Non-adherence to recommended adjuvant radiation after total laryngectomy.

OBJECTIVES: Investigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). METHODS: Previously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. RESULTS: Among 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72-0.93) analysis. CONCLUSIONS: Within the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Addressing the Neck: An NCDB Study of Clinically Node-Negative Supraglottic Squamous Cell Carcinoma.

OBJECTIVE: Identify the proportion of patients undergoing elective neck dissection (END) in surgically managed supraglottic squamous cell carcinoma (SCCa), assess associations between patient, tumor, and treatment factors with END, and assess associations between neck management and overall survival (OS). STUDY DESIGN: Retrospective study. SETTING: National Cancer Database (NCDB) 2019 Participant User File. METHODS: Patients with previously untreated, clinically node-negative (cN0) supraglottic SCCa treated with partial laryngectomy were queried from NCDB. Patients without known neck management and who underwent total laryngectomy were excluded. Patient and tumor factors associated with END were evaluated by logistic regression analysis. Univariable Cox proportional hazard analysis was used to examine associations between patient factors and OS, and factors with P < .05 were included on multivariable analysis. RESULTS: A total of 1352 patients met eligibility criteria. Eight hundred eleven (60%) patients had END performed with occult nodal metastasis identified in 177 (22%) patients. END was more likely to be performed at academic centers than nonacademic centers (odds ratio: [1.66], 95% confidence interval [CI]: 1.32-2.09, P < .001). On multivariable analysis, patients who underwent adjuvant radiation had worse OS (hazard ratio [HR]: 1.45, 95% CI: 1.13-3.29, P = .017). END was associated with improved OS overall on univariable analysis (HR: 0.83, 95% CI: 0.69-0.98, P = .026), but not on multivariable analysis. CONCLUSION: In this NCDB study, 22% of cN0 supraglottic SCCa patients had occult nodal metastatic disease. Despite this, 40% of patients do not receive END at the time of primary resection. Patients who receive END for supraglottic SCCa are more likely to avoid adjuvant radiation without impacting OS.

Reirradiation after osteocutaneous free flap reconstruction for locally recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer poses difficult management. Even after salvage surgery, many patients are considered high-risk for further recurrence and benefit from reirradiation, despite the sequelae such as chronic wounds, tissue necrosis, osteoradionecrosis and vascular damage associated with re-irradiation. Free flaps not only enable the reconstruction following salvage surgery, but there has been limited studies suggesting that free flap reconstruction may reduce the amount of reirradiation complications. However, there are no studies to date specifically examining the effects of osteocutaneous free flap reconstruction upon reirradiation outcomes. MATERIALS AND METHODS: In this retrospective study, patients with recurrent head and neck cancer that had a history of prior head and neck radiation who underwent salvage surgery with osteocutaneous free flaps followed by reirradiation were identified. Descriptive statistics were performed to assess outcomes. RESULTS: Five patients met criteria. Complications included chronic wound infection in one patient, fistula in one patient, plate exposure in two patients and plate removal in one patient. No patients had osteoradionecrosis or carotid rupture after reirradiation. There was an association between complications and further local disease recurrence. All patients were tube feed dependent at their most recent follow-up and two patients were tracheostomy dependent 12 months post-irradiation. Two patients had disease recurrence. Median overall survival was 16 months after reirradiation. CONCLUSIONS: Osteocutaneous free flap surgery with reirradiation may result in high rates of complications and low functional status with an equivocal improvement in survival. Larger studies are needed to substantiate these findings and assess the risk-benefit analysis.

Unplanned Return to Hospital After Same Day Oral Cavity Resection: A Dual Institution Study.

