International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Projected cutting guides using an augmented reality system to improve surgical margins in maxillectomies: A preclinical study

Background: Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR. Methods: Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between “ideal” cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed. Results: 115 virtual osteotomies were analyzed. Intra-tumoral and “close” margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p < 0.0001 and 0.8% vs 7.9% p < 0.0001). Proportion of “adequate” margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in “adequate” margins 0.893 (95% CI: 0.804–0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration. Conclusion: The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes

Supplementary Methods from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

All supplementary methods.</p

FIGURE 3 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Pharmacokinetic profiles of PS nanoparticles in tumor-bearing mice and rabbit models of oral cavity cancer. Plasma concentration-time profiles of PS in Cal-33 and MOC22 mouse models (A) and VX-2 rabbit model (B). Units µg/mL. Additional pharmacokinetic analysis is detailed in Supplementary Table S2. Tissue concentrations of PS in Cal-33 and MOC22 mouse models (C) and VX-2 rabbit model (D) 24 hours post-injection. Units µg/g. Additional tissue distribution data are provided in Supplementary Tables S3–S5. Ratios of PS tissue concentration normalized to muscle concentration in Cal-33 and MOC22 mouse models (E) and VX-2 rabbit model (F) 24 hours post-injection. Unitless. Representative fluorescence images and ratios of PS ex vivo tissue fluorescence normalized to muscle fluorescence in Cal-33 and MOC22 mouse models (G), and VX-2 rabbit model (H) 24 hours postinjection. Unitless. Additional PS tissue selectivity data are provided in Supplementary Tables S6 and S7. For A, B, Mean ± SD. Table statistics: mean ± SE N = 5 mice/model. N = 6 rabbits. For C, D, E, and F, Tukey box-and-whisker plot with “+” denoting mean (mean value labeled above). N = 5 mice/tissue/model. N = 3 rabbits/tissue. For G and H, Bar plot with mean + SD (mean value labeled above). N = 5 mice/tissue/model. N = 3 rabbits/tissue. For G, Ex: 675 nm, Em: 720 nm, 1 second exposure time. For H, Ex: 675 nm, Em: 720 nm long pass. For mouse models: PS dose = 10 mg/kg, 400–500 MBq 64Cu/kg, i.v. For rabbit models: PS dose = 10 mg/kg, i.v.</p

FIGURE 2 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Photophysical and photochemical characterization of PS nanoparticles. A, Structure and composition of PS: PEGylated porphyrin-lipid conjugate-containing nanoparticles. B, Transmission electron microscopy of negatively stained PS nanoparticle morphology. Scale bar, 0.1 µm. C, Molar attenuation coefficient (ε) profile of intact and disassembled PS in aqueous media. Intact PS are suspended in 1x PBS and disassembled PS are treated with a non-ionic surfactant (Triton X-100). Note ε reported here on basis of mols of porphyrin-lipid conjugate. D, Fluorescence spectra of intact and disassembled PS nanoparticles in aqueous media at excitation wavelength 416 nm. Note the 100-fold increase in fluorescence intensity in the disassembled PS versus the intact PS at 675-nm wavelength. E, Singlet oxygen (1O2) generation of intact and disassembled PS nanoparticles in aqueous media with increasing light dose. Note the approximately 4-fold increase in 1O2 generation in the disassembled PS versus the intact PS using 671-nm excitation wavelength (50 mW). Mean ± SD. N = 5 samples/light dose. Additional material characterizations of PS described in Supplementary Fig. S1 and Supplementary Table S1.</p

Figure S2 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Supplementary figure 2 and legend.</p

Figure S3 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Supplementary figure 3.</p

FIGURE 6 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Antitumor treatment response to PS-PDT (10 mg/kg, 24 hour DLI, 200 J total) in an orthotopic VX-2 rabbit tumor model. A, Overview of “two-step” PDT treatment scheme in rabbits involving first, surface illumination of the tumor through the overlying skin using an external laser beam (100 J/cm2, 100 mW/cm2); and second, interstitial illumination with a diffusing fiber (1 cm, 100 J/cm, 100 mW/cm) inserted into the center of the tumor mass. B, Survival analysis of buccal VX-2 tumors following start of treatment on week 0. Event was tumor volume >3.05 cm3 (humane endpoint). N = 5 tumors (single PS-PDT), 4 tumors (repeat PS-PDT), 3 tumors (drug control), and 3 tumors (light control). Statistics: multiple comparisons of survival curves performed with log-rank tests using Bonferroni correction method for multiple comparison and ⍺ = 0.05. Single PS-PDT versus repeat PS-PDT = ns; Single PS-PDT versus drug control = ns; Single PS-PDT versus light control = *; Repeat PS-PDT versus drug control = *; Repeat PS-PDT versus light control = **. Fold change in tumor volume (C) and representative white light images and CT image reconstructions (D) of orthotopic buccal VX-2 tumors following single PS-PDT treatment on week 0. Fold change in tumor volume (E) and representative white light images and CT image reconstructions (F) following repeat PS-PDT treatments on weeks 0, 1, and 2. For C and E, red arrows indicated occasions of PS-PDT treatment. For D and F, normal anatomy outlined in purple, VX-2 tumor highlighted in green. Images not scaled for size. Additional PS-PDT efficacy data and statistical analysis are provided in Supplementary Table S11.</p

Figure S8 from Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

Supplementary figure 8 and legend.</p