Patients with lymphovascular invasion and extracapsular invasion are at a high risk of distant recurrence after preoperative chemoradiotherapy and oesophagectomy. Effective systemic therapy and intensive surveillance are necessary in this group of patients.
Purpose
To characterize histologic changes in the optic nerve and the retina of an end-stage retinitis pigmentosa (RP) patient after long-term implantation with the Argus II retinal prosthesis system.
Methods
Serial cross sections from the patient's both eyes were collected postmortem 6 years after implantation. Optic nerve from both eyes were morphometrically analyzed and compared. Retina underneath and outside the array was analyzed and compared with corresponding regions in the fellow eye.
Results
Although the optic nerve of the implant eye demonstrated significantly more overall atrophy than the fellow eye (
P
< 0.01), the temporal quadrant that retinotopically corresponded to the location of the array did not show additional damage. The total neuron count of the macular area was not significantly different between the two eyes, but the tack locations and their adjacent areas showed significantly fewer neurons than other perimacular areas. There was an increased expression of glial fibrillary acidic protein (GFAP) throughout the retina in the implant eye versus the fellow eye, but there was no significant difference in the cellular retinaldehyde-binding protein (CRALBP) expression. Except for the revision tack site, no significant increase of inflammatory reaction was detected in the implant eye.
Conclusion
Long-term implantation and electrical stimulation with an Argus II retinal prosthesis system did not result in significant tissue damage that could be detected by a morphometric analysis.
Translational Relevance
This study supports the long-term safety of the Argus II device and encourages further development of bioelectronics devices at the retina-machine interface.
Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 μm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 μm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1–49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.
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