Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Is hardware colonization associated with latent hardware complications and removal in maxillomandibular free flap reconstruction?

BACKGROUND: The relationship between hardware colonization, latent hardware complications, and hardware removal remains unclear following osteocutaneous free flap reconstruction of the jaws. METHODS: Retrospective cohort study of all patients undergoing free flap reconstruction of the maxilla or mandible from 2016 to 2021. RESULTS: A total of 240 subjects were included. Hardware colonization was associated with latent hardware complication in bivariate (p ≤ 0.001) and multivariate analysis (p ≤ 0.001). Time to latent hardware complication was 6.87 months earlier in colonized subjects (p ≤ 0.001). Of the 35 subjects undergoing hardware removal, 25 initiated but failed conservative therapy, and resolution of symptoms was achieved in 24 subjects after one operative intervention and 33 subjects after repeat intervention if indicated. CONCLUSIONS: Hardware colonization increases the risk and onset of latent hardware complication. Prompt hardware removal may improve outcomes by leading to faster resolution of symptoms without the burden and cost of conservative therapies.

Is Preoperative Serum Albumin Predictive of Adverse Outcomes in Head and Neck Cancer Surgery?

BACKGROUND: Patients with head and neck cancer are at increased risk of malnutrition due to tumor burden and surgical morbidity. PURPOSE: The purpose of this study was to evaluate the association between preoperative serum albumin and 30-day adverse outcomes in patients undergoing head and neck cancer surgery. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing an ablative head and neck cancer procedure were included. Patients who had an unclear tumor location based on coding or missing outcome data were excluded. PREDICTOR VARIABLE: The primary predictor variable was preoperative albumin categorized as low (<3.4 g/dL), intermediate (3.4 to 3.9 g/dL), or high (>3.9 g/dL). OUTCOME VARIABLE: The primary outcome variable was intensive care unit (ICU)-level complications scored using the Clavien-Dindo classification system. This is a tool used to grade surgical complications, with grade IV and V complications defined as requiring ICU-level care. COVARIATES: Covariates were demographic (age, sex, body mass index), medical (smoking, functional status, weight loss), and perioperative (concurrent procedures, tumor location, reconstructive modality). ANALYSES: Descriptive, bivariate, and multiple logistic regression with bootstrap resampling statistics were used to evaluate the association between albumin and adverse outcomes. A significance level of P ≤ .05 was significant. RESULTS: A total of 4,491 subjects met inclusion criteria and had a documented albumin. There were 435 subjects with low albumin levels, 1,305 with intermediate levels, and 2,751 with high levels. In bivariate analysis, low albumin levels were associated with an increased risk of ICU-level complications, any complication, extended length of stay, and adverse discharge disposition (all P ≤ .001), while high levels were protective (all P ≤ .001). In bootstrapped multivariate analysis using intermediate albumin as the reference group and adjusting for demographics, tumor location, and reconstructive modality among others, low albumin levels were an independent predictor of ICU-level complications (P = .008, odds ratio, 1.64; 95% confidence interval, 1.14 to 2.40), while high levels were protective (P = .014, odds ratio, 0.689; 95% confidence interval, 0.521 to 0.923). CONCLUSIONS: Preoperative serum albumin was an independent predictor of adverse outcomes following ablative head and neck cancer procedures.

Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma.

OBJECTIVE: The purpose of this study is to identify the immuno-oncologic (IO) signature at the surgical tumor margin (TM) of oral squamous cell carcinoma (OSCC) that is involved in the process of malignant transformation. STUDY DESIGN: Under institutional review board approval, TM of 73 OSCC were investigated using immunohistochemistry for the immune biomarker, programmed death ligand-1 (PD-L1). NanoString 770 IO-focused gene set was analyzed in 5 pairs of TM and invasive tumor (T). PD-L1 regulation in response to interferon-gamma (IFN-γ) was investigated in an oral potentially malignant cell line (OPMC). RESULTS: Programmed death ligand-1 expression in the epithelial margin directly correlated with its expression in the underlying immune cells (P = .0082). Differential gene expression showed downregulation of PD-L1 and IFN-γ 6 gene signature in the TM relative to T pair.CD8 and macrophages were higher in TM. CNTFR, LYZ, C7, RORC, and FGF13 downregulation in T relative to TM. TDO2, ADAM12, MMP1, LAMC2, MB21D1, TYMP, OASL, COL5A1, exhausted_CD8, Tregs,and NK_CD56dim were upregulated in T relative to TM. Finally, IFN-γ induced upregulation of PD-L1 in the OPMC. CONCLUSIONS: Our work suggests a role for IFN-γ in PD-L1 upregulation in OPMC and presents novel IO transcriptional signatures for frankly invasive OSCC relative to TM.

