Do predetermined surgical margins compromise oncological safety in computer-assisted head and neck reconstruction?

OBJECTIVES: Computer assisted head and neck reconstruction has gained popularity over the past few years. In computer assisted surgery (CAS), surgical margins are predetermined in virtual surgery and resection guides are designed to be fitted intra-operatively. However, concerns have been raised regarding the oncological safety of predetermined surgical margins. Therefore, the aim of this study was to compare surgical margins, recurrence and survival outcomes in patients underwent CAS and non-CAS in head and neck reconstruction. METHODS: We retrospectively reviewed the patients underwent oral and maxillofacial malignancies surgical excision and free flap reconstruction from October 2014 to December 2019 by the same chief surgeon. Patients were divided into two groups depending on whether CAS and predetermined surgical margins were adopted. The primary outcome was surgical resection margin and the secondary outcomes included recurrence and survival. RESULTS: A total of 66 subjects were recruited with 37 in the CAS group and 29 in the non-CAS group. The follow-up rate was 100%. The average follow-up time was 24.5 months. No significant difference in resection margin was identified between the groups (p = 0.387). Tumor staging, margin status, perineural invasion, lymphovascular invasion and extranodal extension were identified as significant factors influencing survival. Both before and after adjustment for these prognostic factors identified, CAS and non-CAS group showed no significant difference in survival outcome. CONCLUSION: Predetermined surgical margins do not compromise oncological safety in terms of resection margin, disease recurrence and patient survival.

Ameloblastic carcinoma: Clinicopathological analysis of 18 cases and a systematic review.

OBJECTIVES: Exploring the clinicopathological features of ameloblastic carcinoma (AC) and reviewing the literature to improve the diagnosis and treatment of the disease. MATERIALS AND METHODS: Clinical data and pathological features of 18 cases of AC were retrospectively analyzed. A systematic review was carried out by searching PubMed and Medline databases using the MeSH terms "ameloblastic" and "carcinoma." RESULTS: In the systematic analysis, 125 cases of AC from 81 eligible original studies and 18 cases of AC from this research were included. The male-to-female ratio was 2.58:1, and the mandible-to-maxilla ratio was 1.80:1. Mean age of patients was 45.3 years. Thirty-seven cases of recurrence and 27 cases of metastasis were recorded. CONCLUSION: AC is a rare neoplasm of the odontogenic epithelium. A systematic review indicates that diagnoses at the early phase and a close periodic assessment for recurrence and metastasis are necessary.

Definitive radiotherapy vs. postoperative radiotherapy for lower gingival carcinomas of the mandible : A single-center report about outcome and toxicity.

PURPOSE: To assess radiotherapy (RT) outcomes in patients with gingival carcinoma and growth up to or involvement of the lower jaw bone. METHODS: This was a retrospective analysis of 51 patients with squamous cell carcinomas of the gingiva. Patients received definitive (group 1, 31.4%) or postoperative (group 2, 66.7%) RT between 2005 and 2017 at the Department of Radiation Oncology, University Hospital Heidelberg. The primary endpoint was overall survival (OS) in both treatment groups. Other endpoints were local-disease-free survival (LDFS), progression-free survival (PFS) and treatment-related toxicity (Common Terminology Criteria for Adverse Events, CTCAE, Version 4.03). RESULTS: Median age at first diagnosis was 63 years. All patients had a local advanced disease (American Joint Commission on Cancer [AJCC] stage III-IV). After a median follow-up of 22 months (range 3-145 months), 20 patients (39.2%) were still alive. At 5 years, OS rate was 36.6%. No significant differences in OS (p = 0.773), PFS (p = 0.350) and LDFS (p = 0.399) were observed between the two groups. Most common higher-grade acute RT-related complications (≥ grade 3) were dermatitis (78.2%), oral mucositis (61.7%), xerostomia (51.5%), and loss of taste (74.6%). Three cases (5.8%) of osteoradionecrosis (ORN) of the lower jaw were detected after 15-31 months. CONCLUSIONS: Definitive and postoperative RT have similar treatment outcomes for patients with lower gingiva carcinomas of the lower jaw. The most common acute complications (grade ≥3) were dermatitis, oral mucositis, xerostomia and loss of taste.

