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Search Results (1,227)

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Keywords = oral squamous cell carcinoma

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12 pages, 209 KiB  
Review
Prognosis, Controversies and Assessment of Bone Erosion or Invasion of Oral Squamous Cell Carcinoma
by Ahmed Ata Alfurhud
Diagnostics 2025, 15(1), 104; https://doi.org/10.3390/diagnostics15010104 (registering DOI) - 4 Jan 2025
Viewed by 183
Abstract
Objectives: To discuss the prognostic outcomes, controversies and assessment of bone erosion or invasion of oral squamous cell carcinoma (OSCC). Methods: A structured literature review was conducted to critically analyse relevant evidence. The Web of Science database was searched using specific keywords [...] Read more.
Objectives: To discuss the prognostic outcomes, controversies and assessment of bone erosion or invasion of oral squamous cell carcinoma (OSCC). Methods: A structured literature review was conducted to critically analyse relevant evidence. The Web of Science database was searched using specific keywords aligned with the review question. After identifying initial studies, their references were also reviewed to include any additional relevant publications, ensuring a comprehensive evaluation of the available evidence. Results: The search identified 11 relevant studies, including 5 from the initial search and 6 from reference review. The significance of bone involvement is unclear in OSCC, with varying definitions of cortical bone erosion and medullary bone infiltration contributing to conflicting results regarding the prognostic significance of bone involvement. The majority of evidence stems from retrospective cohort studies without clear study criteria and a lack of power to draw valid conclusions. Conclusions: There are currently a lack of high-quality studies assessing bone invasion in OSCC. While there appears to be some evidence that medullary bone infiltration is prognostic, further well-designed studies are warranted. Full article
(This article belongs to the Special Issue Advances in Oral Diseases Diagnosis and Management: 2nd Edition)
19 pages, 8622 KiB  
Article
Richness for Tumor-Infiltrating B-Cells in the Oral Cancer Tumor Microenvironment Is a Prognostic Factor in Early-Stage Disease and Improves Outcome in Advanced-Stage Disease
by Irene H. Nauta, Dennis N. L. M. Nijenhuis, Sonja H. Ganzevles, Pamela I. Raaff, Jan Kloosterman, Elisabeth Bloemena, Ruud H. Brakenhoff, C. René Leemans and Rieneke van de Ven
Cancers 2025, 17(1), 113; https://doi.org/10.3390/cancers17010113 - 1 Jan 2025
Viewed by 444
Abstract
Background/Objectives: Most studies on the interaction between the immune system and cancer focus on T-cells, whereas studies on tumor-infiltrating B-lymphocytes (TIL-Bs) are still underrepresented. The aim of this study was to assess the prognostic impact of TIL-Bs in early- and advanced-stage oral cavity [...] Read more.
Background/Objectives: Most studies on the interaction between the immune system and cancer focus on T-cells, whereas studies on tumor-infiltrating B-lymphocytes (TIL-Bs) are still underrepresented. The aim of this study was to assess the prognostic impact of TIL-Bs in early- and advanced-stage oral cavity squamous cell carcinoma (OCSCC). Methods: In total, 222 OCSCCs were studied. Consecutive sections were stained for CD45 and CD19. OCSCCs were categorized as either “TIL-B-rich” or “TIL-B-poor”, and the survival of both groups was analyzed. Similar analyses were performed for CD45+ TILs and the CD19/CD45 ratio. Matched subgroups of twelve TIL-B-rich and TIL-B-poor tumors were stained for CD3 and CD8 to determine differences in T-cell infiltration, and further spatial interaction between T- and B-cells was evaluated in six samples. Results: Five-year OS was 75.0% for TIL-B-rich and 54.2% for TIL-B-poor OCSCCs (p < 0.001). The survival benefit of TIL-B-rich OCSCCs remained significant after correction for the histopathological characteristics (p = 0.033). While for early-stage tumors, TIL-B richness benefited OS independent of demographic-, clinical, or histopathological features, for advanced-stage disease, this was not the case, although a clear benefit of a TIL-B-rich status was observed, specifically up until 36 months after diagnosis. TIL-B-rich tumors contained more CD3+ TILs (p = 0.007), but not CD8+ TILs. Spatial characterization suggested that TIL-Bs mostly co-localized with CD3+CD8− TILs and that this interaction was increased in TIL-B-rich OCSCC. Conclusions: The presence of TIL-Bs is associated with a more favorable prognosis in OCSCC, in particular for early-stage disease. Full article
(This article belongs to the Special Issue Feature Papers in Section "Tumor Microenvironment")
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<p>Immunohistochemical analysis of CD45 and CD19 in OCSCC. On the top right of each image, an overview of the slide is shown. The red box identifies the area that has been magnified in the main image. (<b>A</b>) Two examples of TIL-rich (CD45 &gt; median) and TIL-B-rich (CD19 &gt; median) OCSCCs. (<b>B</b>) Two examples of TIL-rich (CD45 &gt; median) but TIL-B-poor (CD19 ≤ median) OCSCCs. The white circle in the tumor area is caused by a punch biopsy that was taken from the FFPE block for another study. This white area was excluded from the calculated tumor area.</p>
