First Phase Development of a Patient-reported Outcome Measure for Midface Oncology.

Background: Facial cancer surgery involving the midface (comprising the lower eyelids, nose, cheeks, and upper lip) can have debilitating life-changing functional, social, and psychological impacts on the patient. Midface symptoms are inadequately captured by existing patient-reported outcome measures (PROMs). PROMs are increasingly used for individual patient care, quality improvement, and standardized reporting of treatment outcomes. This study aimed to present our findings from the first phase of the development of a midface, specifically periocular and nasal, PROM. Methods: After international guidance for PROM development, the first phase comprised identification of salient issues and item generation. Fifteen patients who had midface surgery and 10 clinicians from various specialties with more than 5 years' experience treating these patients were recruited. Semi-structured interviews explored aesthetic, functional, social, and psychological outcomes, with specific attention to deficiencies in current PROMs. Thematic analysis was used to develop an item pool, and group interviews with clinicians were carried out to create and refine PROM scales. Results: Qualitative data from patient interviews were grouped into aesthetic, functional, and psychosocial domains for the eyelids and nose. Ninety-nine draft items were generated across these domains. Following focus group discussions, the final version of the midface-specific PROM contained 31 items (13 eye-specific, 10-nose-specific, eight general midface items). Conclusions: This midface-specific PROM is valuable in assessing and comparing patient-reported outcomes in those who have undergone complex resection and reconstruction of the midface. This PROM is currently undergoing field testing.

Associations between patient-level health literacy and diagnostic time intervals for head and neck cancer: A prospective cohort study.

BACKGROUND: Health literacy (HL) comprises skills and knowledge required to understand, access, and make decisions about healthcare. Our aim was to examine associations between patient HL and time intervals (defined in the Aarhus statement) along the pathway to treatment of head and neck cancer (HNC). METHODS: A prospective cohort study was conducted from October 2018 to March 2020. Participants completed the Health Literacy Questionnaire (HLQ®) and described key events and dates along the pathway to treatment using validated questionnaires. Correlations between six diagnostic time intervals and domains of HL were explored, and factors predicting exceeding maximum acceptable timeframes were assessed using logistic regression. RESULTS: One hundred patients with a diagnosis of HNC within the preceding 6 months were recruited. HLQ® Domain 2 (sufficient information to manage health) was significantly negatively associated with four intervals: the patient interval (first symptom to first presentation), primary care interval (first presentation to referral to secondary care), diagnostic interval (first presentation to diagnosis), and total interval (first symptom to treatment onset); correlation coefficients -0.25 to -0.27 (P < 0.05). Domain 8 (ability to find good information) was significantly negatively associated with three intervals (primary care interval, diagnostic interval, and total interval; correlation coefficients -0.23 to -0.34; P < 0.05). Higher education, age, and comorbidity levels were associated with shorter patient and diagnostic intervals. CONCLUSIONS: HL may be a potential target to improve timeliness of HNC diagnosis and reduce disparities in outcomes.

When should patients with T1N0 oral squamous cell carcinoma be considered for elective neck dissection?

AIMS: To identify adverse pathological features (APF) predicting nodal failure in clinically node negative T1 oral squamous cell carcinoma (OSCC). METHODOLOGY: This study evaluated patients with T1N0 (≤5 mm depth of invasion (DOI) and ≤2 cm diameter) oral cancers from a prospectively maintained database between 1988 and 2020. All patients underwent surgical excision of the primary lesion without neck dissection. Patients underwent three monthly clinical surveillance and salvage neck dissection was performed if nodal relapse was diagnosed. RESULTS: Overall, 141 patients were included. Nodal relapse was reported in 16/141 (11.3%) patients. Factors impacting regional recurrence-free survival were DOI ≥3 mm (HR: 2.4, P < 0.001), maximum tumour diameter ≥12 mm (HR: 1.1, P = 0.009), perineural invasion (PNI) (HR 7.5, P = 0.002) and poor differentiation (HR 5.3, P = 0.01). Rates of nodal relapse increased from 2% amongst patients with no APFs to 100% for those with four APFs. Patients with two or more APFs had significantly poorer 5-year regional recurrence-free survival (94.8% vs. 56.3%, P < 0.001). CONCLUSION: Patients with T1N0 OSCC with two or more APFs (DOI ≥3 mm, diameter ≥12 mm, PNI or poor differentiations) should be considered for elective neck dissection.

Patient-reported experiences and satisfaction with head and neck surgery outreach clinics in regional New South Wales, Australia: A cross-sectional survey.

