Treatment and Prognosis of Inflammatory Pseudotumor of the Skull Base.

Background Inflammatory pseudotumor (IPT) of the skull base is a rare, locally destructive lesion managed with a variety of treatments. We explore the impact of treatment on outcome and assess the prognosis of IPT. Methods This is a retrospective review of IPT of the skull base at a tertiary academic medical center. The primary outcome was radiographic progression after treatment. Outcome versus tumor location was also examined and a prognostic model was developed using a logistic regression. Results The demographics of 21 patients with IPT are reported. Treatment consisted of corticosteroids (in 80.1% of patients), disease modifying antirheumatic drugs (DMARDs; 33.3%), surgical resection (28.6%), radiation (23.8%), antibiotics (14.3%), chemotherapy (rituximab; 9.5%), and antivirals (4.8%). At 50.7 months, 50.8% had radiographic progression. Local therapy trended toward having a better response than systemic therapy ( p = 0.60). IPT of the orbit required 2.4 treatment modalities, compared with 2.0 for pharyngeal IPT, and 1.3 for posterior skull base masses ( p = 0.14). A total of 75% orbital IPT underwent radiographic progression, compared with 71% of pharyngeal IPT and 50% of posterior skull base masses ( p = 0.62). Sixteen patients were used to create the logistic model of radiographic progression. The Cox-Snell R 2 was 0.71 ( p = 0.03). No individual variables were statistically significant. Conclusion To our knowledge, this is among the largest sample of cases describing the presentation, treatment, and prognosis of IPT of the skull base. Our data suggest that there may be an improved response with local therapy over systemic therapy and better prognosis among posterolateral skull base masses.

To Pack a Nose: High-Fidelity Epistaxis Simulation Using 3D Printing Technology.

BACKGROUND: Initial management and stabilization of epistaxis is managed by a diverse offset of clinical providers with variable levels of training. OBJECTIVE: To determine the anatomic and clinical fidelity and ease of use of a novel simulator for the training and assessment of epistaxis management skills. STUDY DESIGN: Qualitative Research Study using expert questionnaire's for validation of a newly developed simulator. METHODS: We performed a quasi-experimental intervention with 22 otolaryngology faculty and 10 trainees who independently evaluated the simulator. Data were collected in three phases: phase 1 (preliminary evaluation), phase 2 (final expert evaluation), and phase 3 (trainee evaluation). We designed a three-dimensional (3D) printed model from a de-identified patient computed tomography scan. Artificial blood was circulated through catheters to simulate bleeding from three distinct sites (sphenopalatine, Kiesselbach's plexus, and anterior ethmoid). Four domains were assessed: "Physical and anatomic attributes," "Realism of experience," "Ability to perform tasks," and "Value and clinical relevance." Internal structure and validity were measured with Cronbach's alpha and item outfit mean-square statistics. RESULTS: Results from otolaryngology faculty showed very high median ratings for "Value of the simulator as a training tool" (4.0/4) and high ratings for "Relevance to practice" (4.0/4), and realism of experience (4.0/4). Responses from otolaryngology trainees demonstrated high value for clinical training (4.0/4) and high likelihood to recommend use for future trainees (4.0/4). Confidence in managing epistaxis before (1.0/4) and after (3.0/4) simulator use was statistically improved (P = .03). CONCLUSIONS: Using 3D printing technology, we created a novel simulator for epistaxis management. Preliminary evidence suggests the model is cost-effective, anatomically realistic, relevant to trainees' educational needs, and valuable as a training tool. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:747-753, 2022.

Head and Neck Cancer and Social Media: The Patient Experience and Cancer Survivorship.

