Accumulation of secretory vesicles in the lacrimal gland epithelia is related to non-Sjögren's type dry eye in visual display terminal users.

Previous observations in a rat model of a non-Sjögren's syndrome (non-SS) type of dry eye seen in users of visual display terminals (VDT) indicated that secretory vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the condition. Here, to examine this possibility in humans, we compared the lacrimal gland histology and percent SV area in the cytoplasm of acinar epithelial cells using light microscopy and transmission electron microscopy, in patients with VDT work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically examined in lacrimal gland tissue sections. The lacrimal gland acini were larger in the VDT group than in the SS group, and the percent SV area was significantly higher in the VDT group than in the normal controls (P = 0.021) or SS group (P = 0.004). Immunostaining revealed abnormal distributions of VAMP8 in the VDT and SS groups. Rab3D was more strongly expressed in the cytoplasm of acinar epithelial cells in the VDT group than in that of normal controls. The duration of VDT use was significantly longer in the VDT group than in the other groups. These findings suggest that excessive SV accumulation in the acinar epithelia may contribute to the reduced tear secretion in VDT users

Dosimetric and radiobiological analyses of a de-escalation strategy for elective nodal regions in human papillomavirus-associated oropharyngeal cancer

Introduction: In this simulation study, we examined the effects of a de-escalation strategy with a reduced dose to subclinical nodal regions in patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC). Methods: We created two patterns of intensity-modulated radiotherapy for 16 patients with HPV-associated OPC. In the standard and de-escalation plans, the initial field including elective nodal regions received 46 and 30 Gy, followed by 20 and 36 Gy to the cutdown field, respectively. Comparison metrics were set for each organ at risk (OAR). We compared these metric values and the probability of adverse effects based on the normal tissue complication probability (NTCP) model between the two plans. Results: Both plans generally met the dose constraints for the targets and all OAR. Among the comparison metrics, the mean doses to the brain, pharyngeal constrictor muscle, thyroid, and skin and the dose to a 1 % volume of the skin were higher in the standard plan than in the de-escalation plan (P = 0.031, 0.007, < 0.001, < 0.001, and 0.006, respectively). NTCP analyses revealed that the probability of adverse effects in the ipsilateral parotid gland and thyroid was higher in the standard plan than in the de-escalation plan (standard vs. de-escalation plans: ipsilateral parotid gland, 6.4 % vs. 5.0 %, P = 0.016; thyroid, 3.3 % vs. 0.5 %, P < 0.001). Conclusions: A de-escalation strategy with elective nodal regions is a promising treatment to prevent a decline in the quality of life in patients with HPV-associated OPC, particularly xerostomia, dysphagia, and hypothyroidism

Hypothetical mechanism of dry eye in the VDT and SS groups.

<p>VDT, VDT work-related to non-Sjögren's syndrome dry eye; SS, Sjögren's syndrome dry eye.</p

Immunohistochemistry of VAMP8 and Rab3D.

<p>(A), (B): VAMP8 expression in normal controls was localized to the apical membrane of the lacrimal gland epithelia (A, B; 87 years old, Female). (C), (D): In the VDT group, strong VAMP8 immunostaining was present in the cytoplasm and basal side of the lacrimal gland epithelial cells but not at the apical membrane (C, D; VDT-case 3). (E), (F): VAMP8 staining in the SS group was seen close to the basal side of the acinar epithelia (E, F; SS-case 8). A, C, E; Original magnification: ×400, B, D, F; Magnified view of the acinus with asterisk in A, C, E. Scale bars = 20 µm. (G), (H): Rab3D expression in normal controls. Rab3D was expressed at the apical side of the cytoplasm in the lacrimal gland epithelia, but not at the apical membrane, where VAMP8 was expressed (G, H; 87 years old, Female). (I), (J): In the VDT group, strong Rab3D immunostaining was observed in the cytoplasm of the lacrimal gland epithelial cells (I, J; VDT-case 3). (K), (L): In the SS group, faint Rab3D expression was observed at the basal side of the acinar epithelia (K, L; SS-case 8). G, I, K; Original magnification: ×400. H, J, L: Magnified view of the acinus with asterisk in G, I, and K. Scale bars = 20 µm.</p