Explore the vast range of titles available.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a⁺CD103⁺ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) is used to stage regional lymph nodes pathologically and inform prognosis, treatment, and surveillance. To reduce unnecessary surgeries, predictive tools aim to identify those at lowest risk for node-positive disease. The Melanoma Institute of Australia (MIA)'s Prediction Tool for Sentinel Node Metastasis Risk estimates risk of a positive SLNB using patient age and primary melanoma Breslow depth, histologic subtype, ulceration, mitotic rate, and lymphovascular invasion. A single-institution validation was performed of the MIA Calculator with 982 cutaneous melanoma patients that included all relevant clinicopathologic factors and SLNB pathology outcomes. The study evaluated discrimination via receiver operating characteristic (ROC) curves, calibration via calibration plots, and clinical utility via decision curve analysis of the MIA model in various subgroups. The data were fit to MIA model parameters via a generalized linear model to assess the odds ratio of parameters in our dataset. The Calculator demonstrated limited discrimination based on ROC curves (C-statistic, 0.709) and consistently underestimated risk of SLN positivity. It did not provide a net benefit over SLNB performed on all patients or reduce unnecessary procedures in the risk domain of 0% to 16%. Compared with the original development and validation cohorts, the current study cohort had thinner tumors and a larger proportion of acral melanomas. The Calculator generally underestimated SLN positivity risk, including assessment in patients who would be counseled to forego SLNB based on a predicted risk lower than 5%. Recognition of the tool's current limitations emphasizes the need to refine it further for use in medical decision-making.

Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

Background Current American Thyroid Association (ATA) guidelines state that patients with intermediate-risk papillary thyroid cancer (PTC) may benefit from remnant ablation. One criterion for intermediate-risk classification is >5 positive lymph nodes (LNs). We investigate whether performing step-sectioning of LNs increases the metastatic detection rate, thereby influencing ATA risk of recurrence (ROR) classification. Methods A retrospective review was conducted of cases in which ≥ 5 LNs were removed during thyroidectomy and ≤5 LNs were found positive for PTC. Step-sectioning was performed on the original tissue blocks. All slides were re-reviewed by a senior pathologist. Results Twenty patients met study criteria. Step-sectioning significantly increased LN yield compared to standard sectioning. In total, we found 12 new positive lymph nodes; seven (58%) were in totally new lymph nodes, while five (42%) were in lymph nodes previously read as negative. All newly discovered metastases were classified as micrometastases (≤2 mm). Of the 15 patients originally classified as low-risk, the step-sectioning protocol impacted two patients (13%), increasing ROR stratification. Conclusion Intensive step-sectioning reveals additional micrometastases. More detailed analysis did not identify clinically significant nodal disease likely to impact the clinical course of patients in this study. Our study supports current standards of pathology specimen handling related to LN assessment and the impact on ATA ROR classification. Nonetheless, it is important for clinicians to understand their institution’s sectioning protocol utilized to report positive and total LN counts, which could impact ATA risk stratification and denote the comprehensive nature of the LN dissection that was performed.

Recognized as a distinct phase of cancer care by a 2005 Institute of Medicine report, the goals of survivorship include: the prevention and detection of new cancers, surveillance for recurrence, recognition, and management of treatmentrelated side effects, psychological care, and coordination of care among healthcare providers (5,6). Coordination Along with storing and organizing thyroid cancer patients' medical records, the TCC streamlines communication among physicians, aids in surveillance for recurrence, and educates patients in recognizing and managing treatment side effects. In our practice, we have seen a high rate of participation and satisfaction. Since 2013 when the database was established, over 3,000 patients and over 400 physicians have registered for the TCC. Critical data points allowing for appropriate postoperative staging (American Joint Committee on Cancer, MACIS [i.e., metastases, age, completeness of resection, invasion, and size] score, and American Thyroid Association risk of recurrence) and follow-up biochemical and imaging information are considered a priority.

Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.

