Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1-3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4-7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

Depth of invasion as an independent prognostic factor in early-stage oral cavity squamous cell carcinoma.

PURPOSE: To determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. MATERIALS AND METHODS: 344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. RESULTS: Of 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01-58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01-1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11-1.83, p = 0.006). CONCLUSIONS: Depth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

Use of Banked Fibula for Improved Nasal Reconstruction Following Free Fibula Midface Reconstruction.

OBJECTIVE: Anterior maxillary deficiency caused by trauma or oncologic resection presents a complex reconstructive challenge. The authors present a technique for 2-stage midface reconstruction utilizing a vascularized free fibula flap for maxillary reconstruction, followed by nasal reconstruction at a second stage utilizing a banked fibula graft. METHODS: This case series utilizes a 2-stage technique for midface reconstruction. In the first stage, a fibula-free flap was used to reconstruct the maxilla with the excess banked in the abdomen. In the second stage, this bone graft was used to restore the nasal dorsum. RESULTS: Two patients were included in this series. Patient 1 was a 28-year-old man who presented after a remote gunshot wound to his face, resulting in complete loss of his anterior maxilla and nasal support with midface collapse. Patient 2 was a 65-year-old man who presented with squamous cell carcinoma of the hard palate with extension into the maxilla and nasal septum. In both cases, the flaps healed without complication, providing midface restoration. Placement of the banked fibula graft in a second stage resulted in restoration of dorsal nasal projection. CONCLUSION: The authors describe the use of "spare" fibula parts for nasal reconstruction after loss of the maxilla and cartilaginous septum. The use of the fibula bone as a graft to restore the nasal dorsum in a delayed manner allows for a better assessment of the esthetic needs after the massive swelling from the initial surgery has abated. Further, this approach eliminates the need for a second donor site for nasal reconstruction.

Paramaxillary CT-guided fine needle aspiration of head and neck lesions: technique, diagnostic yield, and safety profile.

Computed tomography (CT)-guided percutaneous biopsy of deep-seated head and neck lesions can be a less invasive and equally effective alternative to surgical techniques. There are multiple approaches for needle biopsy that target varying spaces within the head and neck while successfully avoiding critical anatomy. In the paramaxillary approach, the needle is advanced through the infrazygomatic buccal space, in between the maxilla and mandible. In this study, we examine the safety and diagnostic yield of FNA without core needle biopsy performed via the paramaxillary approach in 19 patients yielding 20 fine needle aspirates between 2014 and 2022. Of the fine needle aspirates, 85.0% (17/20) were diagnostic. Concordant histopathologic diagnosis was obtained in 100% (17/17) diagnostic fine needle aspirates. There were no postprocedural complications.

Microsurgical Head and Neck Reconstruction in Patients With Fanconi Anemia.

ABSTRACT: Patients with Fanconi anemia (FA) are at increased risk for head and neck cancers that often necessitate extensive reconstructions. Such patients have multiple comorbidities including anemia and thrombocytopenia frequently requiring bone marrow transplant, and they are at an increased risk of cancer recurrence and need for further extirpation. in the present study, charts from 3 patients with FA who underwent microvascular free tissue transfer by the senior author were retrospectively reviewed for pertinent pre- and peri-operative details in addition to functional and cosmetic outcomes. Two of these patients ultimately required metachronous free flap reconstructions for recurrence. All patients had acceptable functional and cosmetic outcomes following each instance of free flap reconstruction, thereby demonstrating the utility of microvas- cular free tissue transfer in patients with FA. The authors herein present each patient's clinical history in addition to a discussion of the current literature and an outline of our approach to these challenging cases.

Reconstruction of Full Thickness Scalp Defects in Extremely Elderly Patients Using Dermal Regeneration Templates.