OBJECTIVES: Primary objective: describe rates of 30-days unplanned readmission following outpatient resection of oral cavity cancer. Secondary objective: evaluate for patient and treatment factors associated with readmission. METHODS: Retrospective, dual-institution cohort study of 2 tertiary care referral centers involving adult patients undergoing resection of oral cavity cancer with plans for same-day discharge. Consecutive sample of 77 patients included. Primary outcome was unplanned readmission to emergency room or inpatient stay in the 30 days following surgery. Comparison testing was used between return and non-return groups. RESULTS: Among 77 patients treated with outpatient surgery for oral cavity cancer, 19 (25%) returned to the hospital within 30 days. Among the reasons for return, 16 (80%) were directly related to surgery, and 4 (20%) were related to perioperative medical complications not directly related to a surgical site. Among the 25 patients also undergoing sentinel lymph node biopsy with their oral cavity resection, none returned to the hospital for neck-related complications. While most patients could be safely observed and discharged after return to the hospital, 8 patients (10%) required inpatient readmission. No significant differences between return and non-return groups were identified, although there was a trend toward shorter driving distance from hospital for the return group (47.6 miles vs. 69.5 miles, P = 0.097). CONCLUSION: Unplanned return to the hospital following outpatient oral cavity resection is prevalent and primarily driven by postoperative primary resection site concerns. Among patients selected for same day discharge, no definite population at highest risk of unplanned return was identified.

Guideline-compliant adjuvant chemotherapy for resected high risk oral cavity cancer: Homefield advantage.

PURPOSE: Factors that are associated with failure to receive guideline-compliant adjuvant chemotherapy after resection of high-risk oral cavity cancer are understudied. Here, we performed a retrospective cohort study of surgically treated patients with oral cavity squamous cell carcinoma to determine rates of guideline-compliant adjuvant chemotherapy and to examine patient factors associated with receiving guideline-compliant chemotherapy. STUDY DESIGN: Retrospective cohort. SETTING: Two tertiary care referral centers. METHODS: Patients with resected high-risk oral cavity squamous cell carcinoma and known adjuvant therapy details were included. Extranodal extension or positive margins were considered high-risk features for which adjuvant chemoradiation was indicated. Patient factors were examined to determine associations with receiving on-guidelines treatment. Univariable and multivariable logistic regression were used to determine significance of associations. RESULTS: 75 patients were included. 36 (48 %) patients received guideline-compliant cisplatin. In total, 39 (52 %) patients did not receive guideline-compliant chemotherapy. On multivariable analysis, meeting with a university medical oncologist was significantly associated with the receipt of guideline-compliant cisplatin (OR 6.38, 95 % CI 2.26-20.0, p < 0.001). CONCLUSION: Adherence to on-guidelines treatment can be difficult to achieve in patients with advanced stage head and neck cancer. Meeting with university medical oncology is associated with an increased chance of receiving guideline-compliant chemotherapy.

Acute Achilles tendon rupture: Skip the surgery?

Nonoperative management for acute Achilles tendon rupture results in patient-reported outcomes similar to surgery at 1 year-but higher rates of rerupture.

Trends in Positive Surgical Margins in cT3-T4 Oral Cavity Squamous Cell Carcinoma.

OBJECTIVE: Positive surgical margins in oral cavity squamous cell carcinoma are associated with cost escalation, treatment intensification, and greater risk of recurrence and mortality. The positive margin rate has been decreasing for cT1-T2 oral cavity cancer over the past 2 decades. We aim to evaluate positive margin rates in cT3-T4 oral cavity cancer over time, and determine factors associated with positive margins. STUDY DESIGN: Retrospective analysis of a national database. SETTING: National Cancer Database 2004 to 2018. METHODS: All adult patients diagnosed between 2004 and 2018 who underwent primary curative intent surgery for previously untreated cT3-T4 oral cavity cancer with known margin status were included. Logistic univariable and multivariable regression analyses were performed to identify factors associated with positive margins. RESULTS: Among 16,326 patients with cT3 or cT4 oral cavity cancer, positive margins were documented in 2932 patients (18.1%). Later year of treatment was not significantly associated with positive margins (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96-1.00). The proportion of patients treated at academic centers increased over time (OR 1.02, 95% CI 1.01-1.03). On multivariable analysis, positive margins were significantly associated with hard palate primary, cT4 tumors, advancing N stage, lymphovascular invasion, poorly differentiated histology, and treatment at nonacademic or low-volume centers. CONCLUSION: Despite increased treatment at academic centers for locally advanced oral cavity cancer, there has been no significant decrease in positive margin rates which remains high at 18.1%. Novel techniques for margin planning and assessment may be required to decrease positive margin rates in locally advanced oral cavity cancer.

