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 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.

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.

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.

A Retrospective Volume Matched Analysis of the Submental Artery Island Pedicled Flap as Compared to the Forearm Free Flap: Is It a Good Alternative Choice for the Reconstruction of Defects of the Oral Cavity and Oropharynx?

PURPOSE: The submental artery island pedicled flap (SMIF) is an underused alternative for reconstruction of head and neck defects after tumor ablation. The purpose of this study was to perform a comparative evaluation of reconstructive outcomes based on surgical site and ablative defect volume in patients who underwent reconstruction with the SMIF versus the forearm free flap (FFF). MATERIALS AND METHODS: A retrospective cohort study of all patients with oral cavity and oropharyngeal defects reconstructed with the SMIF and a cohort of patients with similar volume defects reconstructed with the FFF were compared for oncologic safety and viability of equivalent reconstructive outcomes. All statistical comparisons were assessed by analysis of variance and Fisher exact test. RESULTS: Average age was 61.8 years in the SMIF group versus 57.9 years in the FFF group. The most common defect was located in the tongue, with squamous cell carcinoma being the most common pathology identified. Flap volumes were similar (SMIF, 38.79 cm3; FFF, 39.77 cm3). Significant comparative outcomes identified with SMIF versus FFF reconstruction included shorter anesthesia times (815 vs 1,209 minutes; P < .001), shorter operative times (653 vs 1,031 minutes; P < .001), and less blood loss (223 vs 398 mL; P = .04). Postoperative Eastern Co-operative Oncology Group performance score increased more for the FFF than for the SMIF group (+0.33 vs + 1.25; P = .0019). Recipient site complication rates were lower for the FFF group (0.17 vs 0.42 per patient) but were not statistically relevant. There were equal rates of recurrence at the local surgical site and no differences in speech and swallowing function. Mean follow-up was 15.5 months. CONCLUSIONS: This is the first study to compare the SMIF with the FFF for reconstruction of oral cavity defects based on ablative volume deficit. The SMIF is a viable surgical option compared with the FFF that can be considered oncologically safe in the N0 neck, allowing for an excellent esthetic reconstruction, with decreased operative time, hospital stay, and donor site morbidity.

Is Long-Term Follow-Up Mandatory for Stage I Oral Tongue Cancer?

PURPOSE: The objective of this study was to analyze the outcomes and possible risk factors for late recurrence of pathologic stage I oral tongue squamous cell carcinomas (SCCs) in patients considered disease free at 3 years. MATERIALS AND METHODS: This retrospective study evaluated all patients with pathologic stage I oral tongue cancer within a tertiary care center from 2003 through 2013 who had been followed for a minimum of 36 months. RESULTS: One hundred twelve patients met inclusion criteria for long-term analysis. Despite the high overall survival of 92.2% for true pT1N0M0 disease, initial surgery failed in 25 of 112 patients (22.3%) who developed late disease recurrence (>36-month follow-up) locally (19.6%; n = 22), regionally (4.4%; n = 5), or as second primary disease (11.6%; n = 13). Eleven patients (50%) who had local recurrence could be salvaged with a second surgery, requiring no further treatment (mean, 48.7 months). Projected 10-year disease-free survival and overall survival were 61 and 89%, respectively. Thirty-three percent (n = 3 of 9) of deaths occurred in long-term patients considered disease free at 36 months. CONCLUSION: Stage I tongue SCC is more common in women and is associated with pre-existing leukoplakia. Although overall survival is excellent, a high failure rate from local recurrence or a new second primary is seen over an extended period. Long-term follow-up is mandatory because local salvage rates are excellent if SCC is diagnosed early. Regional failure carries a poor prognosis.

Surgical Site Infections in Patients Receiving Osteomyocutaneous Free Flaps to the Head and Neck. Does Choice of Antibiotic Prophylaxis Matter?