The reconstruction of full thickness scalp defects following oncologic resection poses a unique challenge that is further magnified in "extremely elderly" patients, defined as those in at least their ninth decade of life, who are often unsuitable candidates for complex reconstruction. A "simpler" option is two-stage reconstruction: placement of Integra dermal regenerative template (Integra Life Science, Plainsboro, NJ) followed by a split thickness skin graft (STSG). This case series illustrates the success of this technique in the extremely elderly. A retrospective analysis of patients > 80 years at the time of surgery who underwent full thickness scalp reconstruction following tumor extirpation in a two-stage approach under the care of single surgeon from January 2010 to June 2019 was conducted. Variables reviewed were medical history, surgical treatment response, time to split thickness skin graft, follow up, and success of wound coverage. Fourteen patients, with a mean age of 87 years (range: 80 to 101, median: 87), met inclusion criteria. Split thickness skin grafts were placed after an average of 18 days. Twelve patients had successful two-stage reconstruction with 100% take. One patient developed a hematoma under a portion of the template that neither required reoperation nor delayed split thickness skin graft placement. A second suffered from insufficient vascularization of the template with delay to split thickness skin graft and incomplete wound closure. This two-stage approach is a successful primary reconstructive option for definitive management of full thickness scalp defects following oncologic resection in extremely elderly patients.

Adoption of transoral robotic surgery compared with other surgical modalities for treatment of oropharyngeal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. METHODS: Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. RESULTS: Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37-0.51, P < 0.0001; T3 vs. T1: O.R. 0.33, CI 0.28-0.38, P < 0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29-3.88, P = 0.004) and treatment at a high volume hospital (34-155 cases vs. 1-4 cases: O.R. 9.07, C.I. 3.19-25.79, P < 0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume versus low volume hospital (8.2% vs. 16.7% respectively, P = 0.001). CONCLUSIONS: Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC. J. Surg. Oncol. 2016;114:405-411. © 2016 Wiley Periodicals, Inc.

Idiopathic Chronic Parotitis: Imaging Findings and Sialendoscopic Response.

BACKGROUND/AIMS: The purpose of this study was to correlate imaging and sialendoscopic findings to therapeutic response in patients with idiopathic chronic parotitis. METHODS: We retrospectively reviewed 122 consecutive sialendoscopies performed in an academic medical center by two surgeons between 2008 and 2013. Forty-one (34%) and 54 (44%) patients were excluded on the basis of having parotid or submandibular sialolith, respectively. Nineteen cases were included in the study with idiopathic chronic parotitis. There was a median follow-up of 5 months. RESULTS: Computed tomography (CT) imaging had a sensitivity and specificity of 80.0 and 71.4%, respectively, for predicting abnormal findings on sialendoscopy, while magnetic resonance imaging (MRI) had 100% accuracy in a small set of cases. In glands with noticeable pathology present on preoperative imaging or sialendoscopy, 11 out of 12 glands (92%) treated experienced symptomatic improvement, while 3 out of 7 glands (43%) without pathology on imaging or endoscopy experienced symptomatic improvement (p = 0.038). CONCLUSIONS: Sialendoscopy for the treatment of idiopathic chronic parotid disease can improve pain and swelling with a higher frequency of success in patients with abnormalities noted on endoscopy. CT and MRI have a moderate degree of accuracy in predicting which patients will benefit from therapeutic sialendoscopy.

Retrospective Assessment of the Utility of Imaging, Fine-Needle Aspiration Biopsy, and Intraoperative Frozen Section in the Management of Parotid Neoplasms: The Weill Cornell Medical College Experience.

BACKGROUND/AIMS: Preoperative identification of malignant parotid lesions remains challenging, and thus, some surgeons use frozen section (FS) to assist them in their decision making. We evaluated the pathologic and cost benefit of FS after fine-needle aspiration (FNA) at our institution. METHODS: We assessed medical data for 260 patients undergoing parotidectomy with FS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for radiology, FNA, and FS. RESULTS: The sensitivities, specificities, and accuracies of FNA and FS were 75.0, 96.4, and 93.2%, and 75.0, 100, and 96.8%, respectively. FS detected 0% of FNA false negatives and 80% of false positives. The additional pathology charge for FS alone per correctly identified benign lesion after a positive FNA was USD 1,443. CONCLUSION: FNA and FS are more reliable in the prognostication of the final pathology than radiology. At our center, FS appears to be of limited clinical use after benign FNAs, but may be more useful after positive, indeterminate, and nondiagnostic FNAs.

Pectoralis major myocutaneous flap versus free fasciocutaneous flap for reconstruction of partial hypopharyngeal defects: what should we be doing?

