Prognostic impact of marginal mandibulectomy in the presence of superficial bone invasion and the nononcologic outcome

Chen, Yih-Long; Kuo, Shih-Wei; Fang, Ku‐Hao; Hao, Sheng‐Po

doi:10.1002/hed.21530

Cited by 37 publications

(25 citation statements)

References 20 publications

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“…Lesions occurring in the retromolar trigone, gingiva, hard palate, buccal mucosa extending to sulci or tongue extending to floor of mouth may involve bone of the maxilla and/or the mandible. The prevalence of mandibular bone involvement by OSCC is reported to range from 12% to 56% of cases [4][5][6]. Such patients commonly have severe dysfunction of speech, mastication and/or swallowing.…”

Section: Introductionmentioning

confidence: 97%

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Quan

Johnson

Zhou

et al. 2011

Cancer Metastasis Rev

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Bone invasion is a common characteristic of oral squamous cell carcinoma (OSCC), with adverse affects on patient functionality and survival. Recent studies suggest that it is osteoclasts, rather than malignant keratinocytes themselves, which play the major role in facilitating the entry of the tumour into bone, and its progression within bone. Osteoclasts respond to a variety of local signalling pathways, initiated by products of the malignant epithelial cells. In the present review, we firstly introduce the clinical patterns of bone invasion, and then summarise these signalling pathways and their diverse roles in sequential phases of bone invasion. We also review current researches regarding the incidence and mechanisms of distant metastases to bone, and explain briefly the concept of epithelial-mesenchymal transition, which may generate cancer stem cells and initiate the bone invasion. Finally, we discuss more briefly approaches to the diagnosis and management of OSCC patients with bone invasion. With all these studies and some recent discoveries in our own laboratory, an enhanced understanding of bone invasion will be achieved, which should indicate potential molecular targets for future biotherapies.

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Section: Introductionmentioning

confidence: 97%

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Quan

Johnson

Zhou

et al. 2011

Cancer Metastasis Rev

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“…The incidence is as high as 56 % of investigated patients [1, 2]. Bone involvement contributes to increased morbidity, higher recurrence and mortality rates [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

Quan

Elhousiny

Johnson

et al. 2013

Clin Exp Metastasis

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This study investigates relationships between EMT and bone invasion by OSCC. Three OSCC cell lines, SCC25, HN5, and Tca8113 were artificially induced to display EMT by adding 5 ng/mL of TGF-β1 to culture media for 1–3 days. Cell morphology and phenotypic changes was examined by immunocytochemical staining of CK and VIM. EMT markers, cell-invasion factors, and osteoclast-related molecules were analysed at mRNA, gelatine and protein levels by real-time PCR, gelatine zymography and Western blotting respectively. Mature osteoclasts differentiated from Raw264.7 cells were treated by conditioned medium (CM) of OSCC cells with/without TGF-β1. Immunohistochemistry was performed to validate proteins of CK, VIM, E-cad and Snail1 in OSCC tissue samples with bone invasion. Results showed minimal staining of VIM was found in SCC25 and HN5, while Tca8113 cells stained strongly. EMT markers Twist1 and N-cad were up-regulated; Snail1 and E-cad down-regulated in all cells. Of factors associated with invasion, MMP-2 was unchanged and MMP-9 increased in SCC25 and Tca8113, while MMP-2 was increased and MMP-9 unchanged in HN5. For osteoclast-related molecules, both MT1-MMP and RANKL were up-regulated, while OPG was down-regulated in all cells. CM of OSCC cells pre-treated with TGF-β1 showed to prolong survival of osteoclasts up to 4 days. All target molecules were validated in OSCC samples of bone invasion. These findings suggest that TGF-β1 not only induces EMT to increase the capacity of OSCC for invasion, but also promotes factors which prolong osteoclast survival. TGF-β1 may enhance the ability of MMP2/9 in resorbing bone and favouring invasion of cancer cells.

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“…Over the past 40 years, marginal mandibulectomy has been considered for patients with oral cavity cancer that either approached or superficially eroded the mandible in order to maintain the continuity and preservation of jaw function . Mandibulotomy, on the other hand, is a surgical approach that improves access to deeper tumors in the oral cavity .…”

Section: Discussionmentioning

confidence: 99%

A nomogram to predict osteoradionecrosis in oral cancer after marginal mandibulectomy and radiotherapy

et al. 2019

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Objective: There is no useful tool to clinically predict the occurrence of osteoradionecrosis (ORN) of the mandible quantitatively. The aim was to investigate the risk factors, including different modalities of radiotherapy, for developing mandibular ORN in patients undergoing marginal mandibulectomy and postoperative radiotherapy.Methods: Between January 2006 and December 2012, 167 subjects who underwent marginal mandibulectomy and postoperative radiotherapy with different modalities were enrolled. The association of ORN with mandibular bone measurements and patient variables was analyzed, and a nomogram was established.Results: Fifteen (8.98%) of the 167 patients developed ORN during the follow-up period, and ORN was significantly associated with diabetes mellitus (DM), body mass index (BMI), remaining bone height, remaining bone height to original bone height ratio, resected bone height to original bone height ratio, and mandibular dose (P: < 0.001, 0.004, 0.042, 0.018, 0.010, 0.020, respectively). Interestingly, the risk of ORN had no significant difference between conformal and intensity modulation radiation therapy (P = 0.407). Multivariate analysis revealed that DM and resected bone height to original bone height ratio ≥ 50% were independent risk factors for postoperative ORN. A nomogram consisting of BMI, DM, resected bone height to original bone height ratio, mandibulotomy, and mandibular dose for predicting the ORN-free probability was established; and the c-index of the nomogram for ORN status was 0.803.Conclusion: A nomogram based on the risk factors was plotted to strengthen the prediction of ORN quantitatively. Surgeons should be more discrete regarding the treatment plan for patients with higher probability of ORN.

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Prognostic impact of marginal mandibulectomy in the presence of superficial bone invasion and the nononcologic outcome

Abstract: Marginal mandibulectomy is oncologically sound in providing a safe resection margin in oral cavity cancer abutting or superficially invading the mandible.

Cited by 37 publications

References 20 publications

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Transforming growth factor-β1 treatment of oral cancer induces epithelial-mesenchymal transition and promotes bone invasion via enhanced activity of osteoclasts

A nomogram to predict osteoradionecrosis in oral cancer after marginal mandibulectomy and radiotherapy

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