RATIONALE: Head and neck surgery services are increasingly being centralised in Australia. Outreach models can overcome burdens of travel that patients in regional and rural areas experience when attending routine appointments, by providing services closer to home. AIM: To explore patient-reported experiences and satisfaction with regional outreach services for head and neck surgery in Australia. METHODS: Patients who attended two regional outreach clinics in New South Wales (NSW), Australia, were surveyed over a 6-month period. Patients completed the Outpatient Cancer Clinics Survey (2020 version) that explored perceptions and experiences of the clinic. Patients with cancer were asked to complete the Edmonton Symptom Assessment System and the Communication and Attitudinal Self-Efficacy scale. Descriptive statistics and analysis of data was performed, and results were compared to the NSW statewide Outpatient Cancer Clinics Survey (2020). Content analysis of free text responses was performed. RESULTS: Some 128 patients responded (56% response rate; mean age 67.2 years, 46.1% female). Compared to the 2020 NSW survey, a higher proportion of patients in our cohort responded positively to 14 of the 26 questions, with the greatest differences observed for questions regarding waiting area comfort (+12.1%, p = 0.008), being informed about different treatment options (+9.5%, p = 0.04), and issues relating to parking (+9.5%, p = 0.03). A lower proportion of our sample responded positively to the question about whether health professionals knew enough about their medical history (-19.3%, p < 0.001). Respondents appreciated having a local clinic that helped them avoid travel to major cities and associated expenses and highlighted benefits of expert consultation and timeliness of investigations. However, cost of appointments and level of reimbursements remain barriers for some patients. CONCLUSIONS: Patients had a high level of satisfaction with regional outreach clinics for head and neck surgery across most domains, indicating patients highly value this service.

ADMANI: Annotated Digital Mammograms and Associated Non-Image Datasets.

Supplemental material is available for this article. Keywords: Mammography, Screening, Convolutional Neural Network (CNN) Published under a CC BY 4.0 license. See also the commentary by Cadrin-Chênevert in this issue.

The Utility of Near-Infrared Autofluorescence for Parathyroid Gland Identification During Thyroid Surgery: A Single-Center Experience.

Parathyroid gland injury during thyroid surgery is common and can lead to postoperative hypocalcemia. This study aims to determine the utility of near-infrared autofluorescence (NIRAF) technology for parathyroid gland identification in thyroid surgery. A prospective case series of patients who underwent thyroid surgery between March and June 2021 were examined. Following intra-operative visualisation, parathyroid glands and surrounding tissues were exposed to near-infrared light with a wavelength of approximately 800 nm using the Storz® Near-Infrared Range/Indocyanine Green (NIR/ICG) endoscopic system. Parathyroid glands were expected to show autofluorescence following exposure. Twenty patients who underwent thyroid surgery were included. Eighteen patients (90%) were female, with a median age of 50.0 (IQR 41.0 - 62.5). Surgeries performed include hemithyroidectomy (9 patients; 45.0%), total thyroidectomy (8 patients; 40.0%), completion thyroidectomy (2 patients; 10.0%) and right inferior parathyroidectomy (1 patient; 5.0%). Attempts were made to identify 56 parathyroid glands in this case series. There were 46/56 (82.1%) surgeon-identified parathyroid glands through direct visualisation. Using NIRAF technology, 39/46 (84.8%) were identified as parathyroid glands. There was no inadvertent resection of parathyroid glands or post-operative hypocalcaemia. NIRAF technology has the potential to be a useful tool in confirming the presence of parathyroid glands following direct visualisation intra-operatively.

Comparative analysis of pre-operative ultrasound and histopathology in small papillary thyroid carcinoma in the era of active surveillance.

BACKGROUND: Contemporary management of small papillary thyroid carcinomas (PTC) includes active surveillance (AS) as a number of these tumours are indolent. Overseas studies have reported AS in tumours up to 15 mm. This study aims to look at an Australian cohort of patients who have had surgery for non-incidental PTCs and analyse their pre-operative ultrasound and histopathology data to investigate potential issues that might arise in the era of AS. METHODS: Retrospective review of 82 patients who had surgical removal of PTCs ≤15 mm in diameter. Pre-operative ultrasound imaging was reviewed by an experienced sonologist and histopathology data was obtained from medical records. The AS risk stratification framework by Brito et al. was used to determine those who were feasible for AS based on ultrasound findings. RESULTS: Review of pre-operative ultrasounds demonstrated there were 68 (82.9%) patients who were shown to be either appropriate or ideal for AS. On review of histopathology, 49 (69%) patients had at least one adverse pathological risk factor. This is more than half of the patients that were originally identified as candidates for AS. CONCLUSION: Our study has revealed a large proportion were suitable for AS but when compared with histopathological guidelines there was a high incidence of adverse pathological features found. This discrepancy indicates that although the guidelines are important, there are unknown pathological variables that need to be considered in patients selected for AS.