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<p>Immunohistochemical analysis of CD45 and CD19 in OCSCC. On the top right of each image, an overview of the slide is shown. The red box identifies the area that has been magnified in the main image. (<b>A</b>) Two examples of TIL-rich (CD45 &gt; median) and TIL-B-rich (CD19 &gt; median) OCSCCs. (<b>B</b>) Two examples of TIL-rich (CD45 &gt; median) but TIL-B-poor (CD19 ≤ median) OCSCCs. The white circle in the tumor area is caused by a punch biopsy that was taken from the FFPE block for another study. This white area was excluded from the calculated tumor area.</p>
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<p>Survival curves of TIL-B-rich (red line) and TIL-B-poor (blue line) OCSCCs. (<b>A</b>) Five-year OS was 75.0% for TIL-B-rich OCSCCs and 54.2% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> &lt; 0.001). (<b>B</b>) Separate survival curves of pathological disease stage I–II (“early-stage disease”) OCSCC. Five-year OS of pathological disease stage I–II was 91.2% for TIL-B-rich OCSCCs and 55.3% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> &lt; 0.001). (<b>C</b>) Separate survival curves of pathological disease stage III–IV (“advanced-stage disease”) OCSCC. Five-year OS of pathological disease stage III–IV was 57.7% for TIL-B-rich OCSCCs and 52.6% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> = 0.212).</p>
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<p>Survival curves of TIL-B-rich (red line) and TIL-B-poor (blue line) OCSCCs. (<b>A</b>) Five-year OS was 75.0% for TIL-B-rich OCSCCs and 54.2% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> &lt; 0.001). (<b>B</b>) Separate survival curves of pathological disease stage I–II (“early-stage disease”) OCSCC. Five-year OS of pathological disease stage I–II was 91.2% for TIL-B-rich OCSCCs and 55.3% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> &lt; 0.001). (<b>C</b>) Separate survival curves of pathological disease stage III–IV (“advanced-stage disease”) OCSCC. Five-year OS of pathological disease stage III–IV was 57.7% for TIL-B-rich OCSCCs and 52.6% for TIL-B-poor OCSCCs (<span class="html-italic">p</span> = 0.212).</p>
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<p>Survival curves of OCSCCs with a high CD19/CD45 ratio (red line) and OCSCCs with a low CD19/CD45 ratio (blue line). Five-year OS was 72.0% for OCSCCs with a high CD19/CD45 ratio and 57.1% for OCSCCs with a low CD19/CD45 ratio (<span class="html-italic">p</span> = 0.008).</p>
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<p>Quantification of CD8+ and CD3+ T-lymphocytes in TIL-B-rich vs. TIL-B-poor OCSCC. (<b>A</b>) CD8+ T-lymphocytes and (<b>B</b>) CD3+ T-lymphocytes were quantified in 12 TIL-B-poor and 12 TIL-B-rich OCSCCs from the original cohort (<span class="html-italic">N</span> = 222), which were matched on pT-stage and growth pattern of invasion. Both cohesive and non-cohesive growing tumors were included. Mann–Whitney tests were performed to determine the statistical significance in T-cell counts between TIL-B-poor and TIL-B-rich OCSCC using Graphpad Prism 8.</p>
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<p>Spatial immune infiltrate analysis of TIL-B-poor and TIL-B-rich OCSCC using mfIHC. Six TIL-B-poor and six TIL-B-rich samples were matched based on the pattern of invasion (cohesive or non-cohesive) and tumor stage (early-stage or advanced-stage). In each group, three early-stage and three advanced-stage OCSCCs were stained and analyzed. One early-stage TIL-B-poor sample was excluded from the analysis due to unreliable staining quality. (<b>A</b>) Representation of the mfIHC panel optimized to detect CD44v6<sup>+</sup> tumor cells, CD163<sup>+</sup> macrophages, CD19<sup>+</sup> B-cells, CD3<sup>+</sup>, CD3<sup>+</sup>CD8<sup>+</sup>, CD3<sup>+</sup>CD8<sup>−</sup> FoxP3<sup>−</sup> (CD4<sup>+</sup> helper) T-lymphocytes, and CD3<sup>+</sup>CD8<sup>−</sup>FoxP3<sup>+</sup>Treg cells. (<b>B</b>) Cell proportions relative to the total number of detected cells within the tumor area. Open bars represent TIL-B-poor tumors, and closed bars represent TIL-B-rich tumors. The asterisk represents a statistical significant difference between the two appointed categories. (<b>C</b>) Spatial analysis was performed by a minimal distance analysis. The shortest distance from each TIL-B to each of the other immune subsets was calculated and corrected for the number of TIL-Bs. (<b>D</b>) Mean of the minimal distance between TIL-Bs and the other immune subsets. Open bars represent TIL-B-poor OCSCC, and closed bars represent TIL-B-rich OCSCC. The asterisk represents a statistical significant difference between the two appointed categories. Unpaired <span class="html-italic">t</span>-tests were performed between TIL-B-rich and TIL-B-poor conditions using Graphpad Prism 8.</p>
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<p>Overview of TIL-B-poor and TIL-B-rich early-stage (<b>A</b>) and advanced-stage (<b>B</b>) OCSCC mfIHC samples.</p>
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<p>Overview of TIL-B-poor and TIL-B-rich early-stage (<b>A</b>) and advanced-stage (<b>B</b>) OCSCC mfIHC samples.</p>
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18 pages, 2023 KiB  
Systematic Review
Vulvar Epidermolytic Hyperkeratosis: A Comprehensive Systematic Review of Case Reports and Series
by Miruna Ioana Cristescu, Elena Codruța Cozma, Cristina Beiu, Irina Tudose, Selda Ali, Anca Bobircă and Liliana Gabriela Popa
J. Clin. Med. 2025, 14(1), 94; https://doi.org/10.3390/jcm14010094 - 27 Dec 2024
Viewed by 331
Abstract