PURPOSE: The most appropriate prophylactic antibiotic for clean-and-contaminated head and neck osteomyocutaneous free flap (OFF) tissue transfer procedures is unclear. The purpose of this study was to determine whether the choice of perioperative antibiotic was related to recipient surgical site infection (SSI) in patients receiving an OFF to the head and neck. MATERIALS AND METHODS: This retrospective cohort study evaluated SSI in relation to the perioperative antibiotic received from July 2010 through October 2013 at a tertiary care medical center. Minimum follow-up was 6 months. SSI was defined by the Centers for Disease Control and Prevention wound infection criteria. Perioperative antibiotic selected, duration of use, OFF performed, medical comorbidities, and SSIs were recorded and analyzed. RESULTS: One hundred two patients (64 men, 38 women) met the inclusion criteria. Forty patients developed an SSI. Analysis of variance showed that age (P = .64), gender (P = .97), use of alcohol (P = .87), final pathology (P = .3), cardiovascular disease (P = .33), and diabetes mellitus or immune dysfunction (P = .95) did not have a significant association with the development of a postoperative wound infection. On univariate analysis, non-head and neck primary malignancies showed a significant risk for SSI (P = .03), with previous head and neck surgery (P = .05) and oral tobacco use (P = .06) having trends for increased risk of SSI. Clindamycin antibiotic was strongly associated with the development of an SSI, with 50% of that cohort developing a recipient SSI (odds ratio = 7.0; P < .002), regardless of duration of use. The rate of development of a recipient SSI with cefazolin was 25% and that with ampicillin plus sulbactam was 19%. CONCLUSION: A statistically relevant number of patients who developed a recipient SSI received clindamycin as perioperative antibiotic prophylaxis. An antibiotic regime other than clindamycin should be considered in patients with an allergy to penicillin or cephalosporin who are undergoing an OFF procedure to the head and neck.

The Value of the "Papillon" Anterolateral Thigh Flap for Total Pharyngolaryngectomy Reconstruction: A Retrospective Case Series.

PURPOSE: The tubed, buried anterolateral thigh (ALT) flap is a popular reconstruction method for total pharyngolaryngectomy defects. The "papillon"-designed ALT flap, described by Hayden et al, offers an alternative method of using the ALT flap in this situation. We report our early experience with the papillon ALT flap in a patient cohort. PATIENTS AND METHODS: On retrospective review, all patients who underwent reconstruction of circumferential total pharyngolaryngectomy defects with the papillon ALT flap from February 2012 to February 2015 were identified from our departmental database. Demographic and clinical data, operative details, and complications were analyzed from the records. RESULTS: Seven patients were included in this study. The mean length of hospital stay was 15 days (range, 10 to 32 days). Acute complications occurred in 5 of 7 patients, namely, partial flap loss managed by a pectoralis flap (1 of 7 [14%]); an early pharyngocutaneous fistula (4 of 7 [57%]) managed by simple repair, wound packing, or delayed repair; and a donor-site hematoma (1 of 7 [14%]). At follow-up (range, 2 to 24 months), there was 1 stricture formation, but no chronic fistula. All patients were able to swallow orally. CONCLUSIONS: Early results using the papillon ALT flap suggest that this technique is a viable alternative to the standard tubed ALT flap design. The advantages of this design include the following: 1) it offers simultaneous vascularized skin to resurface anterior neck skin deficiency without resorting to additional tissue elsewhere; 2) direct monitoring of the ALT flap is possible; and 3) any pharyngocutaneous fistula is exteriorized to the surface without compromising the internal neck structures and can be easily identified and repaired directly in the office.

A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN).

BACKGROUND: We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3-positive RM-SCCHN patients, respectively. METHODS: Three dose levels (500, 1,000, and 1,500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2 ml) and GM-CSF (100 µg/m2) were administered subcutaneously q2 weeks for a total of four vaccinations in HPV16 and MAGE-A3-positive RM-SCCHN patients, respectively. RESULTS: Nine and seven patients were enrolled in the HPV16 and MAGE-A3 cohorts, respectively. No dose-limiting toxicities were observed, and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). In those patients who received all four vaccinations, 80 % (4/5) of the HPV16 cohort and 67 % (4/6) of the MAGE-A3 cohort developed antigen-specific T cell and antibody responses to the vaccine. Significant concordance between T cell and antibody responses was observed for both groups. No clear dose-response correlation was seen. All patients progressed by RECIST at first repeat imaging, except for one patient in the MAGE-A3 500 µg cohort who had stable disease for 10.5 months. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days, respectively, and for the HPV16 cohort 80 and 196 days, respectively. CONCLUSIONS: GL-0810 and GL-0817 were well tolerated in patients with RM-SCCHN with T cell and antibody responses observed in the majority of patients who received all four vaccinations.

The Hybrid Submental Flap for Tongue Reconstruction.

