Publications by authors named "Jose A U Hardillo"

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.

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Near-infrared (NIR) fluorescence imaging using exogenous fluorescent agents provides whole-field images in real-time to assist the surgeon in the excision of a tumor. Although the method has high sensitivity, the specificity can sometimes be lower than expected. Raman spectroscopy can detect tumors with high specificity.

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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.

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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.

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Introduction: A challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases.

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Article Synopsis
  • Laryngeal cancer is a common and serious type of cancer in the head and neck, often leading to low survival rates, especially in advanced stages.
  • Early-stage treatment typically involves surgery or radiotherapy, while advanced cases are managed with more complex therapies like chemoradiotherapy or laryngectomy, but recurrence rates remain high.
  • This review evaluates various intraoperative optical imaging techniques, noting that while tools like narrow-band imaging and autofluorescence help with early detection, they struggle with deeper tissue imaging and suggesting that newer methods could enhance surgical outcomes.
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Objectives: The guided self-help exercise program called In Tune without Cords (ITwC) is effective in improving swallowing problems and communication among patients treated with a total laryngectomy (TL). This study investigated the cost-utility and cost-effectiveness of ITwC.

Materials And Methods: Patients within 5 years after TL were included in this randomized controlled trial.

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Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the delineation of tumours. Currently, in phase 1 and 2 clinical trials, evaluation of fluorescence-guided surgery is primarily focused on its diagnostic performance, although the corresponding outcome variables do not inform about the added clinical benefit of fluorescence-guided surgery and are challenging to assess objectively. Nonetheless, the effect of fluorescence-guided surgery on intraoperative decision making is the most objective outcome measurement to assess the clinical value of this imaging method.

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Background: The aim of this study was to identify risk factors for the development of second primary tumors (SPTs) in the head and neck region, lungs, and esophagus in patients with head and neck cancer.

Methods: We collected data from 1581 patients. A cause-specific Cox model for the development of an SPT was fitted, accounting for the competing risks residual/recurrent tumor and mortality.

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Background: Head and Neck cancer (HNC) is characterized by significant mortality and morbidity. Treatment is often invasive and interferes with vital functions, resulting in a delicate balance between survival benefit and deterioration in quality of life (QoL). Therefore, including prognostic information during patient counseling can be of great importance.

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Objective: To investigate the effectiveness of a guided self-help exercise program on swallowing, speech, and shoulder problems in patients treated with total laryngectomy (TL).

Materials And Methods: This randomized controlled trial included patients treated with TL in the last 5 years. Patients were randomized into the intervention group (self-help exercise program with flexibility, range-of-motion and lymphedema exercises and self-care education program) or control group (self-care education program).

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Background: Fibrous dysplasia (FD) is most often a slowly progressive benign disease in which the normal bone structure is replaced by fibrous and osteoid tissue.

Case Description: A 16-year-old adolescent, known with FD in the sphenoid bone, suffered an acute decreased visual acuity with papilledema on the left eye. The radiologic images were best compatible with cystic degeneration of the known FD with optic nerve compression in the optic canal.

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Objectives/hypothesis: This study aimed to analyze the effect of human papillomavirus (HPV)-associated T1-2 node-positive oropharyngeal squamous cell carcinoma (OPSCC) on nodal response, recurrent disease, and survival in patients treated according to the Rotterdam protocol.

Study Design: Retrospective cohort study.

Methods: In total, 77 patients with T1-2 OPSCC with nodal disease, treated between 2000 and 2012, were included in this study.

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Background: Total laryngectomy with or without adjuvant (chemo)radiation often induces speech, swallowing and neck and shoulder problems. Speech, swallowing and shoulder exercises may prevent or diminish these problems. The aim of the present paper is to describe the study, which is designed to investigate the effectiveness and cost-utility of a guided self-help exercise program built into the application "In Tune without Cords" among patients treated with total laryngectomy.

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Objectives: To report oncologic outcomes of patients with paranasal sinus cancer (PNSC) treated by surgery and radiotherapy or (chemo)radiation and to investigate the impact of improving the radiation technique on outcomes and toxicity.

Materials And Methods: Between 1999 and 2010, 82 consecutive patients with PNSC were treated by surgery and radiotherapy or by definitive (chemo)radiation. Three-dimensional conformal (3DCRT) or highly-conformal intensity-modulated RT (IMRT) was used.

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To assess outcomes, toxicity and quality-of-life (QoL) of patients with parotid gland adenoid cystic carcinoma (PGACC) treated by surgery and postoperative radiotherapy. Between 1995 and 2010, 46 patients with PGACC were treated with parotidectomy±neck dissection followed by radiotherapy. Endpoints were loco-regional control (LRC), distant metastasis-free (DMFS), disease-free (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and QoL.

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Laryngotracheal reconstruction requires a supportive structure with a mucosal lining, which needs a vascular supply in order to regenerate properly. We investigated the necessity of a vascular carrier and mucosal graft when using porous titanium for laryngotracheal reconstruction. Surgical defects of the laryngotracheal complex in 22 rabbits were reconstructed with: (a) porous titanium implanted on a vascularized fascia combined with a buccal mucosal graft (first stage) before transposing to the neck area (second stage); (b) porous titanium implanted on a vascularized fascia (first stage) combined with a mucosal graft (second stage); (c) porous titanium on a pedicled fascia flap; and (d) porous titanium alone.

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Objective: To investigate whether porous titanium can provide a better support for revascularization of a mucosal graft ideal for tracheal reconstruction. In patients with laryngotracheal stenosis or tumor, the mucosa with supporting structures can be damaged, resulting in a defect that has to be reconstructed. Autologous tissues like cartilage and mucosa have been used for reconstruction.

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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.

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