Background: Vulvar epidermolytic hyperkeratosis (EHK) is an exceedingly rare dermatological condition, often presenting as solitary or multiple lesions in the vulvar region. Due to its clinical resemblance to other vulvar disorders, such as condyloma acuminatum, Bowenoid papulosis, and squamous cell carcinoma, vulvar [...] Read more.
Background: Vulvar epidermolytic hyperkeratosis (EHK) is an exceedingly rare dermatological condition, often presenting as solitary or multiple lesions in the vulvar region. Due to its clinical resemblance to other vulvar disorders, such as condyloma acuminatum, Bowenoid papulosis, and squamous cell carcinoma, vulvar EHK poses significant diagnostic challenges. While individual case reports and small case series have documented instances of vulvar EHK, comprehensive studies systematically consolidating the clinical, histopathological, and therapeutic aspects of this condition remain lacking. Objectives: To address this gap, this systematic review consolidates all available case reports and case series on vulvar EHK. The review aims to provide a comprehensive analysis of clinical presentations, histopathological features, diagnostic challenges, treatment approaches, and patient outcomes. Methods: We conducted a systematic review following the PRISMA guidelines. We searched multiple databases (PubMed, Web of Science, Scopus) for studies published up to 30 September 2024. Only case reports and case series with histopathologically confirmed vulvar EHK were included, as no higher-level studies (e.g., randomized controlled trials or cohort studies) were available due to the rarity of this condition. Exclusion criteria were male cases, oral EHK or other unrelated conditions, and literature reviews. We extracted and analyzed data on: patient demographics, time to diagnosis, anatomical distribution, clinical presentation, associated symptoms, histopathological features, patient history, risk factors, HPV status, treatment, and outcomes. Risk of bias was assessed using the CARE checklist and JBI Checklist for Case Series. Additionally, original clinical and histopathological images from our department were included to enhance the review. Results: A total of 19 studies, encompassing 30 cases of histopathologically confirmed vulvar EHK, were identified. Most cases presented with hyperkeratotic plaques and papules localized on the labia majora. Histopathological analysis consistently revealed hyperkeratosis, acanthosis, and vacuolar degeneration in the granular and spinous layers. Misdiagnosis was common, with lesions frequently mistaken for condyloma acuminatum or other vulvar neoplasms. Conservative management, including observation and topical therapies, was associated with disease stability in asymptomatic cases, while surgical excision demonstrated complete remission in all cases where it was employed. The rarity of vulvar EHK and reliance on case reports and series limit the generalizability of findings. Conclusions: Vulvar EHK is often misdiagnosed due to its similarity to malignancies and sexually transmitted infections. This review, the first of its kind, highlights the importance of prompt histopathological diagnosis to avoid the psychological impact of a cancer or sexually transmitted disease diagnosis and unnecessary, distressing, or aggressive treatments. Further research is needed to explore the role of HPV in vulvar EHK and to establish standardized diagnostic and treatment guidelines. Full article
(This article belongs to the Section Dermatology)
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<p>PRISMA flow diagram: Nineteen relevant publications were identified through database searching and were all included in the qualitative and quantitative synthesis. * records excluded based on title and abstract screening for not meeting inclusion criteria; ** records excluded during full-text review due to irrelevance or lack of histopathological confirmation.</p>
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<p>Representative clinical image of a patient with vulvar EHK, showing multiple grey-colored, hyperkeratotic papules coalescing into plaques located bilaterally on the labia majora (clinical photograph taken at Elias Emergency University Hospital, Bucharest, Romania).</p>
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<p>Hematoxylin–eosin stain showing hyperorthokeratosis, focal hypergranulosis, and the presence of irregular keratohyalin granules, along with vacuolar degeneration of the granular and superficial spinous layers, and a minimal lymphocytic inflammatory infiltrate in the superficial dermis ((<b>A</b>): 50×; (<b>B</b>): 100×; (<b>C</b>): 200×; (<b>D</b>): 400×) (histopathology images from the Pathology Department at Elias Emergency University Hospital, Bucharest, Romania).</p>
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19 pages, 2262 KiB  
Article
Leveraging Autofluorescence for Tumor Detection, Diagnosis, and Accurate Excision with Surgical Margin Assessment in Tumor Excision
by Antonis Perdiou, Ramona Dumitrescu, Daniela Jumanca, Octavia Balean, Ruxandra Sava-Rosianu, Serban Talpos, Dacian Virgil Lalescu and Atena Galuscan
Dent. J. 2025, 13(1), 10; https://doi.org/10.3390/dj13010010 - 26 Dec 2024
Viewed by 267
Abstract
Background/Objectives: Oral cancer ranks among the top ten cancers globally, with a five-year survival rate below 50%. This study aimed to evaluate the effectiveness of autofluorescence-guided surgery compared to standard surgical methods in identifying tumor-free margins and ensuring complete excision. Methods: A prospective [...] Read more.