Anterolateral thigh, radial forearm and superficial circumflex iliac perforator flaps in oral reconstruction: a comparative analysis.

BACKGROUND: Anterolateral thigh (ALT) and Radial forearm free flaps (RFFF) are historically the most common methods of oral reconstruction. The Superficial circumflex iliac artery perforator flap (SCIP) is an alternative providing a donor site that can be readily closed primarily with improved cosmesis in younger patients, due to its concealability. METHODS: We reviewed 135 patients who received ALT, RFFF or SCIP flaps for oral reconstruction in our institution. Our aim was to compare operative and perioperative outcomes between each cohort. ANOVA and χ2 test were used for statistical analysis. RESULTS: There were 37 ALT, 64 RFFF and 35 SCIP reconstructions. Patients reconstructed with SCIP flaps had smaller resection volumes (P < 0.001) and earlier T and N classifications (P = 0.001, P = 0.008), and consequently reduced tracheostomy rates (P < 0.001), reduced need for enteral feeding at discharge (P < 0.001) and shorter length of stay and perioperative times (P < 0.001). SCIP flaps were more common in younger patients (P < 0.01). ALT flaps were used for more advanced disease (P = 0.001) and had larger resection volumes (P < 0.001) and increased need for assisted enteral feeding (P < 0.001). There were no significant differences in flap or donor site outcomes. There were two flap failures, both RFFF. CONCLUSION: Each flap plays an important role in the reconstruction of oral defects, with larger defects preferentially reconstructed with ALT flaps. SCIP appears to be a reliable alternative in small defects with excellent perioperative and postoperative outcomes.

Survival outcomes of perineural spread in head and neck cutaneous squamous cell carcinoma.

AIM: To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS). METHOD: Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high-volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco-regional failure and survival data were obtained. RESULTS: Forty-five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43-90). Median follow-up was 16.1 months (range 1-107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71-5.38), median disease-specific survival 5.1 years (95% CI 4.21-5.97) and median disease-free survival (DFS) was 1.7 years (95% CI 1.11-2.22). The estimated 5-year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29-2.22, P = 0.664). CONCLUSION: The likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery.

Recursive Partitioning to Determine Order of Significance of Regional Metastasis Characteristics in Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.

Benchmarking Survival Outcomes Following Surgical Management of pT3 and pT4 Cutaneous Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND: pT3/4 head and neck cutaneous squamous cell carcinomas (HNcSCCs) are associated with poor outcomes, including local recurrence, metastasis and death. Whilst surgery remains the standard treatment for advanced HNcSCC, novel systemic therapies, such as immunotherapy, are being used earlier in the treatment paradigm. It is imperative that the clinical outcomes of surgery are clearly described so that conventional and emerging treatment modalities can be better integrated and sequenced in the management of pT3/4 HNcSCC. METHODS: Patients with confirmed pT3/4 HNcSCC undergoing curative surgical resection between 2014-2020 were identified retrospectively from a prospectively maintained research database. The primary outcomes of interest were locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS). The secondary outcome was surgical complication rate. RESULTS: A total of 104 patients (median age 74, range 41-94 years) were included, 90% of which had pT3 tumors; 36.5% received adjuvant radiotherapy. Median follow-up was 24.3 (range 1.0-84.3) months. LRC at 5 years was 62.0%, DSS at 5 years was 83.7%, and OS at 5 years was 71.9%. Median time to recurrence was 8.4 months. LRC was reduced in the presence of margin involvement and previous treatment (radiotherapy/surgery). The major surgical complication rate was 9.6%. CONCLUSIONS: More than 60% of patients treated surgically for pT3/4 head and neck cSCC were alive and free of disease at 5 years posttreatment. High-risk features such as margin involvement and having had previous treatment (radiotherapy/surgery) should be used to guide adjuvant therapy.

A self-driving laboratory advances the Pareto front for material properties.

