Vascularized free fibula flap oral rehabilitation using tissue engineered mucosa: Report of 3 cases.

The aim of this report is to introduce the use of the dermal substitute Integra® in the context of free fibula flap prelamination for mandibular reconstruction. Three cases of mandibular reconstruction with prefabricated and Integra-prelaminated vascularized fibula flaps are reported in this article. The patients reported in this case series presented with the following tumours: an extensive cemento-ossyfying fibroma, a multicystic ameloblastoma and an extensive calcifying epithelial odontogenic tumour. Virtual three-dimensional (3D) planning and 3D-printed cutting guides were used for the mandibulectomies, the flap harvest and the positioning of the implants. The dermal substitute Integra was used for prelamination instead of skin grafts. Treatment of all 3 patients was performed in two stages; the first consisted of the fibula prefabrication (dental implant insertion) and prelamination, and the second consisted of tumor resection and reconstruction with the vascularized implant-bearing fibula flap. Integra was shown to be able to generate complete mucosa-like tissue over the fibula flaps and in the peri-implant areas. The patients have been followed up for 1, 3 and 7 years, respectively, with satisfactory prosthetic, functional and aesthetic results. None of the patients developed peri-implant disease. It was observed that prelamination with the dermal substitute Integra leads to development of mucosal lining with clinical features similar to oral mucosa. In this report of three cases, use of Integra as part of the prelamination and prefabrication process, instead of skin grafts, appears able to clinically generate mucosal lining with avoidance of skin grafts.

Internal jugular vein duplication: clinical significance for head and neck cancer ablative and reconstructive surgery.

We present the case of a 75-year-old patient with a T2N0Mo oral cancer, who underwent surgery for cancer ablation and reconstruction. Intraoperatively, a duplicate internal jugular vein (IJV) was identified. Both segments were preserved. The veins of the free radial forearm flap that was used to reconstruct the defect were anastomosed to tributaries of the anterior IJV segment. In this rare anatomical variation, the anterior segment of IJV lies medially/anteriorly to the sternocleidomastoid muscle which poses a risk of inadvertent injury during the early steps of the neck dissection (ND). The posterior segment is at risk of injury during developing levels II-III-IV of ND. It is important to preserve the anterior IJV segment as this receives all tributaries that can be used for end-to-end anastomosis for the free flap. Preoperative contrast computed tomography scan can aid in recognition of IJV duplication and help prepare the surgeon to adjust certain operative steps.

Management of the clinically N0 neck in early-stage oral squamous cell carcinoma (OSCC). An EACMFS position paper.

Metastasis of oral squamous cell carcinoma (OSCC) to the cervical lymph nodes has a significant impact on prognosis. Accurate staging of the neck is important in order to deliver appropriate treatment for locoregional control of the disease and for prognosis. The management of the neck in early, low volume disease (clinically T1/T2 oral cavity tumours) has long been debated. The risk of occult nodal involvement in cT1/T2 OSCC is estimated around 20-30%. We describe the natural evolutionary history of OSCC and its patterns of spread and metastasis to the local lymphatic basins. We discuss most published literature and studies on management of the clinically negative neck (cN0). Particular focus is given to prospective randomized trials comparing the outcomes of upfront elective neck dissection against the observational stance, and we summarize the results of the sentinel node biopsy studies. The paper discusses the significance of the primary tumour histological characteristics and specifically the tumour's depth of invasion (DOI) and its impact on predicting nodal metastasis. The DOI has been incorporated in the TNM staging highlighting its significance in aiding the treatment decision making and this is reflected in world-wide oncological guidelines. The critical analysis of all available literature amalgamates the existing evidence in early OSCC and provides recommendations in the management of the clinically N0 neck.

Distinct expression patterns of the transcription factor E2F-1 in relation to tumour growth parameters in common human carcinomas.

E2F-1 is a pivotal transcription factor that integrates signals from a variety of G1/S phase regulators and modulates diverse cellular functions, such as DNA synthesis, repair, mitosis, and apoptosis. Its role in cellular proliferation and apoptosis, as depicted from experimental models and limited reports in human malignancies, remains a matter of debate. Recently, in non-small cell lung cancer, it was observed that E2F-1 overexpression was associated with tumour growth, implying an 'oncogenic' effect. To clarify further the role of E2F-1 in carcinogenesis, the investigation was expanded in four of the most common human malignancies by examining its expression status and putative impact on tumour kinetics. These issues were addressed by immunohistochemical and molecular means in 52 breast carcinomas, 42 prostate adenocarcinomas, 58 colon adenocarcinomas, and 77 superficial bladder transitional cell carcinomas (TCCs). The following results were found: (i). in breast carcinomas, E2F-1 expression correlated with proliferation (p < 0.001) and growth index (p = 0.001); (ii). in prostate adenocarcinomas, absence of E2F-1 was noted, in contrast to its expression in normal and hyperplastic glands; (iii). in colon adenocarcinomas, E2F-1 expression was inversely related to growth index (p = 0.001), being expressed in lesions with increased apoptosis (p = 0.001) and low proliferation (p < 0.001); and (iv) in superficial TCCs, E2F-1 expression correlated with proliferation (p = 0.002). Taken together, these results suggest that E2F-1 has a growth-promoting effect in breast carcinomas and superficial TCC, whereas the opposite seems to be the case for colon and prostate cancer. To interpret the above findings, the status of the pRb and p53 tumour suppressor pathways, which are known to affect E2F-1 activity, was further investigated. The results suggest that the actions of E2F-1 are mainly dependent on the functionality of these pathways. Nevertheless, the data also imply that p53-independent pathways may play a nodal role in the function of E2F-1 in colon cancer.

Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1.

Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1, leads to overreplication and chromosomal instability (CIN) in lower eukaryotes and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung carcinomas, and investigated for putative relations with G(1)/S phase regulators, tumor kinetics, and ploidy. This is the first study of these fundamental licensing elements in primary human lung carcinomas. We herein demonstrate elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of neoplasms, respectively, whereas aberrant expression of hGeminin was observed in 49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048, respectively). Supportive of the observed link between E2F-1 and hCdt1, we provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian cells. Interestingly, hGeminin overexpression was statistically related to increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The significance of these results was underscored by the fact that the latter parameters were independent of p53 within the hCdt1-hCdc6 normally expressing cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6 overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung carcinomas.