Background/Objectives: Oral cancer ranks among the top ten cancers globally, with a five-year survival rate below 50%. This study aimed to evaluate the effectiveness of autofluorescence-guided surgery compared to standard surgical methods in identifying tumor-free margins and ensuring complete excision. Methods: A prospective cohort of 80 patients was randomized into two groups: the control group underwent excision with a 10 mm margin based on clinical judgment, while the experimental group used autofluorescence guidance with a 5 mm margin beyond fluorescence visualization loss. Autofluorescence imaging was performed using the OralID device, which employs a 405 nm excitation laser to detect abnormal tissue. Ethical approval was obtained from the “Spitalul Clinic Municipal de Urgență Timișoara” Ethics Committee (approval number 08/26.02.2021), and the trial was registered at the University of Medicine and Pharmacy Timisoara (trial no. 59/25.11.2021). A double analysis was conducted: a primary analysis of the full cohort and a subgroup analysis focusing on squamous cell carcinoma (control: n = 19; experimental: n = 24). Histopathological analysis was the gold standard for margin evaluation, with margins coded as tumor-free margins (0), close (1), or infiltrated (2). Results: Statistically significant differences were observed in tumor-free margins between the control (73.17%) and experimental (97%) groups (p = 0.003). Subgroup analysis for SCC showed no significant difference (control: 84.21%; experimental: 95.83%; p = 0.306). Tumor location also differed significantly (p = 0.011), while other baseline variables, such as tumor type and patient characteristics, showed no significant differences. Conclusions: Autofluorescence-guided surgery improves the detection of tumor-free margins and may serve as an effective adjunct in oral cancer management. Larger studies are recommended to confirm these findings. Full article
(This article belongs to the Special Issue Advanced Research on Oral Cancer and Dental Implants)
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<p>OralID device and protective glasses for autofluorescence imaging: (<b>a</b>) OralID device and protective glasses [<a href="#B20-dentistry-13-00010" class="html-bibr">20</a>]. (<b>b</b>) Complete setup, including protective glasses, OralID flashlight, and smartphone attachment for imaging.</p>
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<p>Tongue tumor. (<b>a</b>) Image taken in normal light. (<b>b</b>) Image taken with autofluorescence device.</p>
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<p>Correlation and <span class="html-italic">p</span>-value of all variables.</p>
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<p>Correlation and <span class="html-italic">p</span>-value of all variables.</p>
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10 pages, 3495 KiB  
Review
Prospects for Narrow Band Imaging Magnification Endoscopy in Oral Lesions: Recommendations from Oral and Maxillofacial Surgeons and a Gastroenterologist
by Toshimi Chiba, Airi Ota, Taifu Hirano, Tadashi Kawai, Atsushi Ogawa and Hiroyuki Yamada
Cancers 2025, 17(1), 21; https://doi.org/10.3390/cancers17010021 - 25 Dec 2024
Viewed by 211
Abstract
Narrow band imaging (NBI) magnification endoscopy for the diagnosis of early-stage oral cavity-related cancer and precancerous lesions can recognize oral lesions as brownish areas, and can observe intraepithelial papillary capillary loops (IPCLs) in the mucosa and submucosa to make a qualitative diagnosis of [...] Read more.