Useful materials must satisfy multiple objectives, where the optimization of one objective is often at the expense of another. The Pareto front reports the optimal trade-offs between these conflicting objectives. Here we use a self-driving laboratory, Ada, to define the Pareto front of conductivities and processing temperatures for palladium films formed by combustion synthesis. Ada discovers new synthesis conditions that yield metallic films at lower processing temperatures (below 200 °C) relative to the prior art for this technique (250 °C). This temperature difference makes possible the coating of different commodity plastic materials (e.g., Nafion, polyethersulfone). These combustion synthesis conditions enable us to to spray coat uniform palladium films with moderate conductivity (1.1 × 105 S m-1) at 191 °C. Spray coating at 226 °C yields films with conductivities (2.0 × 106 S m-1) comparable to those of sputtered films (2.0 to 5.8 × 106 S m-1). This work shows how a self-driving laboratoy can discover materials that provide optimal trade-offs between conflicting objectives.

Application of salivary noncoding microRNAs for the diagnosis of oral cancers.

Oral cancer is on the rise globally and survival rates, despite improvements in clinical care, have not significantly improved. Early detection followed by immediate intervention is key to improving patient outcomes. The use of biomarkers has changed the diagnostic landscape for many cancers. For oral cancers, visual inspection followed by a tissue biopsy is standard practice. The discovery of microRNAs as potential biomarkers has attracted clinical interest but several challenges remain. These microRNAs can be found in bodily fluids such as blood and saliva which have been investigated as potential sources of biomarker discovery. As oral cancer is localized within the oral cavity, saliva may contain clinically relevant molecular markers for disease detection. Our review provides an outline of the current advances for the application of salivary microRNAs in oral cancer. We also provide a technical guide for the processing of salivary RNAs to ensure accurate clinical measurement and validation.

Retina Injury After Dexamethasone Injection Into a Vitrectomized Eye.

Purpose: This work reports a case of retinal and vitreous hemorrhage after a dexamethasone (Ozurdex, Allergan) intravitreal implant injection to treat clinically significant macular edema (ME) in a patient with moderate nonproliferative diabetic retinopathy. Methods: A 61-year-old woman who had a vitrectomy 3 years prior in the right eye underwent intravitreal dexamethasone implant injection in the right eye. Immediately after the injection, the patient noted numerous floaters, with visual acuity decline from 20/30 before injection, to counting fingers at 3 feet after injection. Dilated examination revealed the dexamethasone implant resting against the retina, just inferior to the inferior arcade. On 360° fundus examination, the retina was found to be flat and attached. Optical coherence tomography of the macula demonstrated that the dexamethasone implant was preretinal, possibly having lifted the internal limiting membrane. Results: Thirty minutes after the injection, the patient reported that her vision was starting to clear. The patient was informed about what had transpired and warned about signs and symptoms of retinal detachment. She canceled her 1-week follow-up appointment because her vision returned to baseline. By 4 weeks post injection, her vision was 20/20 without macular edema. Conclusions: This case represents the first reported instance in which retinal impact by an Ozurdex implant was observed without treatment and vision recovered to baseline.

Acetazolamide: A New Treatment for Visual Vertigo.

Visual vertigo is a disorder characterised by symptoms of dizziness, vertigo, unsteadiness, disorientation, and general discomfort induced by visual triggers. It is currently treated with vestibular rehabilitation therapy, with no effective pharmacotherapy available for treatment-resistant cases. The objective of this study was to evaluate the efficacy of oral acetazolamide in improving symptoms of visual vertigo. A comparative case series of adult patients clinically diagnosed with visual vertigo was conducted from January 1992 to May 2015. Patients without a full neurologic or otorhinolaryngologic work-up, negative magnetic resonance imaging (MRI), and an organic cause for their symptoms were excluded. The identified patients were then contacted by phone to complete a voluntary symptom survey. Main outcome was the subjective reported percentage in symptom improvement. Secondary outcomes were subjective improvement by symptom triggers. The participants were retrospectively divided into three groups based on their treatment with acetazolamide: currently on acetazolamide, terminated acetazolamide, or never initiated acetazolamide. Fifty-seven patients met the inclusion criteria and were willing to complete the phone survey (19 currently on acetazolamide, 27 terminated acetazolamide, and 11 never initiated therapy). Overall symptomatic improvement was reported by 18 (94.7%) patients currently on acetazolamide, 18 (66.7 %) who terminated acetazolamide, and 5 (45.5%) who never initiated therapy, varying significantly by group (p = 0.0061). Greatest improvement was reported in symptoms triggered by being a passenger in a car. These results show that acetazolamide has a positive association with improvement of symptoms of visual vertigo.

Prognostic implications of lymph node yield and lymph node ratio in papillary thyroid carcinoma.