Going Off Guidelines: An NCDB Analysis of Missed Adjuvant Therapy Among Surgically Treated Oral Cavity Cancer.

OBJECTIVE: Patient factors associated with failure to receive adjuvant therapy after oral cavity cancer resection remain understudied. Here, we identified rates of missed adjuvant therapy, determined factors associated with missed therapy, and assessed associations with survival. STUDY DESIGN: Retrospective cohort. SETTING: National Cancer Database. METHODS: Patients with resected oral cavity squamous cell carcinoma and known adjuvant therapy status were included. T3-4 stage, N2-3 stage, and lymphovascular invasion were considered indications for adjuvant radiation. Extranodal extension or positive margins were considered indications for chemoradiation. Patient factors were examined for associations with missed adjuvant therapy. Overall survival was evaluated by Cox proportional hazard analysis. RESULTS: A total of 53,503 patients were included. 27.5% missed adjuvant therapy altogether, and 26.7% with a documented indication for chemoradiation missed chemotherapy. Factors associated with missed adjuvant therapy were age, white race, low income, metropolitan population, increasing comorbidities, travel distance, lip primary, and treatment at the academic facility. Factors associated with missed chemotherapy were age, female sex, nontongue subsite, and treatment at a nonacademic center. Among patients with indications for adjuvant radiation, missed radiation was associated with worse overall survival (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.31-1.53). Among patients with indications for adjuvant chemoradiation, missed chemotherapy was associated with worse overall survival (HR: 1.19, 95% CI: 1.09-1.29). CONCLUSION: Missed adjuvant therapy occurs frequently after oral cavity resection. Patients treated at academic centers may be at risk of missed therapy related to travel distance, though these patients are more likely to receive adjuvant chemotherapy when indicated. Missed adjuvant therapy is associated with worse survival.

Postoperative Chyle Leak Rate Following Neck Dissection for Squamous Cell Carcinoma Versus Papillary Thyroid Cancer.

OBJECTIVES: Compare the rates of post-operative chyle leak following therapeutic lateral neck dissection during treatment of papillary thyroid carcinoma (PTC) versus squamous cell carcinoma (SCC) of the head and neck. METHODS: A retrospective analysis of 226 consecutive neck dissections in 201 patients who underwent therapeutic neck dissection involving at least levels II-IV with a final pathologic diagnosis of mucosal SCC of the head and neck or PTC from 2010 to 2020. Specific cases of chyle leak were reviewed. Surgical factors associated with chyle leak were analyzed using logistic regression analysis. Duration of chyle leak was assessed by the Kaplan-Meier curve, and time-to-resolution was analyzed by Cox proportional hazard analysis. RESULTS: Postoperative chyle leak was encountered in 15 (6.6%) neck dissections, eight (12.3%) in PTC, and seven (4.3%) in SCC. High-volume chyle leak and chyle leak requiring operative intervention were only encountered in neck dissections performed for PTC. Chyle leak was significantly associated with PTC on univariable analysis (OR 3.08, p = 0.037), but not on multivariable analysis (OR 1.35, p = 0.711). High-volume chyle leak and the need for operative intervention were associated only with PTC patients (OR 23.6, p = 0.006; OR 18.09, p = 0.023 respectively). Median duration of chyle leak was 12.1 days among patients with SCC, and 20.5 days among patients with PTC (p = 0.089). CONCLUSIONS: Among 201 patients undergoing therapeutic neck dissection, chyle leak was associated with PTC pathology on univariable but not multivariable analysis. However, high-volume leaks and leaks requiring operative intervention only occurred among patients with PTC. LEVEL OF EVIDENCE: level III Laryngoscope, 133:2959-2964, 2023.