Sarcomas of the mandible.

INTRODUCTION: Sarcomas of the mandible are extremely rare tumors, with osteosarcoma being the most common, followed by Ewing's sarcoma MATERIALS AND METHODS: A retrospective review of the clinical records, imaging studies, and pathology slides of patients with sarcoma of the mandible at a Tertiary Care Cancer Center from 1998 to 2014 was undertaken. The impact of neoadjuvant chemotherapy and postoperative radiotherapy with or without chemotherapy was studied, and factors impacting upon local control and disease-specific survival were analyzed. RESULTS: Twenty-two patients were treated over the study period, comprising of 15 males and seven females. External swelling, intraoral growth, or facial numbness were the presenting symptoms. Eighteen patients had osteosarcoma and four had the Ewing's sarcoma. Nine patients received neoadjuvant chemotherapy. All but one patient underwent surgery. Eleven had negative margins, with 90% recurrence-free survival at 3 years, compared to 10 with positive or close margins, leading to 67% recurrence-free survival. None of the patients receiving neoadjuvant chemotherapy developed recurrence and all were alive at 3 years. The impact of postoperative radiotherapy or adjuvant chemotherapy was not statistically significant. CONCLUSIONS: Wide surgical resection with negative margins remains the hallmark of surgical treatment.

Survival Outcomes in T4aN0M0 Mandibular Gingival Squamous Cell Carcinoma Treated with Surgery Alone.

OBJECTIVES: To measure disease-free, disease-specific, and overall survival among patients with T4aN0M0 mandibular gingival squamous cell carcinoma who were treated with surgery alone. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: A retrospective chart review was performed of all adult patients treated surgically with an oral cavity composite resection between January 2005 and March 2017. Among other data, patient preoperative characteristics were recorded (eg, age, sex, smoking history, alcohol use, and clinical stage); operative notes were reviewed to determine tumor subsite involvement, reconstruction method, and intraoperative surgical complications; and pathology reports were evaluated for various pathologic findings. Survival outcomes were determined with Kaplan-Meier analysis. RESULTS: The mean follow-up was 18.5 months (range, 0.1-100). The 1- and 5-year disease-free survival rates were 90.5% and 84.5%, respectively, while the 1- and 5-year disease-specific survival rates were 87.8% and 81.9%. The 1- and 5-year overall survival rates were 86.4% and 80.6%. CONCLUSIONS: Patients with T4aN0M0 squamous cell carcinoma of the mandibular gingiva treated with surgery alone have a 5-year overall survival of 80.6%. Treatment with surgery alone obviates morbidities associated with adjuvant therapy while upholding survival outcomes.

Mandibular Invasion by Oral Squamous Cell Carcinoma: Clinicopathologic Features of 74 Cases.

OBJECTIVES: (1) For patients with oral squamous cell carcinoma (OSCC) and mandibular invasion, to determine whether prior radiation to the head and neck region (PXRTHN) affects the density of osteoblasts, osteoclasts, or fibroblasts along the tumor interface invading the mandible and whether this is significantly associated with overall survival. (2) To identify clinicopathologic features that are associated with overall survival. STUDY DESIGN: Case series with chart review. SETTING: University of Missouri hospital. SUBJECTS AND METHODS: Retrospective review of 74 cases with pathologically confirmed mandible invasion by OSCC and surgical treatment between January 1, 2005, and December 31, 2015. A board-certified anatomic pathologist reviewed the slides from all mandibulectomy cases. RESULTS: The mean density of osteoclasts was 2.0 per linear mm among the patients with PXRTHN and 7.1 among those without PXRTHN ( P < .001). Positive soft tissue frozen section margin was significantly associated with overall survival on univariate analysis ( P < .001; hazard ratio [HR], 0.34; 95% CI, 0.19-0.62) and multivariate analysis ( P = .026; HR, 0.41; 95% CI, 0.19-0.90). Maximum tumor dimension was significantly associated with overall survival on univariate analysis ( P = .021; HR, 1.19; 95% CI, 1.03-1.38) and multivariate analysis ( P = .002; HR, 1.49; 95% CI, 1.16-1.93). Osteoclast, osteoblast, and fibroblast density were not associated with overall survival. CONCLUSIONS: (1) Osteoclast density along the tumor front is significantly lower among patients with PXRTHN. Stromal cell density was not associated with overall survival. (2) Positive soft tissue frozen section margin and maximum tumor dimension are significantly associated with overall survival among patients with mandibular invasion by OSCC.

p16 protein expression and correlation with clinical and pathological features in osteosarcoma of the jaws: Experience of 37 cases.

