What prognostic factors have impacted the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic oral cancer?

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely adapted for recurrent or metastatic head and neck cancer (RM-HNC), and various studies on its prognostic factors have been reported. We aimed to elucidate the prognostic factors of ICI treatment for RM oral cancer (RM-OC) in a retrospective study. METHODS: We retrospectively reviewed patients with RM-OC treated with ICIs (nivolumab and pembrolizumab) at our department from May 2017 to February 2023. The objective response rate (ORR) for ICI treatment and the relationship between several potential prognostic factors, progression-free survival (PFS), and overall survival (OS) were analyzed statistically. RESULTS: The investigation enrolled 31 patients, 16 with nivolumab and 15 with pembrolizumab. There were no significant differences in the ORR or disease control rate between the nivolumab and pembrolizumab groups (p = 0.4578 and 0.2524). In multivariate analysis, the prognostic nutritional index (PNI) and C-reactive protein to albumin ratio (CAR) exhibited statistical correlations with PFS, whereas the use of antibiotics and proton pump inhibitors (PPIs), neutrophil to lymphocyte ratio (NLR), and PNI demonstrated statistical associations with OS. CONCLUSION: Our findings imply that the use of antibiotics and PPIs, which can modify the gut microbiota, may also serve as a prognostic determinant for ICI treatment in RM-OC, consistent with previous studies. Additionally, PNI may be essential in affecting the survival rates of both PFS and OS and could be an exceedingly valuable inflammatory biomarker for RM-OC.

Three-dimensional ultrastructure and histomorphology of mouse circumvallate papillary taste buds before and after birth using focused ion beam-scanning electron microscope tomography.

Early taste buds are formed from placode cells. Placode cells differentiate into Type I-Ⅲ cells at birth; however, the ultrastructure of these first taste cells remain elusive. Here, we used focused ion beam-scanning electron microscopy (FIB-SEM) to analyze taste buds on the dorsal surface of the circumvallate papilla on embryonic day (E) 18.5 and postnatal day (P) 1.5. The taste buds on E18.5 existed as a mass of immature cells. One of the immature cells extended the cell process to the surface of the epithelium from the taste bud mass. Cytoplasm of this cell contained many mitochondria and vesicles in the apical region. The taste buds at P1.5 had small taste pores and had an onion-shaped structure. Most of the cells in the taste buds extended toward the taste pores. Some of the cells in the taste buds were Type II-like cells with glycogen in their cytoplasm. In this study, it was shown in three dimensions that immature cells extend to the surface of epithelium before the formation of the taste pore. Subsequently, the formation of taste pores and maturation of taste buds progress simultaneously.

Three-Dimensional Analysis of Interstitial Cells in the Smooth Muscle Layer of Murine Vas Deferens Using Confocal Laser Scanning Microscopy and FIB/SEM.

The smooth muscle contraction of the vas deferens has the important function of transporting sperm. Interstitial cells (ICs) play a critical role in the pacing and modulation of various smooth muscle organs by interactions with nerves and smooth muscle. Elucidating the three-dimensional (3D) architecture of ICs is important for understanding their spatial relationship on the mesoscale between ICs, smooth muscle cells (SMCs), and nerves. In this study, the 3D ultrastructure of ICs in the smooth muscle layer of murine vas deferens and the spatial relationships between ICs, nerves, and smooth muscles were observed using confocal laser scanning microscopy and focused ion beam/scanning electron microscopy. ICs have sheet-like structures as demonstrated by 3D observation using modern analytical techniques. Sheet-like ICs have two types of 3D structures, one flattened and the other curled. Multiple extracellular vesicle (EV)-like structures were frequently observed in ICs. Various spatial relations were observed in areas between ICs, nerves, and SMCs, which formed a complex 3D network with each other. These results suggest that ICs in the smooth muscle layer of murine vas deferens may have two subtypes with different sheet-like structures and may be involved in neuromuscular signal transmission via physical interaction and EVs.

Morphological analysis of interstitial cells in murine epididymis using light microscopy and transmission electron microscopy.