Cytokine profiling in plasma distinguishes the histological inflammatory subtype of head and neck squamous cell carcinoma and a novel regulatory role of osteopontin.

Head and neck squamous cell carcinoma (HNSCC) can be classified according to the histological inflammatory subtype (HIS) into inflamed (HIS-INF) or immune excluded (HIS-IE). HIS-IE was previously associated with higher levels of soluble Semaphorin 4D (HsS4D) in plasma, and higher transcriptional levels of osteopontin (OPN) in the tumor tissue, compared to HIS-INF. The goal of the current study is to investigate whether the HIS inflammatory subtype can be distinguished by a differential cytokine panel in peripheral blood. Retrospectively collected five HIS-INF and five HIS-IE tumor tissue with paired plasma were included in the study. Five healthy donors (HD) and five autoimmune/chronic inflammatory conditions (AI/CI) were controls. The ELISA-Luminex™ system was used to detect 40 traditional cytokines in plasma. Human cytokine array (104 cytokines) was used for the conditioned medium (CM) of the HNSCC HN6 cell line. Semaphorin 4D (Sema4D) siRNA and recombinant human osteopontin (rh-OPN) were used to investigate the effect of OPN on Sema4D expression. The HIS-IE cytokine profile was higher than HIS-INF but comparable to AI/CI. HIS-INF had the lowest cytokine levels. HIS-IE was differentially higher in IP-10 and IL8 compared to HD, while HIS-INF was higher in IL-10. Sema4D inhibition in HN6 resulted in a decrease of OPN in the CM of HN6, and treatment with rh-OPN rescued Sema4D in HN6 cell lysate and associated CM. In conclusion, the current work demonstrates a novel association between the HIS subtypes and a differential pattern of cytokine expression in plasma. These findings can open new avenues for HNSCC patient stratification and hence provide better personalized treatment.

Is the prevention of condylar sag with maxillomandibular fixation the key to functional reconstruction of a mandibular disarticulation resection?

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes of the use of the free fibula flap for reconstruction with mandibular disarticulation resections. STUDY DESIGN: A retrospective chart cohort review was performed in patients reconstructed with a fibula free flap for a mandibular disarticulation resection at an academic tertiary care institution over a 5-year period. RESULTS: Twenty-four patients were included in the study. Fourteen patients were treated for benign pathology, and 10 cases were malignant. Average follow-up was 20 months. Virtual surgical planning/3-dimensional models were used in all cases. Maxillomandibular fixation (MMF) with surgical wires was used in 65% (n = 13/20) of the dentate patients. Average maximum interincisal opening was 28.2 mm in patients receiving radiation and 38.7 mm in the nonradiated group (P = .01). No patient developed joint ankylosis. Neocondyle position was an average of 11.7 mm from condylar fossa, radiographically. Seventeen of the dentate patients (85%) had reproducible class I occlusion. Occlusion was superior in patients placed into MMF compared with those with elastics or no MMF (P = .06) and independent of the position of the neocondyle (P = .19). CONCLUSIONS: The vascularized fibula flap can be used to provide functional reconstruction of the mandibular condyle defect. The use of at least 2 weeks of MMF maintains an adequate occlusion irrespective of the fibula-glenoid fossa position. The neocondyle does not need to directly abut the articular disc or fossa for adequate functional outcomes.

Ghost Cell Odontogenic Carcinoma Arising in a Previous Calcifying Odontogenic Cyst: A Case Report and Review of Literature.

Ghost cell odontogenic carcinoma (GCOC) is a rare malignant tumor of odontogenic origin, with only about 50 cases reported in the English literature so far. Histologically, it is characterized by ghost cells, dentinoid deposits, high grade malignant cellular features, and areas of necrosis and invasion. Having common histological features with other odontogenic ghost cell lesions (OGCL) like calcifying odontogenic cyst (COC) and dentinogenic ghost cell tumors, it is crucial to recognize GCOC malignant features, as it can be destructive and invasive, sometimes showing distant metastases and high recurrence rate. For this reason, it may entail more aggressive surgical approach and multimodal therapeutic regimen. Here we present a case report of GCOC arising in a previous COC, treated with surgical excision that showed persistence and recurrence after two years. The clinical and histological features of this rare occurrence are presented, in addition to the surgical approach, and a summary of literature review of OGCL.

Oral squamous cell carcinoma in patients aged 45 and younger: Prognosis, survival, and quality of life.