PURPOSE: To describe a hybrid submental flap using pedicled and microvascular techniques to circumvent a restricting vascular anatomy and increase the rotational arc of the skin paddle. METHODS AND MATERIALS: This case report and literature review describes a hybrid submental flap. A standard submental island flap was planned and elevated for reconstruction of an acquired lateral tongue defect secondary to oncologic ablation. Aberrant venous anatomy was encountered in which the submental vein drained directly into the internal jugular vein, thus limiting the arc of rotation. The facial vein was ligated at its branch point from the internal jugular vein and anastomosed to the external jugular vein. Medical records were reviewed, including clinical and operative notes. A standard free flap postoperative protocol was adhered to, including aspirin, enoxaparin sodium, flap checks, and internal monitoring using a venous Flow Coupler (Synovis Micro Companies Alliance, Inc, Birmingham, AL). RESULTS: The hybrid submental flap was used effectively for lateral tongue reconstruction. Hybridization of the flap allowed for increased pedicle length and mobilization of the skin paddle. The flap remained well perfused postoperatively, with excellent speech and swallow function after adjuvant chemoradiotherapy. CONCLUSION: The hybrid submental flap is technically feasible and can be a valuable bailout procedure when aberrant vascular anatomy limits the arc of rotation. Ligation and anastomosis of the vein, versus the artery, is more likely to be required because of the more variable drainage patterns and potential valves that would prevent retrograde flow in a Y-V procedure. Retrograde arterial perfusion through the angular branch of the facial artery, by ligation of the submental artery at its proximal takeoff from the facial artery, is a well-documented method to gain cephalad arc of rotation in cases of restrictive arterial anatomy.

Quality of life factors and survival after total or extended maxillectomy for sinonasal malignancies.

PURPOSE: Total and extended maxillectomy results in significant morbidity that can have an effect on quality of life factors. Modern reconstructive techniques have ameliorated this effect, but they have not been quantified. The purpose of the present study was to evaluate the quality of life factors and survival of patients undergoing total or extended maxillectomy for malignant disease. MATERIALS AND METHODS: A retrospective study was performed of all patients who had undergone total or extended maxillectomy at a tertiary care cancer center from January 2008 to May 2013. The minimum follow-up period was 6 months. The quality of life factors analyzed included swallowing function and diet consistency, pain control, and postoperative complications. RESULTS: A total of 25 patients (13 women and 12 men) met the inclusion criteria. Using the American Joint Committee on Cancer staging system, 76% of the patients had stage IV disease. Of the 25 patients, 13 received a free tissue transfer, 11 an obturator flap, and 1 a regional flap. None of the patients with a free tissue transfer experienced failure. The tumor size had no systemic influence on the reconstructive method chosen (P = .32 to P = .98). The median follow-up period was 41 weeks (range 24 to 252). One death was recorded, and 10 patients were lost to follow-up. Eleven patients progressed to a regular diet. Fifteen patients required a tracheostomy, and all were decannulated at a mean of 14 days postoperatively. One patient had dental implants placed. The type of reconstruction did not influence swallowing function (P = .49) or long-term pain (P = .38). The mean pain score was 4.9 ± 2.7. Pain management proved difficult in 7 patients. Also, 6 patients developed a surgical site infection, 3 of whom required a return to the operating room. Seven patients were readmitted to the hospital for complications; however, the reconstructive method did not influence the incidence of complications (P = .64). CONCLUSIONS: The inevitable morbidity, with respect to quality of life factors, that result from the disfiguring effects of total or extended maxillectomy can be deemed acceptable by patients. We recommend discussing all reconstructive options regarding the management of late-stage maxillary malignancies and the potential effect they can have on patients' quality of life.

Treatment of cT1N0M0 tongue cancer: outcome and prognostic parameters.

PURPOSE: The objective of the present study was to summarize the treatment and outcomes of cT1N0M0 tongue cancer for which the management is less defined. MATERIALS AND METHODS: A total of 65 consecutive cases of cT1 tongue cancer were retrospectively reviewed. The Fisher exact, χ(2), and Wilcoxon tests were used to statistically analyze the data. RESULTS: The tumor depth had a significant relation to the presence of neck metastasis (P < .05). A 3-mm cutoff point provided better predictive value, with a sensitivity of 92.9% and specificity of 43.1%. The biopsy depth combined with palpation was accurate in determining the tumor depth preoperatively in 87.7%. On multivariate analysis, only the tumor site (ventral tongue) and the presence of erythroleukoplakia had any significant relation to disease-free survival (P = .010). CONCLUSIONS: Elective neck dissection should be considered for patients with cT1N0 oral tongue squamous carcinoma with a biopsy depth of 3 mm or greater. The biopsy depth, combined with the clinical examination findings, is a useful method to help determine the tumor depth preoperatively.

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.

Florid follicular lymphoid hyperplasia of the palate: review of the literature and report of an illustrative case.

