Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalinfixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (\u3c45 \u3eyears). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression

Subtotal Parathyroidectomy and Relocation of the Parathyroid Remnant for Renal Hyperparathyroidism: modification of a traditional operation

Abstract Background We describe a modification of the conventional subtotal parathyroidectomy operation where the parathyroid gland(s) remnant is repositioned with intact vascular supply to a plane superficial to the infrahyoid strap muscles and immediately under the skin incision. This technique called Subtotal Parathyroidectomy and Remnant Relocation (SPARE) retains all the metabolic advantages of the conventional operation with the added advantage of easier identification of a recurrent hyperplastic remnant if re-exploration becomes necessary. Methods In the SPARE technique, four parathyroid glands were identified and the quality of each gland and the length of each vascular pedicle to the parathyroid glands were assessed. The optimal parathyroid gland was relocated to a plane superficial to the strap muscles. The remainder of the glands were removed. Results In total, 30 patients with hyperparathyroidism secondary to renal failure (HSRF) underwent parathyroidectomy with the SPARE technique. The mean age was 53.1±12.5 years and median follow-up was 17.1 months (range 1-78.9 months). There were no recurrent laryngeal nerve (RLN) injuries or hematomas. The pre- and post-operative value for corrected calcium and PTH were 158.4±109.4 pmol/L and 11.4±12.1 pmol/L, respectively (p < 0.05). Three recurrences were noted (10.0%), with a mean time to recurrence of 15.3±6.6 months. One patient had excision of the remnant parathyroid glands performed under local anaesthetic (29 min); one had re-exploration performed under general anaesthetic (81 min), and one was managed medically. Conclusion We described a novel parathyroidectomy technique for patients with HSRF, which provides the advantages of conventional subtotal parathyroidectomy while mitigating the challenges of thyroid bed re-exploration when recurrences arise

Exploring patient values and perceptions with facial nerve palsy to help guide management: An Australian perspective

**Background**: Facial nerve palsy (FNP) leads to a combination of aesthetic and functional deficits with profound psychosocial consequences. Significant advances have been made in restoring dynamic function through a range of facial reanimation solutions. Patient-reported severity scales are predetermined metrics that provide limited insight into patient values and perceptions. A qualitative study was conducted to elicit the experiences of patients with FNP and explore their views and motivations for seeking therapy. **Methods**: Participants were sourced from the Sydney Head and Neck Cancer Institute Database, Australia. Eligibility for the study included age over 18 years and a diagnosis of complete FNP. Semi-structured interviews were conducted and the transcripts were subjected to thematic text analysis. **Results**: Nineteen patients consented to participate in the study. One was excluded due to an isolated marginal mandibular nerve palsy. Five main themes emerged: eye symptoms, fear of judgement and social withdrawal, aversion to further invasive surgeries, the need for multidisciplinary streamlined care and lack of public awareness. **Conclusion**: Eye symptoms and the social consequences of FNP carry significant impact on both patients’ personal and professional lives. There is a paucity of services that can support patients across the complex spectrum of problems seen in FNP

Implantable Doppler Ultrasound Monitoring in Head and Neck Free Flaps: Balancing the Pros and Cons.

OBJECTIVES/HYPOTHESIS: Free flap transfer offers a versatile option for reconstruction in head and neck surgery, with success rates over 95%. There remains a substantial re-exploration rate of roughly 5% to 15%, with early recognition of compromise essential to flap survival. Monitoring techniques are highly desirable, with the gold standard being clinical monitoring. The Cook-Swartz Doppler (CSD) probe utilizes Doppler technology to inform clinicians about real-time flow. We aim to describe our adoption of this technology in 100 consecutive free flaps. STUDY DESIGN: Prospective case series. METHODS: Prospective data were collected from July 2014 to June 2015 on 100 consecutive free flaps performed at a head and neck unit in London, Ontario. All patients had a CSD inserted for arterial and venous monitoring. RESULTS: A total of 100 free flaps were performed on 99 patients. Sensitivity was 87.1% and specificity was 85.7%. Positive predictive value was 98.8% and negative predictive value was 33.3%. False-negative and false-positive rate were 1.0% and 12.0%, respectively. The exploration rate was 12%, with no flap loss and two partial debridements. The CSD was helpful in management in 9% of cases and was clinically unhelpful in 11% of cases, with 10 of 11 abnormal signals ignored. There were three unique CSD complications; one retained wire, one pedicle laceration during extraction, and one clot around the probe interrupting signal. CONCLUSIONS: The CSD is a helpful adjunct to clinical monitoring but has unique complications, which were not previously described. Pros and cons must be considered for new centers adopting this technology. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1854-E1859, 2021