OBJECTIVE: To perform a detailed analysis of the epidemiology, tumor biology, treatment, overall survival, and quality of life in a young patient (age ≤45 years) cohort with oral squamous cell carcinoma (OSCC). STUDY DESIGN: A retrospective cohort study between 1992 and 2017 at an academic tertiary care center. RESULTS: In total, 80 patients were included (36 female and 44 male) with stage I (American Joint Committee on Cancer eighth ed.) disease and lateral tongue was most common presentation. Mean follow-up was 6.28 years. The overall disease recurrence rate was 28.7% (23 of 80). Human papillomavirus was positive in 22% of patients tested. Free flap reconstruction was not associated with improved margin status (P = .62) but significant for recurrent disease (P < .04). Overall 2-year survival was significantly poorer in patients with close/positive margin status and free flap reconstruction. Patients with early-stage disease (stage II) requiring adjuvant radiotherapy, chemotherapy (all stages), or flap reconstruction (Stage III patients) had significantly worse 5-year survival rates. CONCLUSIONS: OSCC in young patients (age ≤45 years) is an increasingly more common disease that occurs in patients without known risk factors. Despite their earlier presentation of disease pathology, constant vigilance and standard aggressive treatment similar to other age groups will result in similar and improved outcomes and survival.

Impact of the Novel Coronavirus 2019 (COVID-19) Pandemic on Head and Neck Cancer Care.

OBJECTIVE: The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility. STUDY DESIGN: This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes. SETTING: This single-center study was conducted at a tertiary care academic hospital in a large metropolitan area. METHODS: The study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes. RESULTS: In total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an 8.4% treatment modification rate among cases presented at the tumor conference. There was a 61.3% (347 from 898) reduction in outpatient clinic visits and a 63.4% (84 from 230) reduction in procedural volume compared to the prior year. Similarly, the operative volume decreased by 27.0% (224 from 307) compared to the previous year. CONCLUSION: Restrictions related to the COVID-19 pandemic resulted in limited treatment modifications. Transition to virtual tumor board format observed an increase in case presentations. While there were reductions in operative volume, there was a larger proportion of surgical cases for malignancy, reflecting the prioritization of oncologic care during the pandemic.

Soluble Sema4D in Plasma of Head and Neck Squamous Cell Carcinoma Patients Is Associated With Underlying Non-Inflamed Tumor Profile.

Semaphorin 4D (Sema4D) is a glycoprotein that is expressed by several tumors and immune cells. It can function as a membrane bound protein or as a cleaved soluble protein (sSema4D). We sought to investigate the translational potential of plasma sSema4D as an immune marker in plasma of patients with head and neck squamous cell carcinoma (HNSCC). Paired peripheral blood and tumor tissue samples of 104 patients with HNSCC were collected at the same time point to allow for real time analysis. Scoring of the histological inflammatory subtype (HIS) was carried out using Sema4D immunohistochemistry on the tumor tissue. sSema4D was detected in plasma using direct ELISA assay. Defining elevated sSema4D as values above the 95th percentile in healthy controls, our data showed that sSema4D levels in plasma were elevated in 25.0% (95% CI, 16.7-34.9%) of the patients with HNSCC and showed significant association with HIS immune excluded (HIS-IE) (p = 0.007), Sema4D+ve tumor cells (TCs) (p = 0.018) and PD-L1+ve immune cells (ICs) (p = 0.038). A multi-variable logistic regression analysis showed that HIS was significantly (P = 0.004) associated with elevated sSema4D, an association not explained by available patient-level factors. Using the IO-360 nanoString platform, differential gene expression (DGE) analysis of 10 HNSCC tumor tissues showed that patients with high sSema4D in plasma (HsS4D) clustered as IFN-γ negative tumor immune signature and were mostly HIS-IE. The IC type in the HsS4D paired tumor tissue was predominantly myeloid, while the lymphoid compartment was higher in the low sSema4D (LsS4D). The Wnt signaling pathway was upregulated in the HsS4D group. Further analysis using the IO-360, 770 gene set, showed significant non-inflamed profile of the HsS4D tumors compared to the LsS4D. In conclusion, our data reveals an association between sSema4D and the histological inflammatory subtype.

The deep circumflex iliac artery free flap in maxillofacial reconstruction: a comparative institutional analysis.