OBJECTIVE: The aim of this report was to review oral follicular lymphoid hyperplasia, with emphasis on palatal lesions. METHOD AND MATERIALS: A comprehensive search was performed on PubMed for case reports and case series of palatal follicular lymphoid hyperplasia published in the English language literature. Relevant data from collated articles was sought, including patient demographics, clinical manifestations, imaging modalities and findings, comorbidities, etiopathogenesis, lesional management, and lesional outcome. A new palatal case has also been provided to illustrate several features of this lesion. RESULTS: In total, 32 cases were assembled to establish clinicopathologic correlations, representing the largest aggregation of published cases. Most of the affected patients were at least 60 years old and with a decisive female predilection. The majority of lesions were ≤ 3 cm, appearing as normal color, purple-red or red, and varied from soft to firm. Notably, 32% of palatal follicular lymphoid hyperplasias were associated with denture wear, and lesional recurrence was recorded in 16% of cases. To date, none of the reported cases of palatal follicular lymphoid hyperplasia has undergone malignant transformation. CONCLUSIONS: Palatal follicular lymphoid hyperplasias often arise as a reactive process. Critical histopathologic and histochemical assessments are necessary to establish benignity. Postoperatively, clinicians should follow patients for at least 5 years for recurrence and remain vigilant for neoplastic change as several published accounts of non-oral follicular lymphoid hyperplasias have undergone malignant transformation, usually to lymphoma.

Histological pattern of tumor inflammation and stromal density correlate with patient demographics and immuno-oncologic transcriptional profile in oral squamous cell carcinoma.

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignancy, with emerging interest in the characterization of its tumor microenvironment. Herein, we present a comprehensive histological analysis of OSCC stromal density and inflammation and their relationship with patient demographics, clinicopathologic features and immuno-oncologic signatures. Materials-methods: Eighty-seven completely excised OSCC tissues were prospectively collected and scored for histopathologic inflammatory subtypes [HIS]-inflamed (INF), immune-excluded (IE) and immune-desert (ID), peritumoral stromal inflammation (PTSI), and peritumoral stromal fibrosis (PTSF). Scoring of inflammation was complemented by Semaphorin 4D immunohistochemistry. NanoString differential gene expression (DGE) analysis was conducted for eight OSCC cases representative of the inflammatory and stromal subtypes and the demographic groups. Results: PTSF correlated with male gender (p = 0.0043), smoking (p = 0.0455), alcohol consumption (p = 0.0044), increased tumor size (p = 0.0054), and advanced stage (p = 0.002). On the contrary, PTSI occurred predominantly in females (p = 0.0105), non-drinkers (p = 0.0329), and small tumors (p = 0.0044). Transcriptionally, decreased cytokine signaling, and oncogenic pathway activation were observed in HIS-IE. Smokers and males displayed decreased global immune-cell levels and myeloid-cell predominance. Conclusion: Our work describes OSCC stromal and inflammatory phenotypes in correlation with distinct patient groups and DGE, highlighting the translational potential of characterizing the tumor microenvironment for optimal patient stratification.

A retrospective analysis of squamous carcinoma of the buccal mucosa: an aggressive subsite within the oral cavity.

PURPOSE: Squamous carcinoma of the buccal mucosa is relatively uncommon in the North American population. It is considered an aggressive cancer, with difficulty in obtaining negative surgical margins and poor locoregional control. This single-institution retrospective analysis attempted to identify prognostic variables, treatment outcomes, and survival patterns of patients with buccal carcinoma. MATERIALS AND METHODS: A retrospective chart review of all patients with buccal carcinoma treated in the Department of Oral and Maxillofacial Surgery, University of Maryland from 1992 through 2008 was conducted. Thirty newly diagnosed and previously untreated patients were reviewed and their outcomes data were analyzed. RESULTS: Thirteen female and 17 male patients were identified (mean age, 64 yr). Eighteen patients had early-stage disease (stages I to II). Fifteen patients (50%) developed recurrence, with 13 patients developing local recurrence despite 80% of patients achieving negative surgical margins. The overall nodal metastasis rate was 43%, with an occult nodal rate of 32%. Overall 2- and 5-year survival rates were 69% and 53%, respectively. Thirty-nine percent of patients not receiving adjuvant therapy developed recurrence. Early recurrence tended to occur more commonly and was a poor prognostic indicator of successful salvage. CONCLUSIONS: Buccal carcinoma is an aggressive disease, with high rates of locoregional disease recurrence independent of surgical margin status. Elective neck dissection and adjuvant therapy should be considered for early-stage disease. Successful salvage is rare in cases of early recurrence.

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.

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.

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.

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.