Smooth muscle contraction of the epididymis plays an important role in sperm transport. Although PDGFRα-positive interstitial cells (PDGFRα (+) ICs) are thought to be involved in controlling smooth muscle movement via intercellular signaling, they have not yet been reported to date in the epididymis. Therefore, we aimed to investigate the morphological characteristics of PDGFRα (+) ICs in the interstitial space of the murine epididymis. Immunohistochemistry showed that PDGFRα (+) ICs co-labeled with CD34 (PDGFRα (+) CD34 (+) ICs were distributed in the interstitial space of the murine epididymis from the initial segment (IS) to the cauda of the epididymis. PDGFRα (+) ICs that were not co-labeled with CD34 (PDGFRα (+) CD34 (-) ICs) were observed just beneath the epithelium from the corpus to the cauda but not in the IS. Both types of PDGFRα (+) ICs were in close proximity to each other as well as the surrounding nerves and macrophages. In addition, PDGFRα (+) CD34 (-) ICs beneath the epithelium were also in close proximity to the basal cells. Using transmission electron microscopy, we identified ICs that possessed elongated and woven cellular processes and were in close proximity to each other, surrounding the cells in the interstitial space. In the murine epididymis, it is suggested that there are two subtypes of ICs that show different distribution patterns depending on the segment, which may reflect segmental differences in mechanisms of sperm transport, forming a cellular network by physical interactions in the murine epididymis.

Identification of PDGFRα-positive interstitial cells in the distal segment of the murine vas deferens.

Platelet-derived growth factor receptor-α (PDGFRα)-positive interstitial cells (ICs) are widely distributed in various organs and may be involved in the motility of various tubular organs. We, for the first time, aimed to investigate the distribution, immunohistochemical characteristics, and ultrastructure of PDGFRα-positive ICs in murine vas deferens, using confocal laser scanning microscopy, transmission electron microscopy (TEM), and immuno-electron microscopy (immuno-EM). For immunofluorescence, we used antibodies against PDGFRα and other markers of ICs. PDGFRα-positive ICs were distributed widely in the lamina propria, smooth muscles, and serosal layers. Although most PDGFRα-positive ICs labeled CD34, they did not label CD34 in the subepithelial layers. Additionally, PDGFRα-positive ICs were in close proximity to each other, as also to the surrounding cells. TEM and immuno-EM findings revealed that PDGFRα-positive ICs established close physical interactions with adjacent ICs. Extracellular vesicles were also detected around the PDGFRα-positive ICs. Our morphological findings suggest that PDGFRα-positive ICs may have several subpopulations, which can play an important role in intercellular signaling via direct contact with the IC network and the extracellular vesicles in the murine vas deferens. Further investigation on PDGFRα-positive ICs in the vas deferens may lead to understanding the vas deferens mortility.

The retromolar canals and foramina: radiographic observation and application to oral surgery.

PURPOSE: The retromolar canal (RMC) and foramen (RMF) are anatomic variants in the retromolar area of the mandible. The purpose of this study was to clarify the relationship between the RMC and RMF and related complications, and to reveal how the RMC could impact the mandibular anatomy using cone-beam computed tomography (CBCT) and panoramic images (PAN). MATERIALS AND METHODS: CBCT and PAN images of 50 patients were retrospectively analyzed to investigate the morphology of the RMC and RMF, and their impact on impacted third molar surgery and orthognathic surgery. RESULTS: In PAN images, neither the RMC nor RMF was detected. In CBCT images, the RMCs were detected in 26% (13/50) of the patients. A double RMC was detected on one side of one patient. The diameter of the RMC ranged from 0.8 to 2.9 mm (mean; 1.5 ± 0.6 mm), and the RMF ranged from 0.6 to 2.3 mm (mean; 1.1 ± 0.5 mm). No patients experienced unexpected bleeding. Unilateral postoperative hypoesthesia of the buccal gingiva in the molar region was reported in 6.7% of patients with the RMC. CONCLUSIONS: Hypoesthesia of the buccal gingiva in the lower molar region may be the main complication when the RMC is damaged.