OBJECTIVES/HYPOTHESIS: To characterize the head and neck cancer patients' lived experiences with survivorship through Instagram and examine opportunities for health professionals to provide support and outreach specifically targeting these needs. STUDY DESIGN: Descriptive observational study. METHODS: We analyzed key head and neck cancer-related hashtags by querying medical and layman terminology. The top English-language posts for #headandneckcancer underwent further content examination using thematic analysis based in grounded theory for categorization for user engagement (determined by "likes" and comments), type of content, and category of the account that created the post. Of the survivorship posts by patients, the content of posts in top user accounts was further analyzed. RESULTS: There were 11,600 Instagram posts on #headandneckcancer, 1,300 posts on #headandneckcancerawareness, 1,100 posts on #headandneckcancersurvivor, and several thousand posts for additional layman terms. The majority of posts were from patients (65%), with few from head and neck surgeons or medical organizations (26%). User engagement was primarily by nonmedical accounts (95%). Posts by patients discussed medical appointments and treatments (81%), managing treatment effects and symptoms (66%), and cancer screening and prevention (23%). Specific concerns included fatigue (53%), postsurgical cosmetic appearance (27%), and weight and nutrition (34%). CONCLUSIONS: Our study suggests that Instagram accounts can be intimate records of the patient experience, and gaining a better understanding of the daily experience of survivorship may be critical for head and neck surgeons and other oncology providers to provide truly comprehensive cancer care. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1214-E1219, 2021.

A 3D-printed Lateral Skull Base Implant for Repair of Tegmen Defects: A Case Series.

OBJECTIVE: To determine the feasibility of a patient-specific, three-dimensionally (3D)-printed reconstruction plate for repair of lateral skull base defects. STUDY DESIGN: Prospective case series and cadaveric study. SETTING: A university-based, tertiary care hospital. PATIENTS: Three patients with lateral skull base defects and five cadavers. MAIN OUTCOME MEASURE(S): Caliper gauge fit testing was performed in the cadaver temporal bones to determine the fit of the tegmen plate in engaging the tegmen defect. Additionally, three patients underwent standard of care reconstruction of their middle fossa floor using autografts or allografts. Temporary plate insertion during standard operative repair was performed to gauge feasibility and fit. Operative time required for standard grafting compared with placement of the tegmen plate was examined. RESULTS: Real-time, intraoperative placement of the tegmen plate in our patients under 1 minute compared with nearly 60 minutes for standard surgical repair. Tegmen plates covered the defects and locked into place from contour matching without impinging on critical structures. Fit testing revealed flush-fitting plates to the cadaveric temporal bone surface with all gaps less than 500 µm. CONCLUSIONS: Computer modeling and 3D printing can design custom fitted tegmen reconstruction plates for temporal bone defects. Versatility in prefabrication and 3D modeling shows potential in allowing the construct to avoid critical structures and adequately cover defects with high precision to the tegmen surface.

Impact of a deep learning assistant on the histopathologic classification of liver cancer.

Artificial intelligence (AI) algorithms continue to rival human performance on a variety of clinical tasks, while their actual impact on human diagnosticians, when incorporated into clinical workflows, remains relatively unexplored. In this study, we developed a deep learning-based assistant to help pathologists differentiate between two subtypes of primary liver cancer, hepatocellular carcinoma and cholangiocarcinoma, on hematoxylin and eosin-stained whole-slide images (WSI), and evaluated its effect on the diagnostic performance of 11 pathologists with varying levels of expertise. Our model achieved accuracies of 0.885 on a validation set of 26 WSI, and 0.842 on an independent test set of 80 WSI. Although use of the assistant did not change the mean accuracy of the 11 pathologists (p = 0.184, OR = 1.281), it significantly improved the accuracy (p = 0.045, OR = 1.499) of a subset of nine pathologists who fell within well-defined experience levels (GI subspecialists, non-GI subspecialists, and trainees). In the assisted state, model accuracy significantly impacted the diagnostic decisions of all 11 pathologists. As expected, when the model's prediction was correct, assistance significantly improved accuracy (p = 0.000, OR = 4.289), whereas when the model's prediction was incorrect, assistance significantly decreased accuracy (p = 0.000, OR = 0.253), with both effects holding across all pathologist experience levels and case difficulty levels. Our results highlight the challenges of translating AI models into the clinical setting, and emphasize the importance of taking into account potential unintended negative consequences of model assistance when designing and testing medical AI-assistance tools.

Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers.

PURPOSE: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. EXPERIMENTAL DESIGN: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery. RESULTS: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery. CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.

Effect of Medical Scribes on Outpatient Oncology Visits at a Multidisciplinary Cancer Center.

PURPOSE: The use of medical scribes has emerged as a strategy to increase clinic workflow efficiency and reduce physician burnout. While oncology clinics may be ideally suited to scribe integration because of the high burden of documentation, oncology-specific scribe research has been limited. The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics. METHODS: We conducted a retrospective, concurrent qualitative and quantitative analysis of patient visit durations and survey data for 129 attending physicians affiliated with an academic hospital's cancer center between January 2017 and January 2019. Thirty-three physicians were paired with scribes in each physician's individual clinic or clinics. RESULTS: In terms of clinic efficiency, physicians with scribes had a 12.1% decrease in their overall average patient visit duration compared with their own time before receiving a scribe (P < .0001) and spent significantly less time completing charts at the end of the day (P = .04). Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits. Scribes also contributed to patient care, as shown by 90% of physicians surveyed who strongly agreed that they spent less time at the computer and more time with patients; 100% of physicians surveyed strongly agreed that scribes improved their quality of life. CONCLUSION: The integration of medical scribes into oncology clinics across several oncologic disciplines has the potential to reduce burnout through increasing physician satisfaction and quality of life, improving patient care, and streamlining clinic workflow.

Outcomes in Head and Neck Resections That Require Multiple-Flap Reconstructions: A Systematic Review.

Importance: Complex head and neck cancer defects that require multiflap reconstructions are technically feasible, but the morbidity and patient outcomes of such large-scale head and neck operations have yet to be systematically reviewed. Objective: To systematically review existing literature to characterize the outcomes of large-scale head and neck resections that require multiple-flap reconstructions (defined as defects that require >1 flap [free, pedicled, or combinations thereof]). Evidence Review: Two authors independently searched PubMed, Embase, and the Cochrane Review databases for English-only texts published on any date. Included studies examined patients who underwent complex head and neck surgical resections that required multiple simultaneous flaps for reconstruction. Included studies reported results on at least one of the following outcomes: functional and aesthetic, patient survival, or cost (estimated by operating room time, length of stay, and/or complications). Methodological Index for Non-Randomized Studies (MINORS) criteria for bias and modified Oxford Centre for Evidence-Based Medicine recommendations were used to assess study quality. Findings: Twenty-four studies published from November 1, 1992, through September 1, 2016, met the final inclusion criteria, with a total of 487 patients (370 male [79.4%]; mean [SD] weighted age, 55.1 [4.1] years). Sixty-two of 250 patients (24.8%) were partially or fully dependent on feeding tubes at follow-up. Twenty-two of 75 patients (29.3%) had poor postoperative oral competence, causing moderate to severe drooling. Nineteen of 108 patients (17.6%) had unintelligible speech. Nine of 64 patients (14.1%) were unsatisfied with their aesthetic outcome. The mean (SD) reported survival was 2.36 (1.39) years. The mean (SD) length of stay was 24.5 (12.2) days in 219 patients. Eighty-eight minor complications (eg, partial flap necrosis, donor site complications) and 185 major complications (eg, surgical reexplorations, flap loss, or cardiopulmonary complications) were reported in 380 patients. Mean (SD) MINORS scores were 16.0 (3.2) for comparison studies and 11.4 (1.8) for noncomparison studies. Conclusions and Relevance: Because of limited patient life expectancies, modest functional and aesthetic outcomes, and significant associated costs, surgeons should weigh the curative potential and palliative benefits for individual patients with a comprehensive view of the overall outcomes of extensive head and neck resections and reconstructions. Realistic expectations should be emphasized during preoperative discussions with patients.

Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence.

For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. Twenty-one adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n = 3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n = 5) received 0.5 mg/kg, cohort 2B (n = 7) received 1 mg/kg, and cohort 3 (n = 6) received 50 mg. Patients were followed 30 days postinfusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2 to 3, compared with ex vivo specimen imaging TBR of 5 to 6. We obtained clear differentiation between tumor and normal tissue, with a 3-fold signal difference between positive and negative specimens (P < 0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy, which are otherwise less amenable to image guidance.Significance: This study demonstrates that fluorescence can be used as a sensitive and specific method of guiding surgeries for head and neck cancers and potentially other cancers with challenging imaging conditions, increasing the probability of complete resections and improving oncologic outcomes. Cancer Res; 78(17); 5144-54. ©2018 AACR.

Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers.

Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.

Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival.

BACKGROUND: While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas. PATIENTS AND METHODS: The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses. RESULTS: A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01). CONCLUSION: Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies.

Survival and risk factors for progression after resection of the dominant tumor in multifocal, lepidic-type pulmonary adenocarcinoma.

BACKGROUND: It remains unclear whether a dominant lung adenocarcinoma that presents with multifocal ground glass opacities (GGOs) should be treated by local therapy. We sought to address survival in this setting and to identify risk factors for progression of unresected GGOs. METHODS: Retrospective review of 70 patients who underwent resection of a pN0, lepidic adenocarcinoma, who harbored at least 1 additional GGO. Features associated with GGO progression were determined using logistic regression and survival was evaluated using the Kaplan-Meier method. RESULTS: Subjects harbored 1 to 7 GGOs beyond their dominant tumor (DT). Mean follow-up was 4.1 ± 2.8 years. At least 1 GGO progressed after DT resection in 21 patients (30%). In 11 patients (15.7%), this progression prompted resection (n = 5) or stereotactic radiotherapy (n = 6) at mean 2.8 ± 2.3 years. Several measures of the overall tumor burden were associated with GGO progression (all P values < .03) and with progression prompting intervention (all P values < .01). In logistic regression, greater DT size (odds ratio, 1.07; 95% confidence interval, 1.01-1.14) and an initial GGO > 1 cm (odds ratio, 4.98; 95% confidence interval, 1.15-21.28) were the only factors independently associated with GGO progression. Survival was not negatively influenced by GGO progression (100% with vs 80.7% without; P = .1) or by progression-prompting intervention (P = .4). CONCLUSIONS: At 4.1-year mean follow-up, 15.7% of patients with unresected GGOs after resection of a pN0 DT underwent subsequent intervention for a progressing GGO. Some features correlated with GGO growth, but neither growth, nor need for an intervention, negatively influenced survival. Thus, even those at highest risk for GGO progression should not be denied resection of a DT.

Variegated expression of Hsp22 transgenic reporters indicates cell-specific patterns of aging in Drosophila oenocytes.

The cytoplasmic chaperone gene Hsp70 and the mitochondrial chaperone gene Hsp22 are upregulated during normal aging in Drosophila in tissue-general patterns. In addition, Hsp22 reporters are dramatically upregulated during aging in a subset of the oenocytes (liver-like cells). Hsp22 reporter expression varied dramatically between individual oenocytes and between groups of oenocytes located in adjacent body segments, and was negatively correlated with accumulation of age pigment, indicating cell-specific and cell-lineage-specific patterns of oenocyte aging. Conditional transgenic systems were used to express 88 transgenes to search for trans-regulators of the Hsp70 and Hsp22 reporters during aging. The wingless gene increased tissue-general upregulation of both Hsp70 and Hsp22 reporters. In contrast, the mitochondrial genes MnSOD and Hsp22 increased expression of Hsp22 reporters in the oenocytes and decreased accumulation of age pigment in these cells. The data suggest that cell-specific and cell lineage-specific patterns of mitochondrial malfunction contribute to oenocyte aging.