Factors Leading to Gastrostomy Tube and Tracheostomy Requirements in Patients Treated Initially With Radiotherapy and Salvaged With Surgery and Free Flap Reconstruction.

OBJECTIVE: Patients with recurrent oropharyngeal cancer can achieve survival benefits from surgical salvage, and often require simultaneous free-flap reconstruction. Resection and reconstruction can impact function, leading to tube dependence. PRIMARY OBJECTIVE: describe rates of tracheostomy and gastrostomy tube dependence after oropharyngeal resection and free flap after prior radiation. SECONDARY OBJECTIVE: evaluate patient, tumor, and treatment factors associated with tube dependence. STUDY DESIGN: Retrospective, multi-institutional cohort study. Patients treated from 2003 to 2020. Average follow-up 21.4 months. SETTING: Five tertiary care centers. METHODS: Consecutive cohort of patients undergoing resection and simultaneous free-flap reconstruction for oropharyngeal squamous cell carcinoma after head and neck radiation. PRIMARY OUTCOMES: gastrostomy tube dependence and tracheostomy or tracheostoma 1 year after surgery. Univariable and multivariable logistic regression were performed to identify factors associated with dependence. RESULTS: 89 patients underwent oropharyngectomy and free-flap reconstruction; 18 (20%) underwent total laryngectomy as part of tumor extirpation. After surgery, 51 patients (57%) lived 12 months. Among patients alive at 12 months, 22 (43%) were at least partially-dependent on gastrostomy tube, and 15 (29%) had either tracheostomy or tracheostoma. On multivariable analysis, extensive glossectomy (OR 16.6, 95% CI 1.83-389, p = 0.026) and total laryngectomy (OR 11.2, 95% CI 1.71-105, p = 0.018) were associated with long-term gastrostomy tube. No factors were associated with long-term tracheostomy on multivariable analysis. CONCLUSION: Even among long-term survivors after salvage resection and free-flap reconstruction, rates of tube dependence are significant. This multi-institutional review is the largest such study to the date and may help inform shared decision-making. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2141-2147, 2023.

A Multi-institutional Analysis of Late Complications in Scapula, Fibula, and Osteocutaneous Radial Forearm Free Flaps.

OBJECTIVES: (1) Evaluate the association of flap type with late complications in patients undergoing osseous head and neck reconstruction with the fibula free flap (FFF), osteocutaneous radial forearm free flap (OCRFFF), and scapula free flap (SFF). (2) Compare the prevalence of late complications based on minimum duration of follow-up. STUDY DESIGN: Retrospective cohort study. SETTING: Multiple academic medical centers. METHODS: Patients undergoing FFF, OCRFFF, or SFF with ≥6-month follow-up were stratified by type of flap performed. The association of flap type with late complications was analyzed via univariable and multivariable logistic regression, controlling for relevant clinical risk factors. Additionally, the frequency of late complications by minimum duration of follow-up was assessed. RESULTS: A total of 617 patients were analyzed: 312 (50.6%) FFF, 230 (37.3%) OCRFFFF, and 75 (12.2%) SFF. As compared with the SFF, the FFF (adjusted odds ratio [aOR], 3.05; 95% CI, 1.61-5.80) and OCRFFF (aOR, 2.17; 95% CI, 1.12-4.22) were independently associated with greater odds of overall late recipient site wound complications. The SFF was independently associated with the lowest odds of hardware exposure when compared with the FFF (aOR, 2.61; 95% CI, 1.27-5.41) and OCRFFF (aOR, 2.38; 95% CI, 1.11-5.12). The frequency of late complications rose as minimum duration of follow-up increased until plateauing at 36 months. CONCLUSIONS: This multi-institutional study suggests that the long-term complication profile of the SFF and OCRFFF compares favorably to the FFF. The SFF may be associated with the fewest overall late recipient site complications and hardware exposure, while the FFF may be associated with the most of these 3 options.

Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.