BACKGROUND: Partial hypopharyngeal defects are most commonly reconstructed with the pectoralis major myocutaneous flap (PMMF) or free fasciocutaneous (FFC) flap. The purpose of this study is to determine the ideal method for reconstruction of partial hypopharyngeal defects by reviewing our institutional experience and the literature. METHODS: A retrospective review of partial hypopharyngeal reconstructions since 2009 was performed. A National Library of Medicine search of studies on partial hypopharyngeal reconstruction since 1988 was performed. Data on complications, diet, and speech were extracted and pooled. RESULTS: A total of 18 patients were studied-9 had PMMF reconstruction and 9 had FFC reconstruction. Operative time (8.75 vs. 13.0 hours, p = 0.0003) was shorter in the PMMF group. Pharyngocutaneous fistula developed in one PMMF patient (11.1%) and two FFC patients (22.2%). Late strictures occurred in three PMMF patients. Six patients in each group (66.7%) progressed to a regular diet. Three patients in each group produced tracheoesophageal speech after TEP. Literature review identified 36 relevant studies, with 301 patients reconstructed with PMMF and 605 patients with FFC. Pooled-data analysis revealed that PMMF had higher reported rates of fistula (24.7 vs. 8.9%, p < 0.0001) and requirement for second surgery (11.3 vs. 5.5%, p = 0.04). There was no difference in stricture rates or progression to regular diet. Fewer PMMF patients produced tracheoesophageal speech (17.5 vs. 52.1%, p < 0.0001). CONCLUSIONS: PMMF and FFC flaps are valid approaches to reconstructing partial hypopharyngeal defects, though rates in the literature of fistula, need for revisional surgery, and tracheoesophageal speech after laryngectomy are more favorable after free flap reconstruction.

Oral rehabilitation outcomes after free fibula reconstruction of the mandible without condylar restoration.

PURPOSE: Resection of the posterior mandible for tumor or osteonecrosis may include the mandibular condyle, an integral part of the temporomandibular joint (TMJ). Condylar reconstruction, including use of prostheses, the native condylar head, or part of the fibula, all have associated drawbacks including skull base erosion and the potential for ankylosis and TMJ dysfunction as well as the increased difficulty associated with trying to recapitulate the TMJ with high fidelity. We report our experience leaving a single side of the reconstructed mandible unsecured to the glenoid fossa, allowing the mandible to "hang." We hypothesized that a good functional recovery may be achieved with this simple approach while avoiding the potential for ankylosis and TMJ dysfunction. METHODS: A retrospective chart review of all patients undergoing free fibula reconstruction of the mandible with condylar removal was performed. Outcomes were determined by maximum interincisal opening, occlusion, and diet after full recovery. RESULTS: Six patients were studied. Two had condylar reconstruction with a contoured fibular head secured to the glenoid fossa. One of them had progressive postoperative trismus and ankylosis. One patient was reconstructed with the native condyle rigidly fixed to the fibula flap, complicated by avascular necrosis requiring condylar resection, with good function afterward. Three patients were left to "hang." All 3 had either normal or improved function after surgery. Two had slight ipsilateral deviation on mouth opening. CONCLUSIONS: Function can reliably be reestablished after segmental mandibulectomy and condylectomy with a vascularized fibula flap whose distal end is not precisely contoured or actively seated in the glenoid fossa, as a valid alternative to condylar reconstruction.

Characterizing Long-Term Swallowing and Voice Outcomes Following Anterior Transcervical Approach.

OBJECTIVES: (1) Assess the frequency and severity of long-term swallowing and voice complaints, follow-up care, risk factors for the development of long-term swallowing and voice complications in patients who underwent anterior transcervical approach (ACA). (2) Determine incidence of long-term swallowing and voice complications requiring follow-up otolaryngologic care and assess the frequency of otolaryngologic follow-up for postoperative swallowing and voice complaints. METHODS: Retrospective cohort study of patients between January 2017 and March 2020 who underwent ACA. Demographic information, data from preoperative evaluation, operative records, and data from postoperative visits were collected. Patients were contacted to complete the Eating Assessment Tool and the "Impairment" subset of the Voice Symptoms Scale. RESULTS: A total of 48 patients (10.6%) followed up with a head and neck surgeon for swallowing complaints and 31 patients (6.8%) for voice complaints. Otolaryngology follow-up for swallowing complaints among patients with at least 3 and 12 months of follow-up was 16.4% and 17.8%, respectively. Otolaryngology follow-up for voice complaints among patients with at least 3 and 12 months of follow-up was 11.7% and 11.9%, respectively. Swallowing function was abnormal in 40.7% at least 3 months after surgery and in 41.8% 12 months after. Voice function was abnormal in 55.7% of respondents at least 3 months after surgery and in 54.5% of respondents 12 months after. CONCLUSIONS: ACA is associated with otolaryngologic complications that include dysphagia and dysphonia. This study demonstrates that long-term swallowing and voice dysfunction appear to persist longer than what is noted by patient utilization of follow-up otolaryngologic care. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3201-3205, 2024.

Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta-analysis of individual patients' data.

BACKGROUND: Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs. METHODS: Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochran's Q test and I2 test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias. RESULTS: Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations. CONCLUSION: Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.

Financial (dis)incentives to surgical management of head and neck cancer care.

BACKGROUND: Patients with head and neck cancer (HNC) often require complex surgical reconstruction. This retrospective, cross-sectional study compares financial factors influencing HNC and breast cancer (BC) care to examine care disparities. METHODS: Pricing data from 2012 to 2021 was abstracted from the CMS Physician Fee Schedule Look-Up Tool. Nonprofit and research support was quantified by searching the NIH, IRS, and GuideStar databases. New York State Department of Health data from 2015 to 2019 was analyzed to compare costs, charges, and payer mix. RESULTS: HNC reconstructive procedures reimburse lower than comparable breast procedures (p < 0.05). Nonprofit and research support for HNC is disproportionately low relative to disease burden. Patients hospitalized for HNC surgical procedures generated higher costs and lower charges than patients with BC (p < 0.05). CONCLUSION: Comparatively low procedure reimbursement, low nonprofit support, and high cost of care for patients with HNC relative to patients with BC may contribute to care disparities for patients with HNC.

Multidisciplinary management of carotid body tumors: a single-institution case series of 22 patients.

OBJECTIVE: Carotid body tumors (CBTs) are rare, slow-growing neoplasms derived from the parasympathetic paraganglia of the carotid bodies. Although inherently vascular lesions, the role of preoperative embolization prior to resection remains controversial. In this report, the authors describe an institutional series of patients with CBT successfully treated via resection following preoperative embolization and compare the results in this series to previously reported outcomes in the treatment of CBT. METHODS: All CBTs resected between 2013 and 2019 at a single institution were retrospectively identified. All patients had undergone preoperative embolization performed by interventional neuroradiologists, and all had been operated on by a combined team of cerebrovascular neurosurgeons and otolaryngology-head and neck surgeons. The clinical, radiographic, endovascular, and perioperative data were collected. All procedural complications were recorded. RESULTS: Among 22 patients with CBT, 63.6% were female and the median age was 55.5 years at the time of surgery. The most common presenting symptoms included a palpable neck mass (59.1%) and voice changes (22.7%). The average tumor volume was 15.01 ± 14.41 cm3. Most of the CBTs were Shamblin group 2 (95.5%). Blood was predominantly supplied from branches of the ascending pharyngeal artery, with an average of 2 vascular pedicles (range 1-4). Fifty percent of the tumors were embolized with more than one material: polyvinyl alcohol, 95.5%; Onyx, 50.0%; and N-butyl cyanoacrylate glue, 9.1%. The average reduction in tumor blush following embolization was 83% (range 40%-95%). No embolization procedural complications occurred. All resections were performed within 30 hours of embolization. The average operative time was 173.9 minutes, average estimated blood loss was 151.8 ml, and median length of hospital stay was 4 days. The rate of permanent postoperative complications was 0%; 2 patients experienced transient hoarseness, and 1 patient had medical complications related to alcohol withdrawal. CONCLUSIONS: This series reveals that endovascular embolization of CBT is a safe and effective technique for tumor devascularization, making preoperative angiography and embolization an important consideration in the management of CBT. Moreover, the successful management of CBT at the authors' institution rests on a multidisciplinary approach whereby endovascular surgeons, neurosurgeons, and ear, nose, and throat-head and neck surgeons work together to optimally manage each patient with CBT.

Sequential second free fibula flap for the reconstruction of metachronous osteoradionecrosis of the mandible.

Osteoradionecrosis (ORN) of the mandible is a potentially catastrophic complication of external beam radiation therapy for head and neck malignancies. A 55-year-old man treated with chemoradiation for base-of-tongue cancer presented with a necrotic left mandibular body and underwent left mandibulectomy with right free fibula osteocutaneous flap reconstruction. Two and a half years later, he presented with right mandibular body ORN and underwent a second mandibular resection and subsequent reconstruction with a left fibula osteocutaneous free flap fixed in the midline to the previously placed contralateral fibula. He recovered well from all procedures. To the best of our knowledge, we report the first case of a patient with metachronous ORN of the mandible requiring resection and subsequent reconstruction with sequential free fibula flaps. Even in the presence of prior microvascular reconstructions, patients can successfully undergo additional reconstructive procedures to restore their function, appearance, and quality of life.