BACKGROUND: In literature, no markers have been reported as predictive and prognostic factors in osteosarcoma of the jaw. METHODS: A retrospective analysis of p16 expression was performed in 37 patients with high-grade osteosarcoma of the jaw to investigate its potential prognostic and predictive value. RESULTS: p16 positivity was found in 56.7% of cases. The absence of p16 expression was associated with an adverse disease-free survival (P = .003). At the multivariate Cox regression, positive margins were the only independent factor. In the subgroup of 17 patients who underwent neoadjuvant chemotherapy, a significant association was noted between p16 expression and pathological response to chemotherapy (P = .015) and the negativity of p16 increased the risk of negative outcome (P = .01). CONCLUSION: Our data indicate that the wide surgical margin is the most important prognostic factor. The expression of p16 confers greater sensitivity to chemotherapy and its loss of expression is associated with a worse prognosis.

Osteosarcoma of the Mandible: A Site-Specific Study on Survival and Prognostic Factors.

Osteosarcoma of head and neck is a rare condition comprising of <1% of all head and neck cancers, retrospective studies show difference in survival of mandibular osteosarcoma to other head and neck sites, necessitating investigation into site-specific survival and recurrence rates.

Endoscope-Assisted Enucleation of Mandibular Odontogenic Keratocyst Tumors.

The keratocyst odontogenic tumor (KCOT) represents a rare and benign but locally aggressive developmental cystic lesion usually affecting the posterior aspect of the mandible bone, the treatment of which has always been raising debate, since Philipsen first described it as a distinct pathological entity in 1956.Recent studies have proposed the use of endoscope-assisted surgical technique, due to the possibility given by the endoscope of improving the effectiveness of the treatment of these lesions thanks to a better visualization of operative field and though a better understanding of the pathology. In this article, we would like to present our experience with the endoscope-assisted treatment of KCOT of the posterior region of the mandible.From April 2000 to April 2012, 32 patients treated for KCOT were enrolled in our retrospective study: patients were divided in 2 groups according to the type of treatment, that is, 18 were treated with traditional enucleation surgery (TES), and 14 patients underwent endoscopic assisted enucleation surgery (EES).Fischer exact test and Kaplan-Meier curves were used to compare the outcomes between the 2 focusing on the recurrence and complication rates. In the TES group, patients we found a higher recurrence rate (39%) and higher postoperative complication rate at 5-year follow-up.Our data suggested, though, that EES seems to be a feasible alternative for the treatment of posterior mandibular KCOT. Further studies and larger series are needed to confirm these results.

Clinicopathological Study of Primary Intraosseous Squamous Cell Carcinoma of the Jaw and a Review of the Literature.

PURPOSE: Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant odontogenic tumor that originates from odontogenic epithelial remnants. It is often difficult to diagnose PIOSCC definitively; hence, extraction or surgical treatment is performed before the initial diagnosis in most cases. The present study examined new insights into and prognostic factors of patients with PIOSCC admitted to the authors' department. MATERIALS AND METHODS: An extensive record review was conducted of patients who underwent radical surgery for PIOSCC from January 2001 through December 2014. RESULTS: Of all cases of OSCC, the frequency of PIOSCC was 1.45%. The 2-year relapse-free survival (RFS) and overall survival (OS) rates were 50.0 and 41.6% in all cases, respectively. Three patients underwent surgery or tooth extraction before the initial diagnosis; in fact, intervention before initial diagnosis was found to be an important poor prognostic factor for RFS and OS. In contrast, patients who were not treated before the initial diagnosis was made did not exhibit any locoregional recurrence. CONCLUSIONS: The treatment of PIOSCC should be similar to that for oral cancer with at least clinical stage T3N0 in the National Comprehensive Cancer Network clinical practice guidelines. In addition, cases of PIOSCC that are not treated before the initial diagnosis are more likely to obtain a good prognosis.