Perioperative Outcomes in Patients Who Underwent Fibula, Osteocutaneous Radial Forearm, and Scapula Free Flaps: A Multicenter Study.

Importance: Studies comparing perioperative outcomes of fibula free flaps (FFFs), osteocutaneous radial forearm free flaps (OCRFFFs), and scapula free flaps (SFFs) have been limited by insufficient sample size. Objective: To compare the perioperative outcomes of patients who underwent FFFs, OCRFFFs, and SFFs. Design, Setting, and Participants: This cohort study assessed the outcomes of 1022 patients who underwent FFFs, OCRFFFs, or SFFs for head and neck reconstruction performed at 1 of 6 academic medical centers between January 2005 and December 2019. Data were analyzed from September 17, 2021, to June 9, 2022. Main Outcomes and Measures: Patients were stratified based on the flap performed. Evaluated perioperative outcomes included complications (overall acute wound complications, acute surgical site infection [SSI], fistula, hematoma, and flap failure), 30-day readmissions, operative time, and prolonged hospital length of stay (75th percentile, >13 days). Patients were excluded if data on flap type or clinical demographic characteristics were missing. Associations between flap type and perioperative outcomes were analyzed using logistic regression, after controlling for other clinically relevant variables. Adjusted odds ratios (aORs) with 95% CIs were generated. Results: Perioperative outcomes of 1022 patients (mean [SD] age, 60.7 [14.5] years; 676 [66.1%] men) who underwent major osseous head and neck reconstruction were analyzed; 510 FFFs (49.9%), 376 OCRFFFs (36.8%), and 136 SFFs (13.3%) were performed. Median (IQR) operative time differed among flap types (OCRFFF, 527 [467-591] minutes; FFF, 592 [507-714] minutes; SFF, 691 [610-816] minutes). When controlling for SSI, FFFs (aOR, 2.47; 95% CI, 1.36-4.51) and SFFs (aOR, 2.95; 95% CI, 1.37-6.34) were associated with a higher risk of flap loss than OCRFFFs. Compared with OCRFFFs, FFFs (aOR, 1.77; 95% CI, 1.07-2.91) were associated with a greater risk of fistula after controlling for the number of bone segments and SSI. Both FFFs (aOR, 1.77; 95% CI, 1.27-2.46) and SFFs (aOR, 1.68; 95% CI, 1.05-2.69) were associated with an increased risk of 30-day readmission compared with OCRFFFs after controlling for Charlson-Deyo comorbidity score and acute wound complications. Compared with OCRFFFs, FFFs (aOR, 1.78; 95% CI, 1.25-2.54) and SFFs (aOR, 1.96; 95% CI, 1.22-3.13) were associated with a higher risk of prolonged hospital length of stay after controlling for age and flap loss. Conclusions and Relevance: Findings of this cohort study suggest that perioperative outcomes associated with OCRFFFs compare favorably with those of FFFs and SFFs, with shorter operative times and lower rates of flap loss, 30-day readmissions, and prolonged hospital length of stay. However, patients undergoing SFFs represented a more medically and surgically complex population than those undergoing OCRFFFs or FFFs.

Tuft Cells Are Present in Submandibular Glands Across Species.

Tuft cells are bottle-shaped, microvilli-projecting chemosensory cells located in the lining of a variety of epithelial tissues and, following their identification approximately 60 years ago, have been linked to immune system function in a variety of epithelia. Until recently, Tuft cells had not been convincingly demonstrated to be present in salivary glands with their detection by transmission electron microscopy only shown in a handful of earlier studies using rat salivary glands, and no follow-up work has been conducted to verify their presence in salivary glands of other species. Here, we demonstrate that Tuft cells are present in the submandibular glands of various species (i.e., mouse, pig and human) using transmission electron microscopy and confocal immunofluorescent analysis for the POU class 2 homeobox 3 (POU2F3), which is considered to be a master regulator of Tuft cell identity.

The use of a simultaneous fascia lata-free flap with cochlear implantation after radical Mastoidectomy.