Narrow band imaging (NBI) magnification endoscopy for the diagnosis of early-stage oral cavity-related cancer and precancerous lesions can recognize oral lesions as brownish areas, and can observe intraepithelial papillary capillary loops (IPCLs) in the mucosa and submucosa to make a qualitative diagnosis of the lesion and highlight the mucosal surface microstructure to facilitate appropriate diagnosis and early treatment. IPCLs are classified from Type 0 to IV: Type 0 is normal mucosa or no blood vessels observed, e.g., in keratinization; Type I is mainly normal mucosa; Type II is mainly inflammatory sites or non-malignant lesions; Type III is mainly precancerous or suspected malignant lesions; and Type IV is cancerous or malignant lesions. NBI magnification endoscopy is a useful noninvasive method for identifying the malignant transformation of oral potentially malignant disorders (OPMDs). Oral lesions classified as IPCL Type II or higher are atypical epithelial or oral squamous cell carcinoma (OSCC); oral biopsy is recommended for early and accurate diagnosis, and is an indicator of the appropriate biopsy site in the follow-up for OPMDs. In the future, the accuracy of NBI magnification endoscopy for malignant transformation of OPMDs and OSCC will be further confirmed. Full article
(This article belongs to the Section Clinical Research of Cancer)
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<p>Type 0 is shown in the circle: No vessels are observed due to normal mucosa or keratinisation, etc.</p>
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<p>Type I is shown in the circle: Regular brown dots are observed when IPCLs are perpendicular to the mucosa, and waved lines are observed when running parallel. Most of the mucosa is normal.</p>
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<p>Type II is shown in the circle: IPCLs are dilated and crossing. They are mainly at inflammatory sites or non-malignant lesions.</p>
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<p>Type III is shown in the circle: IPCLs are further elongated and meandering. This is mainly seen in precancerous or suspected malignant lesions.</p>
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<p>Type IV is shown in the circle: IPCLs are characterized by large vessels, destruction of looped vascular structures, and angiogenesis. This suggests the possibility of cancerous or malignant lesions.</p>
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9 pages, 2443 KiB  
Case Report
A Case of Application of Computer-Aided Design and Manufacturing Technology and Extended Reality Surgical Assistance to Marginal Mandibulectomy
by Takahiro Nakada, Masahide Koyachi, Keisuke Sugahara, Akihiro Nishiyama, Mana Kawakami, Shintaro Nakajima, Kotaro Tachizawa, Kento Odaka, Satoru Matsunaga, Maki Sugimoto and Akira Katakura
J. Clin. Med. 2025, 14(1), 8; https://doi.org/10.3390/jcm14010008 - 24 Dec 2024
Viewed by 267
Abstract
Background/Objectives: Mandibular gingival squamous cell carcinoma (SCC) is the second most common oral cancer after tongue cancer. As these carcinomas often invade the mandible early, accurately defining the resection extent is important. This report highlights the use of preoperative virtual surgery data, computer-aided [...] Read more.
Background/Objectives: Mandibular gingival squamous cell carcinoma (SCC) is the second most common oral cancer after tongue cancer. As these carcinomas often invade the mandible early, accurately defining the resection extent is important. This report highlights the use of preoperative virtual surgery data, computer-aided design and manufacturing (CAD/CAM) technology, surgical guidance, and extended reality (XR) support in achieving highly accurate marginal mandibulectomy without recurrence or metastasis. Methods: CT imaging data obtained a month before surgery were imported into Materialize Mimics and Materialize Magics (Materialize, Leuven, Belgium, Ver22.0) CAD/CAM software and used to design an osteotomy guide. An STL file was generated, and the guide was fabricated using a 3D printer (Objet 260 Connex; Stratasys Ltd., Eden Prairie, MN, USA) prior to the operation. An XR application, installed on a HoloLens (Microsoft, WA, USA) head-mounted display, projected a hologram onto the surgical field. Results: The rapid intraoperative diagnostic tests were negative, and histopathology confirmed SCC without vascular or perineural invasion. No complications, including occlusal or feeding problems and sensory abnormalities, were observed. Postoperative imaging 3 years later showed no recurrence. Conclusions: Combining CAD/CAM and XR techniques for mandibulectomy may improve surgical accuracy and safety in oral and maxillofacial surgeries, whereas in-house 3D printing aids in managing tumor progression. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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<p>Preoperative intraoral photograph. Ulceration with a coarse surface, erythema, and white spots are seen from the interdental papilla between the mandibular right first and second molars to the center of the mandibular right first premolar.</p>