Identification of occult metastatic disease via lymphoscintigraphy-guided neck dissection in N0 oral squamous cell carcinoma.

BACKGROUND: The purpose of this study is to assess the efficacy of lymphoscintigraphy-guided neck dissection (LSG-ND) in the treatment of N0 oral squamous cell carcinoma. METHODS: A retrospective cohort study of patients with N0 oral squamous cell carcinoma (SCC) who had either LSG-ND or neck dissection (ND) at our institution between 2008 and 2020. RESULTS: Eighty-seven patients met criteria with N0 oral squamous cell carcinoma with no previous treatment or neck surgery (27 LSG-ND, 60 ND). Sentinel lymph nodes were identified on the contralateral side in 14.8% of patients with unilateral tumors in the LSG-ND group, with 22.2% of cases with unexpected lymphatic drainage outside ipsilateral levels I-III. No recurrences to date have occurred in the LSG-ND cohort, while 13.3% of patients with ND had regional recurrence (p = 0.04). CONCLUSIONS: LSG-ND provides a greater ability to identify occult metastatic disease with a significant reduction in regional recurrence in N0 oral SCC.

Establishing an Office-Based Framework for Resuming Otolaryngology Care in Academic Practice During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 health crisis abruptly disrupted the practice of otolaryngology. This article aims to define the changes needed to operate an academic otolaryngology practice safely and efficiently from within the epicenter of the pandemic. We define the areas of normal patient workflow that have been affected by COVID-19, and we offer mitigation strategies with attention paid to the specific needs of subspecialties. DATA SOURCES: The article includes data specific to the office practice metrics of the Weill Cornell Medicine Department of Otolaryngology-Head and Neck Surgery, as well as publically available data from New York Presbyterian Hospital system and the New York Times. REVIEW METHODS: Expert opinion. CONCLUSIONS: Through careful planning and execution, it is possible to reestablish safe otolaryngologic patient care during the COVID-19 pandemic. It will require a significant change from prior practice models for successful implementation. Additionally, telemedicine can be positively integrated into the treatment of otolaryngology diseases for new and established patients. IMPLICATIONS FOR PRACTICE: The information conveyed in this review can be used as a guide by large and small otolaryngology groups to identify aspects of the patient visit that are "at risk" due to COVID-19, and it suggests sensible responses that can be made without a significant disruption to normal practice. The methods used to identify vulnerabilities with the patient visit process can be applied to future unforeseen crises, such as a resurgence of COVID-19 or a novel pandemic.

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "early-stage" by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p < 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p < 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

Pain and Opioid Analgesic Use After Otorhinolaryngologic Surgery.

OBJECTIVE: To quantify pain and opioid use after otorhinolaryngologic surgery. To determine the effect of patient and surgical factors on primary outcomes. STUDY DESIGN: Prospective cohort. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Patients undergoing elective otorhinolaryngologic surgery were prospectively enrolled. Patients completed demographic surveys and psychometric questionnaires assessing attitudes toward pain and baseline anxiety and depression before surgery. After surgery, patients documented peak pain levels (0-100 mm, visual analog scale) and daily prescription and nonprescription analgesic requirements over a 2-week period. Average daily and cumulative pain and opioid use were calculated and compared among patient cohorts stratified by procedure and preoperative factors. RESULTS: A total of 134 patients were enrolled. Total tonsillectomy was associated with significantly higher pain scores and opioid consumption, as compared to all other procedures. There was moderate correlation between average cumulative pain and opioid use. Older patients required significantly fewer doses of opioids. There was no effect of sex, marital status, or education level on postoperative pain or opioid use. Psychometric instrument scores and chronic pain or analgesic use were not associated with significant differences in pain or opioid requirements. Most patients were prescribed substantially more opioids than they actually required. CONCLUSION: Postoperative pain following elective otorhinolaryngologic surgery decreases dramatically within the first week and requires only few days of opioid analgesia, with the exception of tonsillectomy. Almost all patients required fewer than 15 doses of opioids.