Local therapy in non-metastatic primary Ewing sarcoma of the mandible and maxilla in children.

Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all sites. Due to their rarity, a specific policy for local treatment is lacking. The aim of this study was to evaluate the local therapy for ES and recommend measures to individualize treatment options. Patients with primary non-metastatic ES of the jaw bones treated between August 2005 and February 2015 were analyzed. All patients received primary induction chemotherapy, following which lesions amenable to resection based on specific radiological criteria were resected; those with unresectable lesions were offered definitive radiotherapy. The maxilla was the primary site in 13 patients and the mandible in eight. The median age of patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17 patients and definitive radiotherapy was used in four patients. Postoperative radiotherapy was administered to 12 patients and was avoided in five patients with 100% tumour necrosis. The 3-year overall survival, event-free survival, and local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a histological response to chemotherapy were significant prognostic factors. The stratification of patients based on radiological criteria aids in selecting local therapy. In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcomes. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Pediatric maxillary and mandibular tumors.

Pediatric maxillary and mandibular tumors offer considerable challenges to otolaryngologists, oral surgeons, pathologists, and radiologists alike. Because of the close proximity to vital structures, appropriate steps toward a definitive diagnosis and treatment plan are of paramount importance. This article reviews the most common causes of pediatric jaw masses and discusses diagnostic and therapeutic considerations and recommendations.

Primary non-metastatic Ewing sarcoma of the jaw in children: results of surgical resection and primary reconstruction.

BACKGROUND AND OBJECTIVE: The rarity of Ewing sarcoma (ES) of the jaw coupled with the technical challenge of resection and associated functional and cosmetic impairment has resulted in deficient data on surgical management of these tumors. The purpose of this study is to describe the results of surgical excision and reconstruction of primary non-metastatic ES of the mandible and maxilla in children. METHODS: Consecutive patients (mandible = 6, maxilla = 5) treated with surgery from August 2005 to January 2013 were selected. All patients received induction chemotherapy and were selected for surgical resection based on the presence of specific criteria for operability. RESULTS: The median age was 11.5 years (range 5-16 years). Free fibular osteocutaneous flap was commonly used for reconstruction. There were no complications related to microvascular anastomosis or flap loss. Five patients had 100% tumor necrosis and did not receive radiotherapy. Teeth alignment, chewing, swallowing, and speech were normal in all and donor site morbidity occurred in one. The 5-year overall, event-free survival, and local control are 87.5%, 72.9%, and 90%, respectively. CONCLUSION: In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcome. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Changing indications for maxillomandibular reconstruction with osseous free flaps: a 17-year experience with 620 consecutive cases at UCLA and the impact of osteoradionecrosis.

OBJECTIVES/HYPOTHESIS: To characterize the changing indications for osseous free flaps in maxillomandibular reconstruction at our institution. STUDY DESIGN: Retrospective chart review. METHODS: Database review of patients who underwent free-flap reconstruction of the jaws using vascularized bone-containing free tissue transfer from 1995 to 2012 at the University of California Los Angeles (UCLA). RESULTS: A total of 620 osseous free flaps were performed. The most common indications for surgery were squamous cell carcinoma (n = 442) and osteoradionecrosis (ORN)) of the mandible (n = 73). There were no significant differences in 90-day perioperative complication, flap viability, or mortality rates between any of the indications for surgery. Patients older than 60 years had a higher rate of major perioperative complication (P = 0.0028). ORN cases represented 1.3% ± 1.2% of surgical volume from 1995 to 2000, 8.7% ± 1.8% from 2001 to 2006, and 17.5% ± 2.2% from 2007 to 2012 (P <0.0001). Among cases of ORN, 95.8% of patients had radiation therapy completed at centers outside of our hospital system. For patients with ORN, there was an average interval of 8.7 ± 8.0 years from initiation of radiotherapy to the date of mandibulectomy (range 1-37 years). CONCLUSION: The incidence of ORN as an indication for free-flap reconstruction has increased at our institution in recent years. This may reflect an increasing need for the surgical management of medically refractory ORN, a rising awareness or prevalence of ORN overall, and/or increasing comfort with free flaps as a treatment for ORN. Patients who undergo free-flap surgery for ORN do not have greater risks of 90-day perioperative complications or differences in free-flap viability as compared to patients who undergo free-flap reconstruction for other indications. LEVEL OF EVIDENCE: 2b.