Patients undergoing cochlear implant after prior radical mastoidectomy are at increased risk of device infection requiring device explant. Various techniques including two-stage operations have been used. We report the novel technique with use of a vascularized fascia lata free flap for a patient undergoing cochlear implantation with radical mastoidectomy.

Quality of life after segmental mandibulectomy and free flap for mandibular osteonecrosis: Systematic review.

OBJECTIVE: Review QOL outcomes among patients undergoing segmental mandibulectomy and bony free flap reconstruction for ONJ. DATA SOURCES: PubMed was searched for MeSH terms "Quality of life," "Osteonecrosis," "Osteoradionecrosis," "Bisphosphonate-associated osteonecrosis of the jaw," "Free tissue flaps," and "Mandibular reconstruction." REVIEW METHODS: English language studies with QOL outcomes data for patients undergoing free flap reconstruction for advanced ONJ were included. 197 records were initially screened; 18 full texts assessed; 10 full texts included. PRISMA guidelines were followed. RESULTS: Ten studies were included in this systematic review: six retrospective, three retrospective with comparison groups, and one prospective. In studies with comparison groups, ONJ patients have worse self-reported QOL than the general population as well as head and neck cancer patients without ONJ. Nearly all patients with QOL measurements (220/235 patients) had ONJ from prior radiation. Segmental mandibulectomy and bony free flap improved overall QOL in over half of patients, as well as pain associated with ONJ in 70-75 % of patients. Surgery did not improve long-term effects of radiation such as chewing, swallowing, and salivary production. Donor site morbidity rarely affects QOL. CONCLUSIONS: Osteonecrosis of the jaw (ONJ) worsens quality-of-life, and advanced disease often requires segmental mandibulectomy and bony free flap reconstruction. Patients and surgeons may expect improvement in some, but not all, domains of patient-reported QOL by the use of segmental mandibulectomy and reconstruction for advanced ONJ.

The role of matrixmetalloproteinase-2 expression by fibroblasts in perineural invasion by oral cavity squamous cell carcinoma.

OBJECTIVES: The mechanisms of perineural invasion (PNI) in oral cavity squamous cell carcinoma are only partially understood, and no studies have specifically investigated the role of perineural fibroblasts in PNI. Here, we identified fibroblasts within the microenvironment of perineural invasion and assessed their expression of matrix metalloproteinase-2 (MMP-2). MATERIALS AND METHODS: Tumor specimens from 12 patients with oral cavity squamous cell carcinoma and pathologically-confirmed perineural invasion were stained by immunohistochemistry (IHC) for vimentin (positive control) and MMP-2. Scoring was quantified and compared at nerves involved with PNI and nerves uninvolved with PNI. RESULTS: All 12 patients had perineural fibroblasts around involved and uninvolved nerves as marked by vimentin IHC staining. Perineural fibroblasts had detectable MMP-2 expression at areas of perineural invasion in all 12 patients, but no patients had MMP-2 expression by fibroblasts at nerves without PNI. CONCLUSION: MMP-2 is expressed by fibroblasts within the microenvironment of perineural invasion, and MMP-2 expression by fibroblasts is a possible mechanism of perineural invasion by oral cavity squamous cell carcinoma. MMP-2 may be an anti-cancer target among oral cavity squamous cell carcinoma patients with PNI.

"Incidentally discovered medullary thyroid carcinoma in the post-operative Graves' patient - A case report".

OBJECTIVE: To report a very rare case of incidentally discovered Medullary Thyroid Carcinoma after total thyroidectomy in a patient with Graves' disease, review available literature, and present readers with management information. RESULTS: Medullary Thyroid Carcinoma in the setting of Graves' disease is a rare scenario. Only fifteen total cases besides ours has been described in literature, and only six other cases were incidentally discovered. CONCLUSIONS: When Medullary Thyroid Carcinoma is incidentally discovered in the setting of Graves' disease, retroactive workup should begin with postoperative calcitonin, CEA level, testing for RET mutation, and a comprehensive neck ultrasound as soon as the diagnosis is made.