Search

This is the first study to investigate the impact of a second fibula flap or a soft tissue flap combined with bridging plate for a repeated segmental mandibulectomy reconstruction on flap outcomes in head and neck cancer patients. A retrospective comparative analysis (2007-2016) of 61 patients who underwent a second segmental mandibulectomy was performed. 20 patients underwent a fibula flap reconstruction whereas 41 had a soft tissue flap and plate reconstruction. No significant difference was seen in the operative time, total hospital stay, flap loss, re-exploration rates, plate exposure rate, or recipient site infection rate. On multivariate analysis, patients reconstructed with a soft tissue flap and bridging plate (odds ratio (OR) 3.997; 95% confidence interval (CI), 1.046-15.280, p = 0.043) and complications developed in previous surgery (OR 4.792; 95% CI, 1.120-20.493, p = 0.035) were shown to be independent predictors of a prolonged nasogastric tube dependence. The utilization of a soft tissue flap with plate is associated with comparative results of acute complication rate within 1 week, recipient site infection rate, and plate exposure rate to free fibula flaps alone. Free fibula flaps may result in a decreased risk for prolonged tube dependence compared to free soft tissue flap reconstructions.

Epidermal growth factor receptor (EGFR) and activin A are both overexpressed in oral cavity squamous cell carcinoma (OSCC). We evaluated their clinical correlation and activin A-mediated EGFR regulation in this study. Overexpression of both transcripts/proteins indicated a poorer prognosis in OSCC patients. Knockdown of endogenous INHBA repressed the expression of EGFR and inhibited activin A-mediated canonical Smads, noncanonical phosphorylation of AKT (ser473) (p-AKT ser473) and SP1. Inhibition of PI3K signaling via its inhibitor attenuated p-AKT ser473 and in turn reduced SP1 and EGFR expression in the presence of recombinant activin A (rActivin A) in OSCC cells, as revealed via a luciferase assay and western blotting. However, canonical Smad signaling repressed the EGFR promoter, as revealed by a luciferase assay. The transcription factor SP1, its coactivator CBP/p300, and Smad proteins were recruited to the EGFR proximal promoter following rActivin A treatment, as revealed by chromatin immunoprecipitation (ChIP). Smad2/3/4 dramatically outcompeted SP1 binding to the EGFR proximal promoter following mithramycin A treatment. Activin A activates the PI3K and Smad pathways to compete for binding to overlapping SP1 consensus sequences on the EGFR proximal promoter. Nevertheless, canonical p-Smad2 was largely repressed in OSCC tumor tissues, suggesting that the activin A-mediated noncanonical pathway is essential for the carcinogenesis of OSCC.

Increasing evidence indicates that inflammation plays a crucial role in cancer development. A novel scoring system based on albumin and the neutrophil-to-lymphocyte ratio (NLR) was developed and incorporated into a nomogram to create a more accurate prognostic tool for oral cavity squamous cell carcinoma (OSCC) patients. A retrospective review was performed on 613 consecutive patients undergoing ablative surgery for OSCC between September 2005 and December 2014. NLR and albumin were determined and used to calculate an albumin/NLR score (ANS). The nomogram was based on the ANS and several clinicopathological manifestations, and its accuracy was determined by the concordance index (c-index). A high ANS was significantly associated with aggressive tumor behaviors, such as T status, overall stage, extranodal extension, perineural invasion, tumor depth, and decreased overall survival (OS). Multivariate analysis indicated that age, overall stage, extranodal extension, and ANS were independent factors for OS. The c-index for OS prognosis was 0.750 using this nomogram compared to 0.688 using TNM staging alone. The prognostic accuracy for OS in OSCC patients can be significantly improved using a nomogram that incorporates the novel ANS and other clinicopathological variables.

Performing a sequential third free flap for reconstruction of a head and neck defect after cancer resection can be challenging, and the problem is further compounded in elderly patients. The outcomes in this clinical scenario are currently unknown and this study aims to compare the results in elderly patients with younger patients in a high-volume microsurgical unit. A retrospective review of 126 consecutive patients who had undergone three sequential free flap reconstructions after head and neck cancer was performed. The patients were divided into two groups - older or younger than 65 years old (n = 105 and n = 21, respectively). Patient demographics, intraoperative and postoperative outcomes were noted and analyzed. The overall flap success in this patient cohort was 94.4% (7 flap losses in 126 patients). Cardiovascular complications were significantly more common in the older group (19% vs. 1.9%, p = 0.001). Delirium occurred more frequently in the older group compared with the younger group (23.8% vs. 6.7%, p = 0.023). There were no significant differences regarding surgical complications. With adequate planning, a sequential third free flap can be performed safely and successfully in patients who are more than 65 years of age. Particular attention to the perioperative morbidity in elderly patients is crucial for successful outcomes.

Despite increasing application of the pre-grafting expansion during autologous fat transplantation in breast reconstruction, little is known about its mechanism of action. To address that, ventral skins of miniature pigs were treated over a 10-day or 21-day period, with continuous suction at -50 mm Hg via a 7-cm diameter rubber-lined suction-cup device. Soft tissue thickness increased immediately after this external volume expansion (EVE) treatment, such increase completely disappeared by the next day. In the dermis and subcutaneous fat, the EVE treated groups showed significant increases in blood vessel density evident by CD31 staining as well as in vascular networks layered with smooth muscle cells when compared with the control group. This finding was corroborated by the increased percentage of endothelial cells present in the treatment groups. There was no significant difference in the percentages of proliferating basal keratinocytes or adipocytes, nor in epidermal thickness. Moreover, the EVE had no effect on proliferation or differentiation potential of adipose stem cells. Taken together, the major effects of EVE appeared to be vascular remodeling and maturation of functional blood vessels. This understanding may help clinicians optimize the vascularity of the recipient bed to further improve fat graft survival.

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.

Due to the significant morbidity and mortality associated with pharyngocutaneous fistula in pharyngoesophageal reconstruction following cancer resection, the purpose of this retrospective study is to examine the selection of tubed skin flaps that impact anastomotic integrity. The flaps evaluated included radial forearm flap versus anterolateral thigh flap, and fasciocutaneous anterolateral thigh flap versus chimeric anterolateral thigh flap. The outcome of interest is the incidence of pharyngocutaneous fistula. The radial forearm group had a significantly higher rate of fistula than the anterolateral thigh group (56.6% vs. 30.2%, p = 0.03). No significant difference in the incidence of fistula was demonstrated between fasciocutaneous and chimeric anterolateral thigh flap (36.8% vs. 25%, p = 0.51). The anastomotic integrity in pharyngoesopharyngeal reconstruction is affected by choice of skin flaps. Anterolateral thigh flap appears to be a viable option for pharyngoesophageal reconstruction. The more technical demand of the anterolateral thigh flap must be weighed against an easily harvested radial forearm flap.