Beyond the boundaries of compartmental hemiglossectomy: a proposal for an anatomically based classification of surgical approaches to advanced oral tongue squamous cell carcinoma.

INTRODUCTION: In the last decade, compartmental surgery (CTS) has been the surgical approach of choice for advanced tumors of the tongue and oral floor. METHODS: Advanced tumors (cT3-T4) oral tongue squamous cell carcinoma (OTSCC) may extend beyond the lingual septum and involve the contralateral hemitongue, developing along the intrinsic transverse muscle. The disease may then involve the genioglossus muscle and, more laterally, the hyoglossus muscle. RESULTS: The surgical approach to the contralateral tongue must be guided by anatomic and anatomopathological principles to achieve a safe oncological resection based on the principles of CTS. CONCLUSION: We propose a schematic classification of glossectomies that extend to the contralateral hemitongue based on the anatomy and pathways of tumor spread.

Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers.

The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2'deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy.

Tongue reconstruction with the gracilis myocutaneous free flap.

We describe our experience in tongue reconstruction using the transverse gracilis myocutaneous (TMG) free flap after major demolitive surgery for advanced cancer. This technique was used in 10 patients: seven underwent total glossectomy and three partial glossectomy. In eight patients we performed motor reinnervation attempting to maintain muscular trophism and gain long-term volumetric stability. The follow-up period ranged from 6 to 28 months. The overall flap survival was 100%. Nine out of 10 patients resumed oral intake. Our preliminary experience shows that this flap is a good reconstructive option for total glossectomy patients, whereas it is less suited for reconstruction of hemiglossectomy defects. Functional and objective evaluation of the tongue reconstructed with TMG free flap requires further and standardized evaluation.

Free Periosteal Flaps with Scaffold: An Overlooked Armamentarium for Maxillary and Mandibular Reconstruction.

INTRODUCTION: Head and neck bone reconstruction is a challenging surgical scenario. Although several strategies have been described in the literature, bone free flaps (BFFs) have become the preferred technique for large defects. Revascularized free periosteal flaps (FPFs) with support scaffold represents a possible alternative in compromised patient, BFF failure, or relapsing cancers as salvage treatment. However, only few clinical applications in head and neck are reported in literature. Purpose of the study was to systematically analyse the results of functional and oncologic maxillary and mandibular reconstruction with FPF with scaffold. MATERIALS AND METHODS: A comprehensive review of the dedicated literature was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, Cochrane Library, Embase, Researchgate and Google Scholar databases using relevant keywords, phrases and medical subject headings (MeSH) terms. An excursus on the most valuable FPF' harvesting sites was also carried out. RESULTS: A total of 7 studies with 55 patients were included. Overall, the majority of the patients (n = 54, 98.1%) underwent an FPF reconstruction of the mandibular site. The most used technique was the radial forearm FPF with autologous frozen bone as scaffold (n = 40, 72.7%). The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. CONCLUSIONS: Maxillary and mandibular reconstruction with FPF and scaffold is a possible alternative in patient unfit for complex BFF reconstruction and it should be considered as a valid alternative in the sequential salvage surgery for locally advanced cancer. Moreover, it opens future scenarios in head and neck reconstructive surgery, as a promising tool that can be modelled to tailor complex 3D defects, with less morbidities to the donor site.

Step-by-Step Cadaver Dissection and Surgical Technique for Compartmental Tongue and Floor of Mouth Resection.

BACKGROUND: The aim of oral cancer surgery is tumor removal within clear margins of healthy tissue: the latter definition in the literature, however, may vary between 1 and 2 cm, and should be intended in the three dimensions, which further complicates its precise measurement. Moreover, the biological behavior of tongue and floor of mouth cancer can be unpredictable and often eludes the previously mentioned safe surgical margins concept due to the complexity of tongue anatomy, the intricated arrangements of its intrinsic and extrinsic muscle fibers, and the presence of rich neurovascular and lymphatic networks within it. These structures may act as specific pathways of loco-regional tumor spread, allowing the neoplasm to escape beyond its visible macroscopic boundaries. Based on this concept, in the past two decades, compartmental surgery (CS) for treatment of oral tongue and floor of mouth cancer was proposed as an alternative to more traditional transoral resections. METHODS: The authors performed three anatomical dissections on fresh-frozen cadaver heads that were injected with red and blue-stained silicon. All procedures were documented by photographs taken with a professional reflex digital camera. RESULTS: One of these step-by-step cadaver dissections is herein reported, detailing the pivotal points of CS with the aim to share this procedure at benefit of the youngest surgeons. CONCLUSIONS: We herein present the CS step-by-step technique to highlight its potential in improving loco-regional control by checking all possible routes of tumor spread. Correct identification of the anatomical space between tumor and nodes (T-N tract), spatial relationships of extrinsic tongue muscles, as well as neurovascular bundles of the floor of mouth, are depicted to improve knowledge of this complex anatomical area.

Classification of GLOSSECTOMIES: Proposal for tongue cancer resections.

BACKGROUND: Surgery of tongue tumors includes different procedures ranging from mucosal resection to complex combined resection. Numerous terms have been used to describe such procedures, but there is no consensus between the terminology and the extent of resection. METHODS AND RESULTS: We searched the medical literature and found a lack of published information. We undertook to describe a new classification of surgical procedures for tongue tumor resection. We based it upon the surgical anatomy of the tongue and the spread of the cancer. We posited that there were five major types of glossectomy embracing all the methods of tongue cancer resection. This classification was reviewed and endorsed by an international team of experts. CONCLUSION: We propose a more precise classification than that currently in practice, thereby bringing clarity and consistency to the terminology, facilitating shared communication between surgeons, comparison between published research, and ultimately improving surgical practice and patient care.

The role of the T-N tract in advanced stage tongue cancer.