Background For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) is used to stage regional lymph nodes pathologically and inform prognosis, treatment, and surveillance. To reduce unnecessary surgeries, predictive tools aim to identify those at lowest risk for node-positive disease. The Melanoma Institute of Australia (MIA)’s Prediction Tool for Sentinel Node Metastasis Risk estimates risk of a positive SLNB using patient age and primary melanoma Breslow depth, histologic subtype, ulceration, mitotic rate, and lymphovascular invasion. Methods A single-institution validation was performed of the MIA Calculator with 982 cutaneous melanoma patients that included all relevant clinicopathologic factors and SLNB pathology outcomes. The study evaluated discrimination via receiver operating characteristic (ROC) curves, calibration via calibration plots, and clinical utility via decision curve analysis of the MIA model in various subgroups. The data were fit to MIA model parameters via a generalized linear model to assess the odds ratio of parameters in our dataset. Results The Calculator demonstrated limited discrimination based on ROC curves (C-statistic, 0.709) and consistently underestimated risk of SLN positivity. It did not provide a net benefit over SLNB performed on all patients or reduce unnecessary procedures in the risk domain of 0% to 16%. Compared with the original development and validation cohorts, the current study cohort had thinner tumors and a larger proportion of acral melanomas. Conclusions The Calculator generally underestimated SLN positivity risk, including assessment in patients who would be counseled to forego SLNB based on a predicted risk lower than 5%. Recognition of the tool’s current limitations emphasizes the need to refine it further for use in medical decision-making.

We investigate how vibrotactile wrist feedback can enhance spatial guidance for handheld tool movement in optical see-through augmented reality (AR). While AR overlays are widely used to support surgical tasks, visual occlusion, lighting conditions, and interface ambiguity can compromise precision and confidence. To address these challenges, we designed a multimodal system combining AR visuals with a custom wrist-worn haptic device delivering directional and state-based cues. A formative study with experienced surgeons and residents identified key tool maneuvers and preferences for reference mappings, guiding our cue design. In a cue identification experiment (N=21), participants accurately recognized five vibration patterns under visual load, with higher recognition for full-actuator states than spatial direction cues. In a guidance task (N=27), participants using both AR and haptics achieved significantly higher spatial precision (5.8 mm) and usability (SUS = 88.1) than those using either modality alone, despite having modest increases in task time. Participants reported that haptic cues provided reassuring confirmation and reduced cognitive effort during alignment. Our results highlight the promise of integrating wrist-based haptics into AR systems for high-precision, visually complex tasks such as surgical guidance. We discuss design implications for multimodal interfaces supporting confident, efficient tool manipulation.

Purpose: In this paper, we develop and clinically evaluate a depth-only, markerless augmented reality (AR) registration pipeline on a head-mounted display, and assess accuracy across small or low-curvature anatomies in real-life operative settings. Methods: On HoloLens 2, we align Articulated HAnd Tracking (AHAT) depth to Computed Tomography (CT)-derived skin meshes via (i) depth-bias correction, (ii) brief human-in-the-loop initialization, (iii) global and local registration. We validated the surface-tracing error metric by comparing \"skin-to-bone\" relative distances to CT ground truth on leg and foot models, using an AR-tracked tool. We then performed seven intraoperative target trials (feet x2, ear x3, leg x2) during the initial stage of fibula free-flap harvest and mandibular reconstruction surgery, and collected 500+ data per trial. Results: Preclinical validation showed tight agreement between AR-traced and CT distances (leg: median |Delta d| 0.78 mm, RMSE 0.97 mm; feet: 0.80 mm, 1.20 mm). Clinically, per-point error had a median of 3.9 mm. Median errors by anatomy were 3.2 mm (feet), 4.3 mm (ear), and 5.3 mm (lower leg), with 5 mm coverage 92-95%, 84-90%, and 72-86%, respectively. Feet vs. lower leg differed significantly (Delta median ~1.1 mm; p < 0.001). Conclusion: A depth-only, markerless AR pipeline on HMDs achieved ~3-4 mm median error across feet, ear, and lower leg in live surgical settings without fiducials, approaching typical clinical error thresholds for moderate-risk tasks. Human-guided initialization plus global-to-local registration enabled accurate alignment on small or low-curvature targets, improving the clinical readiness of markerless AR guidance.