must be considered in the evolution of staging systems for OSCC.

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