BACKGROUND: We investigated the role of the soft tissue tract between the primary tumor and the neck lymph nodes, the "T-N tract," in patients with tongue squamous cell carcinoma at an advanced stage. METHODS: We performed a compartmental tongue surgery in 233 patients. Cumulative incidence of relapses and overall survival curves were compared by T-N tract involvement. Multivariate Cox proportional hazards models were used to assess the independent role of T-N tract. RESULTS: At 4 years of follow-up, patients with disease in the T-N tract experienced a significantly more distant recurrence (40%) than did patients without T-N tract involvement (22%; P = .02). Multivariate Cox models indicate a significant almost triple risk of distant metastases (hazard ratio [HR], 2.70; 95% CI, 1.01-7.19; P = .05) and double risk of death (HR, 2.09; 95%CI, 1.13-3.85; P = .02) in patients with "T-N tract involvement." CONCLUSIONS: Our data show that the T-N tract plays an important role in prognosis and survival in patients with tongue cancer.

From wide excision to a compartmental approach in tongue tumors: what is going on?

PURPOSE OF REVIEW: Surgical approaches to tongue cancer have not changed substantially over the years. The literature proposes some indications for tumor excision even though type of intervention, resection margins, neck dissection, and 'en bloc' resection versus separate excision of tumor and lymph nodes do not seem to be standardized. The purpose of this review is to describe the evolution of surgical management of tongue carcinoma with particular attention to recent reports focusing on compartmental tongue surgery. RECENT FINDINGS: The current literature usually describes resection of tongue carcinoma within wide disease-free margins, ranging from 1.5 to 2 cm. In case of advanced-stage tumors, performing concomitant neck dissection is recommended; otherwise, a deferred neck dissection is indicated if depth of neoplastic infiltration exceeds 4 mm. In recent years, a new technical approach has been formulated based on anatomy of the tongue, thus, introducing the concept of an anatomy-based, function sparing, compartmental surgery. SUMMARY: Applying such a proposal to clinical practice aims at standardizing a surgical procedure that otherwise might be arbitrary. Compartmental surgery improves overall survival, does not seem to worsen functional outcomes of the residual tongue, and allows comparison of case studies.

Total glossectomy with preservation of the larynx: oncological and functional results.

Our aim was to analyse the overall and disease-free survival (DFS), time to recovery of oral feeding, and morbidity, in a consecutive series of patients who had total glossectomy with preservation of the larynx for advanced cancer of the tongue at the European institute of Oncology (Milan). From June 2002 to April 2011, 37 patients who were treated for advanced cancer of the tongue had total glossectomy, bilateral neck dissection, and preservation of the larynx. Various flaps were used for reconstruction. Overall and disease-free survival were assessed from the day of operation to the latest outpatient examination. Postoperative morbidity and rehabilitation of feeding were also assessed. Six patients had major complications, four of whom had a second operation for necrosis of the flap. Actuarial five-year overall survival (OS) and disease-free survival were 54% and 47%. Twenty-four patients (65%) were operated on as their first treatment, and had 79% five-year overall survival and 61% 5-year disease-free survival. Twenty-six patients were eventually able to feed orally postoperatively. Although this retrospective study include a limited number of patients, the results support the validity of total glossectomy as a safe procedure for advanced cancer of the tongue. Pretreated patient were previously treated with surgery, radiotherapy or chemoradiotherapy with curative purposes. Nevertheless, the long period required for recovery of oral feeding indicates that total glossectomy should be reserved for highly motivated patients.

Compartmental tongue surgery: Long term oncologic results in the treatment of tongue cancer.

Compartmental tongue surgery (CTS) is a surgical technique that removes the compartments (anatomo-functional units) containing the primary tumor, eliminating the disease and potential muscular, vascular, glandular and lymphatic pathways of spread and recurrence. Compartment boundaries are defined as each hemi-tongue bounded by the lingual septum, the stylohyoid ligament and muscle, and the mylohyoid muscle. In this non-randomized retrospective study we evaluated the oncologic efficacy of CTS in patients with squamous cell carcinoma (SCCA) of the tongue treated from 1995 to 2008. We evaluated 193 patients with primary, previously untreated cT2-4a, cN0, cN+, M0 SCCA with no contraindication to anesthesia and able to give informed consent. Fifty patients treated between October 1995 and July 1999 received standard surgery (resection margin >1cm); 143 patients treated between July 1999 and January 2008 received CTS. Study endpoints were: 5-year local disease-free, locoregional disease-free and overall survival. After 5years, local disease control was achieved in 88.4% of CTS patients (16.8% improvement on standard surgery); locoregional disease control in 83.5% (24.4% improvement) and overall survival was 70.7% (27.3% improvement). The markedly improved outcomes in CTS patients, compared to those treated by standard surgery, suggest CTS as an important new approach in the surgical management of tongue cancer.

Composite reconstruction in advanced cancer of the mouth floor: autogenous frozen-thawed mandibular bone and free flaps.

Mandibular symphyseal resection requires composite reconstructions, often with unsatisfactory morphofunctional results. Seven patients with advanced squamous cell carcinoma of the floor of the mouth underwent block resection with immediate reconstruction, using the removed mandible treated with liquid nitrogen and covered with a free forearm flap. In all cases, the resection was radical and no major postoperative complications occurred. Two patients died in 6 months for distant metastases and regional recurrence. In the other 5 patients, no local recurrence occurred at a mean follow-up of 52 months (36-70). Immediate cosmetic and functional results were good. Of the 5 patients, 4 had late complications requiring further surgery. This technique of bone reimplantation produces no donor site morbidity, perfect immediate morphological result, and is of low cost. The free forearm flap is effective in sealing the oral cavity, though further clinical and experimental studies are necessary to reduce late local complications.