PURPOSE: The aim of the present study was to perform a comparative analysis of the utility, outcomes, and complications of DCIA (deep circumflex iliac artery) flap for the reconstruction of maxillofacial defects between two institutions that continue to use the DCIA flap as a reconstructive resource. MATERIALS AND METHODS: This retrospective analysis included a total of 68 patients (mean age 51.1 years) at the University Hospital of Parma, Parma, Italy, and the University of Maryland, Baltimore, USA, between January 2010 and April 2019. RESULTS: No statistical differences were found in relation to the site of reconstruction (p = 0.09), bone graft quantity (p = 0.93), rehabilitation with dental implants (p = 0.464), length of hospitalization (p = 0.086), BMI (0.677), swallow function (p = 0.419), medical comorbidities (p = 0.933), pre-existing radiation (p = 0.691), adjuvant treatment (p = 0.298), ECOG-PS pre-and post-surgery (p = 0.329; p = 0.545), and flap failure: one partial failure observed (p = 0.412) and donor site morbidities (p = 0.742). A noted trend to increased risk of hernia without the use of a primary mesh repair was observed (p = 0.059). CONCLUSION: The DCIA free flap represents a useful and reliable reconstructive flap for maxillofacial reconstruction. Reconstructive microvascular surgeons should be proficiently trained in this flap technique for its consideration as a first-line option in maxillofacial reconstruction.

Self-Retained Voice Prosthesis in the Decompression of the Odontogenic Keratocyst: A Technical Note.

Decompression of the odontogenic keratocyst has been a long-standing treatment modality in the armamentarium of oral-maxillofacial surgeons. Many different types of effective decompression tubes have been described in the literature. They reduce the size of the cystic lesion by decreasing the intraluminal pressure, induce histologic structural changes in the epithelial lining of the cyst, and allow for bone deposition to occur from the periphery of the cystic cavity. However, many of these have pitfalls including tube dislodgement, traumatization of the oral mucosa, and mucosal overgrowth. We describe a novel technique using an indwelling voice prosthesis (Inhealth Technologies, Carpinteria, CA) to decompress odontogenic keratocysts. We found that our method provides effective decompression using appropriate-length prostheses fit to the cyst dimensions. It provides improved comfort in patients, with less mucosal irritation or overgrowth, improved ease of irrigation, and improved retention that often does not require sutures.

Face transplantation: general review and long-term management of the dental patient.

Facial allotransplantation (FA) is an emerging alternative modality following severe loss of hard and soft tissues. Although there are vast numbers of publications on the surgical aspects of this technique, limited information is available in the literature with regard to the long-term dental care of affected patients following postoperative stabilization and return to their locally based clinical milieu. The objective of this report is to review patient demographics, etiologies, structural graft components, immunosuppressive strategies, donor tissue pathogenicity, neurologic recovery, potential complications, and present clinical guidelines for dental management. Additionally, a brief discussion of the preparation of the donor mask, and cutaneous and intraoral images of allograft rejection have been provided.

An Alternative Approach to Carotid Endarterectomy in the High Carotid Bifurcation.

BACKGROUND: Surgical exposure of a high carotid bifurcation (HCB) for carotid endarterectomy (CEA) can be technically challenging due to the presence of bony structures in the most cranial portion of the neck and is associated with significant morbidity making carotid artery stenting (CAS) a common alternative. However, a high transverse neck incision with subplatysmal flaps facilitates CEA in these patients without additional exposure techniques. We present a high transverse neck incision with subplatysmal flaps as an alternative to the standard surgical exposure of the carotid bifurcation to facilitate CEA in patients with HCB. METHODS: Four patients with carotid bifurcations located cranial to the C3-4 vertebral interspace (identified on preoperative imaging) requiring intervention underwent CEA using a high transverse neck incision through an existing skin crease with subplatysmal flap elevation. CEA was performed in a standard fashion with bovine pericardial patch. RESULTS: Two male and 2 female patients with an average age of 65 years successfully underwent CEA using this incision. One patient underwent concurrent carotid body tumor excision. None of the patients required mandibulotomy or hyoid bone resection. Two patients required division of the posterior belly of the digastric muscle. There were no perioperative complications. Primary patency was 100% in the 4 patients with surveillance studies, and mean follow-up of 160 days (range 54-369 days). There were no significant cranial nerve injuries. No patient required conversion to an endovascular procedure due to inaccessibility of the lesion or subsequent interventions for incomplete endarterectomy. CONCLUSIONS: A high transverse incision with subplatysmal flaps is a safe, effective, and cosmetically preferable surgical approach in patients with HCB requiring carotid artery intervention and may be an alternative to CAS.

Gingival squamous cell carcinoma: an unexpected clincal presentation.

Squamous cell carcinoma (SCC) is an aggressive tumor and represents the most common oral malignancy found by dental health care providers. Timely detection is paramount to reduce patient comorbidities of regional and distant metastases and improve survival rates. To augment recognition of early stage of gingival SCC (GSCC), this article features the somewhat innocuous clinical findings in a 60-year-old female.