National Improvement of Waiting Times: First Results From the Dutch Head and Neck Audit.

OBJECTIVE: Timely treatment initiation in head and neck cancer (HNC) care is of great importance regarding survival, oncological, functional, and psychological outcomes. Therefore, waiting times are assessed in the Dutch Head and Neck Audit (DHNA). This audit aims to assess and improve the quality of care through feedback and benchmarking. For this study, we examined how waiting times evolved since the start of the DHNA. STUDY DESIGN: Prospective cohort study. SETTING: National multicentre study. METHODS: The DHNA was established in 2014 and reached national coverage of all patients treated for primary HNC in 2019. DHNA data on curative patients from 2015 to 2021 was extracted on national (benchmark) and hospital level. We determined 3 measures for waiting time: (1) the care pathway interval (CPI, first visit to start treatment), (2) the time to treatment interval (TTI, biopsy to start treatment), and (3) CPI-/TTI-indicators (percentage of patients starting treatment ≤30 days). The Dutch national quality norm for the CPI-indicator is 80%. RESULTS: The benchmark median CPI and TTI improved between 2015 and 2021 from 37 to 26 days and 37 to 33 days, respectively. Correspondingly, the CPI- and TTI-indicators, respectively, increased from 39% to 64% and 35% to 40% in 2015 to 2021. Outcomes for all hospitals improved and dispersion between hospitals declined. Four hospitals exceeded the 80% quality norm in 2021. CONCLUSION: Waiting times improved gradually over time, with 4 hospitals exceeding the quality standard in 2021. On the hospital-level, process improvement plans have been initiated. Systematic registration, auditing, and feedback of data support the improvement of quality of care.

Spatial Transcriptomic Technologies.

Spatial transcriptomic technologies enable measurement of expression levels of genes systematically throughout tissue space, deepening our understanding of cellular organizations and interactions within tissues as well as illuminating biological insights in neuroscience, developmental biology and a range of diseases, including cancer. A variety of spatial technologies have been developed and/or commercialized, differing in spatial resolution, sensitivity, multiplexing capability, throughput and coverage. In this paper, we review key enabling spatial transcriptomic technologies and their applications as well as the perspective of the techniques and new emerging technologies that are developed to address current limitations of spatial methodologies. In addition, we describe how spatial transcriptomics data can be integrated with other omics modalities, complementing other methods in deciphering cellar interactions and phenotypes within tissues as well as providing novel insight into tissue organization.

Intratumoral Niches of B Cells and Follicular Helper T Cells, and the Absence of Regulatory T Cells, Associate with Longer Survival in Early-Stage Oral Tongue Cancer Patients.

In early oral squamous cell carcinoma (OSCC), the occurrence of clusters between CD20 B cells and CD4 T cells in the invasive margin (IM) can be captured by using the CD20 cluster score, and is positively associated with patient survival. However, the exact contribution of different CD4 T cell subsets, as well as B cell subsets toward patient prognosis is largely unknown. To this end, we studied regulatory T cells ((Treg cells) FOXP3 and CD4), T helper-type 1 cells ((Th1 cells) Tbet and CD4), follicular helper T cells ((Tfh cells) Bcl6 and CD4), B cells (CD20), germinal center B cells ((GC B cells) BCL6 and CD20), and follicular dendritic cells ((fDCs) CD21) for their density, location, and interspacing using multiplex in situ immunofluorescence of 75 treatment-naïve, primary OSCC patients. We observed that Treg, Th1-, Tfh-, and GC B cells, but not fDCs, were abundantly present in the stroma as compared with the tumor, and in the IM as compared with in the center of the tumor. Patients with high CD20 cluster scores had a high density of all three CD4 T cell subsets and GC B cells in the stromal IM as compared with patients with low CD20 cluster scores. Notably, enriched abundance of Tfh cells (HR 0.20, p = 0.04), and diminished abundance of Treg cells (HR 0.10, p = 0.03), together with an overall short distance between Tfh and B cells (HR:0.08, p < 0.01), but not between Treg and B cells (HR 0.43, p = 0.28), were significantly associated with overall survival of patients with OSCC. Our study identified the prognostic value of clusters between CD20 B cells and Tfh cells in the stromal IM of OSCC patients, and enabled an improved understanding of the clinical value of a high CD20 cluster score, which requires validation in larger clinical cohorts.