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<p>Preoperative imaging findings. (<b>a</b>) Preoperative panoramic radiograph. No significant bone destruction is observed. (<b>b</b>) Infiltration is observed in the cortical bone in the mandibular right second premolar region. (<b>c</b>) Short tau inversion recovery magnetic resonance imaging (MRI) displaying a high signal intensity area measuring 23 mm anteroposteriorly in the mandibular right first premolar to second molar region.</p>
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<p>CAD/CAM-based osteotomy planning and guide. (<b>a</b>) The red area indicates the set resection area, and the mandibular canal is shown in blue; (<b>b</b>) osteotomy guide fabricated using CAD/CAM technology.</p>
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<p>XR application design and implementation. (<b>a</b>,<b>b</b>) Application design. The area shown in red is the resection range, the area shown in light blue is the mandibular canal, and the areas shown in green and purple denote the resection angles; (<b>c</b>) hologram installed on HoloLens; (<b>d</b>) registration markers created using CAD/CAM. (<b>e</b>) The hologram was automatically superimposed on the surgical field in three dimensions using registration markers 149.</p>
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<p>Preoperative discussion and intraoperative use of XR technology. (<b>a</b>) The holograms are shared among the surgeons and discussed preoperatively in the metaverse; (<b>b</b>) the surgeon operates while wearing the HoloLens.</p>
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<p>(<b>a</b>) Resection is performed using the osteotomy guide. (<b>b</b>) After resection, tie-over is performed, and a protective floor is attached. (<b>c</b>) All excised specimens have negative margins, and the histopathological diagnosis is squamous cell carcinoma, with no vascular or perineural invasion.</p>
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<p>The bone surface error is measured by superimposing the 1-month postoperative CT image and the 3D image of the preoperative virtual surgery. (<b>a</b>) Bone surface error between Tv and T1 within 1 mm. (<b>b</b>) Bone surface error between Tv and T1 within 2 mm.</p>
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<p>Postoperative 3-year follow-up imaging. (<b>a</b>,<b>b</b>) OPG and CT at the 3-year follow-up shows no recurrence and no sensory abnormalities in the inferior alveolar nerve.</p>
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15 pages, 1486 KiB  
Review
Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review
by Kohei Okuyama and Souichi Yanamoto
Cancers 2024, 16(24), 4276; https://doi.org/10.3390/cancers16244276 - 23 Dec 2024
Viewed by 381
Abstract
Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva [...] Read more.
Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva shows a protective effect against oral cancer development, once tumor formation occurs, it may be involved in tumor progression and metastasis via exosomes and microRNAs. This review discusses the essential role of saliva; its relationship with the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC); liquid biopsy tools for early diagnosis and monitoring of HNSCC; and the potential of exosomes as therapeutic agents. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
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<p>General and essential roles of saliva for oral health and systemic influences.</p>
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<p>Salivary roles for oral cancer generation, progression, and metastasis. Red arrows indicate rise, increase, or uptake.</p>
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<p>Engineered/Salivary exosomes as potential therapeutic agents.</p>
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22 pages, 10397 KiB  
Article
Mannich Base Derived from Lawsone Inhibits PKM2 and Induces Neoplastic Cell Death
by Lucas Rubini-Dias, Tácio V. A. Fernandes, Michele P. de Souza, Déborah Hottz, Afonso T. Arruda, Amanda de A. Borges, Gabriel Ouverney, Fernando de C. da Silva, Luana da S. M. Forezi, Gabriel Limaverde-Sousa and Bruno K. Robbs
Biomedicines 2024, 12(12), 2916; https://doi.org/10.3390/biomedicines12122916 - 21 Dec 2024
Viewed by 576
Abstract
Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as a promising target for disrupting the metabolic adaptability of tumor cells. This study explores the potential of the Mannich base derived from lawsone (MB-6a) to [...] Read more.
Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as a promising target for disrupting the metabolic adaptability of tumor cells. This study explores the potential of the Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and in silico. Methods: The antiproliferative potential of MB-6a was tested using MTT assay in various cell lines, including SCC-9, Hep-G2, HT-29, B16-F10, and normal human gingival fibroblast (HGF). The inhibition of PKM2 mediated by MB-6a was assessed using an LDH-coupled assay and by measuring ATP production. Docking studies and molecular dynamics calculations were performed using Autodock 4 and GROMACS, respectively, on the tetrameric PKM2 crystallographic structure. Results: The Mannich base 6a demonstrated selective cytotoxicity against all cancer cell lines tested without affecting cell migration, with the highest selectivity index (SI) of 4.63 in SCC-9, followed by B16-F10 (SI = 3.9), Hep-G2 (SI = 3.4), and HT-29 (SI = 2.03). The compound effectively inhibited PKM2 glycolytic activity, leading to a