Evolution of Head and Neck Cutaneous Squamous Cell Carcinoma Nodal Staging&mdash;An Australian Perspective

Cutaneous squamous cell carcinoma of the head and neck (HNcSCC) is one of the commonest malignancies. When patients present with regional metastatic disease, treatment escalation results in considerable morbidity and survival is markedly reduced. Owing to the high incidence, Australian institutions have been at the forefront of advocating for reliable, accurate, and clinically useful staging systems that recognise the distinct biological characteristics of HNcSCC. As a result, an extensive body of literature has been produced over the past two decades, which has defined critical prognostic factors, critiqued existing staging systems, and proposed alternative staging models. Notwithstanding, a suitable staging system has proved elusive. The goal of cancer staging is to group patients according to cancer characteristics for which survival differs between groups (distinctiveness), consistently decreases with increasing stage (monotonicity), and is similar within a group (homogeneity). Despite implementing major changes based on published data, the latest edition of the American Joint Committee on Cancer (AJCC) staging manual fails to satisfy these fundamental requirements. This review chronologically explores and summarises the Australian contribution to prognostication and nodal staging of HNcSCC and highlights the ongoing challenges

Perineural invasion in oral squamous cell carcinoma : quantitative subcategorisation of perineural invasion and prognostication

Background: Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub-categorization of PNI improves risk stratification. Methods: PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease-specific survival (DSS) as the primary endpoints. Results: PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high-risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post-operative radiotherapy (PORT). Conclusions: Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation.7 page(s

Assessment of shoulder function following scapular free flap.

BACKGROUND: The scapular system free flap has been increasing in popularity to reconstruct short segment mandibular bony defects. It is important to assess donor site morbidities systematically. METHODS: Prospective cohort study using objective measures of range of motion (ROM) and shoulder strength were measured. Subjective disability was evaluated with validated questionnaires-Neck Disability Impairment Index and Shoulder Pain and Disability Index. RESULTS: Twenty-six patients were recruited-19 with scapular tip and 7 with lateral border scapular free flap. Decreased ROM on the operated side was noted for shoulder abduction, shoulder flexion, and external rotation. No significant difference was noted for shoulder extension. Strength was reduced for shoulder flexion, shoulder abduction, and external rotation. Subjective measurements did not indicate significant shoulder function disruption. CONCLUSION: Patients with scapular free flap reconstruction did not experience significant shoulder morbidity. Measures of shoulder ROM and power were objectively affected; however, subjective measures of shoulder disability were not significantly affected

Characterization of temporal soft tissue space to aid the design of implants aimed at restoring function in facial paralysis

Aim: Facial paralysis inflicts devastating functional and aesthetic deficits. Several solutions are being developed, including implantable bionics to correct paralytic lagophthalmos. The temporal fossa has been postulated to be a suitable location for such devices. Anatomical studies of this fossa have limited application in the design of implants with complex internal components that are constrained by specific functional requirements. In this study, we assess the variation in temporal fossa volumes that could be utilized by a functional implantable device.Methods: CT scans of 18 hemifaces were used to create a 10-point template for measuring tissue thickness in the temporal fossa. Using this data, linear models were used to perform a volumetric analysis of the temporalis muscle and temporal fat pad concerning key anatomical landmarks.Results: The estimated temporalis muscle, temporal fat, and total combined volumes were 19.2 mL (95%CI: 10.4-32.9), 10.3 mL (95%CI: 6.1-16.1), and 29.5 mL (95%CI: 16.7-48.9) respectively, consistent with other publications. The temporalis muscle volume increases rapidly and then plateaus moving posteriorly along the zygomatic arch and superiorly along the lateral orbital rim. Whereas the temporal fat increases similarly along the lateral orbital rim, it increases at a uniform rate along the zygomatic arch.Conclusion: Simple geometric modelling of the functional soft tissue space in the temporal fossa is feasible and can be readily applied to aid in the development of implantable devices

Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma

Background: The American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7). Methods: Analysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell\u27s concordance index (C-index). Results: AJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell\u27s C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell\u27s C of 0.65 and 0.69, respectively). Conclusions: The AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma

Background The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. Methods A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease‐free survival (DFS). The minimal‐P approach was used to investigate the optimal lymph node ratio threshold. Results Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11‐2.38; P = .01) and OS (HR 1.63; 95% CI 1.03‐2.58; P = 0.04) on multivariable analysis. Conclusion The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio \u3e6% is a significant threshold to categorize patients into low and high risk