Linking the genotypes and phenotypes of cancer cells in heterogenous populations via real-time optical tagging and image analysis.

Linking single-cell genomic or transcriptomic profiles to functional cellular characteristics, in particular time-varying phenotypic changes, could help unravel molecular mechanisms driving the growth of tumour-cell subpopulations. Here we show that a custom-built optical microscope with an ultrawide field of view, fast automated image analysis and a dye activatable by visible light enables the screening and selective photolabelling of cells of interest in large heterogeneous cell populations on the basis of specific functional cellular dynamics, such as fast migration, morphological variation, small-molecule uptake or cell division. Combining such functional single-cell selection with single-cell RNA sequencing allowed us to (1) functionally annotate the transcriptomic profiles of fast-migrating and spindle-shaped MCF10A cells, of fast-migrating MDA-MB-231 cells and of patient-derived head-and-neck squamous carcinoma cells, and (2) identify critical genes and pathways driving aggressive migration and mesenchymal-like morphology in these cells. Functional single-cell selection upstream of single-cell sequencing does not depend on molecular biomarkers, allows for the enrichment of sparse subpopulations of cells, and can facilitate the identification and understanding of the molecular mechanisms underlying functional phenotypes.

Surgical management of inverted papilloma; a single-center analysis of 247 patients with long follow-up.

BACKGROUND: Our aim was to review our management of inverted papilloma (IP), perform a recurrence analysis, and review the literature. METHODS: A retrospective analysis of 247 patients treated for an IP. Patients were grouped according to surgical approach, tumor presentation (primary, residual and recurrence) and Krouse-stage. RESULTS: Recurrence was observed in 20.3%, 28.6% and 35.1% (p = 0.017) of the patients who underwent endoscopic, external and combined surgery, respectively. Recurrences occurred more often in residual than primary IP (36.9% vs. 22.3%, p = 0.021). Primary endoscopic surgery had a recurrence rate of 12.5%, which was comparable to the recent literature (11.2%, 161/1433). CONCLUSIONS: The relatively high number of recurrences in this cohort is explained by the long follow-up and previous (incomplete) surgery in 61.5% of the cases. The inferior outcome of residual IP underscores the importance of having a low threshold for preoperative biopsy in unilateral and atypical sinonasal disease.

Denker operation is an effective surgical approach in managing juvenile nasopharyngeal angiofibroma.

This article presents our experience with the various surgical approaches for angiofibroma and establishes the Denker procedure as an effective approach for removal of the tumor. The medical records of 29 patients treated between the years 1981 and 2001 were examined. The clinical extent of the tumor, the surgical approach, complications, and recurrences were evaluated. The surgical approaches used before 1992 consisted of the transnasal, transpalatal, and combined transnasal-transpalatal ones. Although no major recurrence or major morbidity was observed, late complications occurred, such as persistent palatal fistula in 3 patients who underwent operation via a transpalatal approach, and an unsightly scar with lacrimal duct stenosis in 2 patients who underwent operation via a combined transnasal-transpalatal approach. From 1992 onward, the above-mentioned surgical approaches were replaced with the Denker and midfacial degloving techniques, which proved to be just as effective in removing the tumor and did not produce late complications. According to our experience, the Denker approach is effective for angiofibromas confined to the nasal cavity and nasopharynx with small extensions in the infratemporal fossa. On the other hand, large tumor extension in the infratemporal fossa can be effectively approached in combination with a midfacial degloving technique.