reduction of ATP production both in the enzymatic reaction and in cells treated with this naphthoquinone derivative. MB-6a showed favorable binding to PKM2 in the ATP-bound monomers through docking studies (PDB ID: 4FXF; binding affinity scores ranging from −6.94 to −9.79 kcal/mol) and MD simulations, revealing binding affinities stabilized by key interactions including hydrogen bonds, halogen bonds, and hydrophobic contacts. Conclusions: The findings suggest that MB-6a exerts its antiproliferative activity by disrupting cell glucose metabolism, consequently reducing ATP production and triggering energetic collapse in cancer cells. This study highlights the potential of MB-6a as a lead compound targeting PKM2 and warrants further investigation into its mechanism of action and potential clinical applications. Full article
(This article belongs to the Special Issue Drug Resistance and Novel Targets for Cancer Therapy—Second Edition)
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<p>Chemical structure of Mannich base derived from lawsone <b>MB-6a</b>.</p>
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<p>Substance <b>MB-6a</b> inhibited cell proliferation but did not impair migration at a sublethal concentration. (<b>A</b>) MTT assay results with <b>MB-6a</b>. Nonlinear regression curves representing cell viability reduction induced by substance <b>MB-6a</b> in SCC-9, HT-29, Hep-G2, B16-F10, and HGF cell lines. The graph represents the curve generated by the number of cells vs. concentration (log 10 µM). (<b>B</b>) Cell migration assay using SCC-9 cells. Images represent the scratch (wound) from 0 to 24 h in non-treated cells (DMSO) and treated with a sublethal concentration (7.03 µM) of <b>MB-6a</b>. (<b>C</b>) Wound width throughout the time. The percentage of wound width after treatment with <b>MB-6a</b> and the control (DMSO) at different time points are represented as mean ± SEM. Results were calculated from at least three independent experiments.</p>
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<p>PKM2 activity upon <b>MB-6a</b> treatment. (<b>A</b>) Glycolytic activity of PKM2 was inhibited by <b>MB-6a</b>. LDH coupled assay indicated dose-dependent inhibition of PKM2 activity. Nonlinear regression curves show PKM2 activity after treatment with <b>MB-6a</b> at different concentrations (squares). The control, Couma. 6e, is represented by circles, while negative control DMSO is represented by triangles. (<b>B</b>) Naphthoquinone <b>MB-6a</b> suppressed ATPase activity of PKM2. The degree of inhibition in ATP production by <b>MB-6a</b> or the control at a concentration equal to 1 × IC<sub>50</sub> is depicted. (<b>C</b>) Production of ATP in SCC-9 is reduced by <b>MB-6a</b>. Intracellular ATP levels were measured after treatment with four different concentrations of <b>MB-6a</b>. DMSO was used as the negative control for all assays. Results represent mean ± SEM from at least three independent experiments.</p>
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<p>Two-dimensional interaction diagram of <b>MB-6a</b> best-scoring pose of <b>MB-6a</b> with PKM2. The diagram represents the chain B<sub>PKM2</sub>-<b>MB-6a</b>-B complex, with key residues labeled and colored based on their type: negatively charged (orange), positively charged (blue), polar (light blue), and hydrophobic (light green). Two hydrogen bonds (indicated by purple arrows) and two salt bridges (red/blue gradient lines) were formed between the lawsone moiety and nearby residues. Additionally, a cation-π interaction (red line) was formed. The chlorobenzene region was solvent-exposed, as indicated by the gray circle.</p>
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<p>Conformational analysis of <b>MB-6a</b> binding to PKM2. (<b>A</b>) RMSD evolution over 300 ns of MD simulation for each <b>MB-6a</b> molecule (<b>MB-6a</b>-A to <b>MB-6a</b>-D), showing structural stability within 2Å deviation. The right panel shows the RMSD density distribution for each complex, highlighting the consistency of the structural stability. (<b>B</b>) Cluster analysis results with structural superposition of <b>MB-6a</b> conformations throughout the MD simulation. Numbers indicate distinct conformational clusters, with the predominant cluster representing 100%, 99.99%, 88.00%, and 75.61% of the simulation time for <b>MB-6a</b>-A, <b>MB-6a</b>-B, <b>MB-6a</b>-C, and <b>MB-6a</b>-D, respectively. The high percentage of the predominant cluster for each <b>MB-6a</b> molecule indicates stable binding modes with minimal conformational variations.</p>
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<p>Clustering results of the molecular dynamics simulation. Both axes represent simulation time in ps. The clustering analysis compares simulation frames, grouping similar poses of the ligand pocket region. Cluster analysis was performed for complexes A<sub>PKM2</sub>-<b>MB-6a</b>-A (<b>A</b>), B<sub>PKM2</sub>-<b>MB-6a</b>-B (<b>B</b>), and D<sub>PKM2</sub>-<b>MB-6a</b>-D (<b>C</b>), considering a 2 Å binning using the gromos algorithm. The graphs represent the root mean square deviation (RMSD) matrix on the upper left, and respective clusters plotted throughout 300 ns on the bottom right. Cluster indices are indicated by different colors.</p>