BACKGROUND: The lymph node yield (LNY) and the lymph node ratio (LNR) have been shown to be important prognostic factors in oral, colon, and gastric cancers. The role of the LNY and LNR in papillary thyroid cancer (PTC) is unclear. The aims of this study were to determine if a high LNR and a low LNY decrease disease-free survival rates. This study further aimed to determine an optimum nodal yield. METHODS: A retrospective analysis was conducted of 198 patients with PTC undergoing total thyroidectomy with neck dissection between 1987 and 2011. The LNY and LNR were adjusted by relevant covariates in a multivariate Cox regression analysis with Andersen-Gill extension. RESULTS: The LNR was associated with a decrease in disease-free survival (hazard ratio 3.2 [95% confidence interval 1.4-7.3], p=0.005). Patients with an LNR of 0.30 or higher had a 3.4 times higher risk of persistent or recurrent disease compared with patients with an LNR of 0.00 ([95% confidence interval 1.1-10.5], p=0.031). Conversely, patients with an LNR of 0.11 or lower had an 80% chance of remaining disease free during 5 years of follow-up. The LNY showed no significant independent effect and an optimum nodal yield was not determined. CONCLUSIONS: The LNR is an important independent prognostic factor in PTC and can be used in conjunction with existing staging systems. A clinical relevant cut-off point of 0.3 (one positive lymph node out of three total) is proposed. No prognostic implications for LNY were identified.

The prognostic and staging implications of bone invasion in oral squamous cell carcinoma.

BACKGROUND: A study was undertaken to determine whether bone invasion is an independent prognostic factor in oral squamous cell carcinoma (SCC) after taking into account the extent of bone invasion. METHODS: The study was a retrospective review of 498 patients with oral SCC undergoing surgery with curative intent, 102 of whom had pathologically proven bone invasion. Bone invasion was categorized as absent, cortical, or medullary and tested for association with disease control and survival. RESULTS: After adjusting for potential confounding factors in multivariate analysis, there was no association between cortical invasion and overall (P = .48) or disease-specific survival (P = .63). In contrast, medullary invasion was an independent predictor of reduced overall (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2-3.1; P = .006) and disease-specific survival (HR, 2.1; 95% CI, 1.2-3.6; P = .01), and this appeared to result from an increased risk of distant metastatic failure (P = .037) rather than local (P = .51) or regional recurrence (P = .14). Within the subset of patients with medullary invasion, survival differed significantly according to tumor size (P = .029). CONCLUSIONS: Patients with oral SCC and bone invasion have widely variable outcomes depending on the depth of bone invasion and tumor size. The results suggest that the current American Joint Committee on Cancer staging system, which classifies all tumors invading through cortical bone as T4, has limited prognostic utility. The authors recommend a revision of the T staging system such that tumors are classified as T1 to T3 based on size and then upstaged by 1 T stage in the presence of medullary bone invasion.

Role of thyroidectomy in advanced laryngeal and pharyngolaryngeal carcinoma.

OBJECTIVE: Total thyroidectomy (TThy) or hemithyroidectomy (HThy) in conjunction with a total laryngectomy (TL) or pharyngolaryngectomy (PL) for laryngeal carcinoma often results in hypothyroidism requiring life-long thyroid hormone replacement. The aims were to determine the incidence of thyroid gland (TG) invasion in patients undergoing TL or TPL with TThy or HThy for laryngeal or hypopharyngeal carcinoma and to assess predicative factors. STUDY DESIGN: Case series with chart review. SETTING: Guy's Hospital, London, UK. SUBJECTS AND METHODS: Thirty-five patients from 2004 to 2008 were reviewed. Specimens were examined to determine the incidence of TG invasion and predicative factors. Preoperative imaging was reviewed to assess the radiological evidence of TG invasion. RESULTS: TL and TThy were performed in 19 patients, TL and HThy in three patients, and PL and TThy in 13 patients. Surgery was performed for primary and recurrent carcinoma in 28 and eight patients, respectively. Histological evidence of invasion of the TG was found in three patients (8.5%). No significant relationship was found between TG invasion and patient's sex, subsite of primary carcinoma, stage of primary disease at surgery, degree of differentiation, or the presence of subglottic extension. In addition, no significant relationship was found between the presence of TG invasion and recurrent disease. Definite evidence of radiological invasion of the TG was seen in only one patient. CONCLUSIONS: Invasion of the TG in patients undergoing TL or TPL is a rare event and limits the need for TThy in most cases.