Mandible bone metastases secondary to pulmonary adenocarcinoma.

OBJECTIVE: Metastatic tumors of the mandible are rare and usually present clinically as growths. The prognosis of lung cancer patients with bone metastases is poor. CASE REPORT: This article shows a metastasis from adenocarcinoma of the lung affecting the mandible of a 75-year-old female patient where the metastatic lesion was detected before primary tumor. The patient were treated with radiation therapy with palliative and antalgic intent. But the patient died 8 weeks after the diagnosis. CONCLUSION: Radiation therapy was effective and well tolerated in the case. Bone metastases particularly mandible metastasis of lung cancer has poor prognosis. Palliative and supportive therapy may be firstly chose because of poor prognosis.

Alloplastic mandibular reconstruction: a systematic review and meta-analysis of the current century case series.

BACKGROUND: Alloplastic mandibular reconstruction remains insufficiently predictable, with no systematic reviews to assess its scope and limitations. METHODS: The PubMed, CINAHL, EMBASE, and Web of Science databases were searched for English study reports, published in the current century, of mere alloplastic surgical reconstruction of mandibular ablative defects. RESULTS: In 14 articles, there were 944 patients, with a median age of 58.7 years (interquartile range, 53.2 to 62 years); 58.7 percent (interquartile range, 66.7 to 78.6 percent) were male. Cases of squamous cell carcinoma per study constituted 93.5 percent (interquartile range, 81.5 to 100 percent). Defects were mostly lateral (Boyd classification) (60.5 percent; interquartile range, 56.2 to 62 percent) and received mostly conventional bridging plates (in 64.3 percent of the studies) and pedicled flaps (45.3 percent; interquartile range, 37.1 to 58.3 percent); 60.7 percent (interquartile range, 53.5 to 58.8 percent) received adjuvant therapy. At 32-month follow-up, the complication and failure rates were 40.1 percent (interquartile range, 26.7 to 58.6 percent) and 30.8 percent (interquartile range, 11.7 to 48.1 percent), respectively. The overall survival rate was 55 percent (interquartile range, 27.8 to 74 percent). Radiotherapy seemed to be a relative risk factor for complications (1.387; p = 0.014) and plate loss (1.585; p = 0.006). Crossing the midline seemed to be a relative risk factor for plate exposure (1.533; p = 0.000) and overall complications (1.385; p = 0.002). CONCLUSIONS: The results should be generalized cautiously. Alloplastic reconstructive surgery faces a remarkable lack of evidence. Relatively high complication and failure rates are areas of further concern.

Outcome of partial mandibular reconstruction with fibula grafts and implant-supported prostheses.

This study sought to evaluate the outcome of patients treated with fibula grafts for partial mandibular reconstruction and implant-supported prosthesis at a Danish university hospital. Patient inclusion criteria were: partial mandibular resection, reconstruction with a fibula graft, and treatment during the period 1998-2011. Patients with incomplete medical records were excluded. Thirty-six patients were included, of whom 16 were treated with an implant-supported prosthesis. Relevant presurgical, intraoperative, and postoperative parameters were registered. The fibula graft survival rate at the last follow-up (mean follow-up 22 months, range 0-89 months) was 97%. Half of the patients experienced non-severe complications such as loosening of osteosynthesis material, fistulae, and graft exposure. One of 37 fibula grafts in the 36 patients was removed due to infection. The implant survival rate was 96%; three of 67 implants were lost due to infection. Eight implants were not included in the prosthetic rehabilitation. Fibula graft surgery for mandibular reconstruction was found to be a reliable treatment modality with a high survival rate. Rehabilitation with implant-supported prostheses was characterized by high survival rates and few complications. The results obtained are comparable to those of previous studies.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.