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<p>Energetic analysis of PKM2-<b>MB-6a</b> binding. (<b>A</b>) Time evolution of MMPBSA energy (kcal/mol) during the last 100 ns of MD simulation. (<b>B</b>–<b>D</b>) Per-residue energy decomposition analysis showing the contribution of individual residues to the total binding energy for A<sub>PKM2</sub>-<b>MB-6a</b>-A (<b>B</b>), B<sub>PKM2</sub>-<b>MB-6a</b>-B (<b>C</b>), and D<sub>PKM2</sub>-<b>MB-6a</b>-D (<b>D</b>). Negative values indicate favorable contributions to binding, while positive values represent unfavorable contributions.</p>
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<p>The 2D and 3D interaction diagrams of PKM2-<b>MB-6a</b> complexes from the last frame of MD simulation. (<b>A</b>) Three-dimensional representation showing the binding mode of <b>MB-6a</b> compounds in different chains of PKM2. Hydrogen bonds are highlighted with blue lines, halogen bonds with green lines, and hydrophobic contacts with dashed lines. Key interacting residues are labeled and shown as sticks. The interactions are highlighted in different boxes: <b>MB-6a</b>-A interacting with A<sub>PKM2</sub> (blue box), <b>MB-6a</b>-B interacting with B<sub>PKM2</sub> (red box), and <b>MB-6a</b>-D interacting with D<sub>PKM2</sub> (green box). (<b>B</b>) Two-dimensional interaction diagrams showing the binding mode of <b>MB-6a</b> with chains A, B, and D of PKM2. Residues are colored according to their type: negatively charged (orange), positively charged (blue), polar (light blue), and hydrophobic (light green). Different types of interactions are represented by distinct line styles: hydrogen bonds (blue arrows), halogen bonds (red arrows), and π-π stacking (green lines). Grey circles indicate solvent exposure. The <b>MB-6a</b> structure is shown in the center of each diagram, with key interaction features highlighted.</p>
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18 pages, 7153 KiB  
Article
Bacterial Outer Membrane Vesicle (OMV)-Encapsulated TiO2 Nanoparticles: A Dual-Action Strategy for Enhanced Radiotherapy and Immunomodulation in Oral Cancer Treatment
by Shun-An Kan, Li-Wen Zhang, Yu-Chi Wang, Cheng-Yu Chiang, Mei-Hsiu Chen, Shih-Hao Huang, Ming-Hong Chen and Tse-Ying Liu
Nanomaterials 2024, 14(24), 2045; https://doi.org/10.3390/nano14242045 - 20 Dec 2024
Viewed by 424
Abstract
Oral squamous-cell carcinoma (OSCC) poses significant treatment challenges due to its high recurrence rates and the limitations of current therapies. Titanium dioxide (TiO2) nanoparticles are promising radiosensitizers, while bacterial outer membrane vesicles (OMVs) are known for their immunomodulatory properties. This study [...] Read more.
Oral squamous-cell carcinoma (OSCC) poses significant treatment challenges due to its high recurrence rates and the limitations of current therapies. Titanium dioxide (TiO2) nanoparticles are promising radiosensitizers, while bacterial outer membrane vesicles (OMVs) are known for their immunomodulatory properties. This study investigates the potential of OMV-encapsulated TiO2 nanoparticles (TiO2@OMV) to combine these effects for improved OSCC treatment. TiO2 nanoparticles were synthesized using a hydrothermal method and encapsulated within OMVs derived from Escherichia coli. The TiO2@OMV carriers were evaluated for their ability to enhance radiosensitivity and stimulate immune responses in OSCC cell lines. Reactive oxygen species (ROS) production, macrophage recruitment, and selective cytotoxicity toward cancer cells were assessed. TiO2@OMV demonstrated significant radiosensitization and immune activation compared to unencapsulated TiO2 nanoparticles. The system selectively induced cytotoxicity in OSCC cells, sparing normal cells, and enhanced ROS generation and macrophage-mediated antitumor responses. This study highlights TiO2@OMV as a dual-action therapeutic platform that synergizes radiotherapy and immunomodulation, offering a targeted and effective strategy for OSCC treatment. The approach could improve therapeutic outcomes and reduce the adverse effects associated with conventional therapies. Full article
(This article belongs to the Section Biology and Medicines)
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<p>(<b>a</b>) TEM images of the TiO<sub>2</sub> NPs synthesized by TB/OA/OM = 1:6:4 molar ratio, the formation of spherical particles of TiO<sub>2</sub> NPs with an average size of 2–5 nm. (<b>b</b>) SEM images of the TiO<sub>2</sub> NPs with an aggregated spherical structure. (<b>c</b>) EDX of the TiO<sub>2</sub> NPs, showing the composition of carbon (C), oxygen (O), and titanium (Ti) elements. (<b>d</b>) XRD of the TiO<sub>2</sub> NPs.</p>
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<p>Preparation and characterization of DH5-α outer membrane-coated nanoparticles (TiO<sub>2</sub>@OMV NPs). TEM images of (<b>a</b>) OMV NPs, (<b>b</b>) bare TiO<sub>2</sub>, and (<b>c</b>) TiO<sub>2</sub>@OMV NPs. (<b>a</b>,<b>c</b>) Samples were negatively stained with phosphotungstic acid before imaging.</p>
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<p>(<b>a</b>) Cell viability using PrestoBlue Cell Viability Reagent for CAL27 and L929 cells exposed to OMV at different concentrations (0, 0.1, 2, 5, 10 μg/mL) at 24 h. (<b>b</b>) Cell viability using PrestoBlue Cell Viability Reagent for CAL27 and L929 cells exposed to TiO<sub>2</sub>@OMV nanoparticles at different concentrations (0, 0.1, 2, 5,10 μg/mL) at 24 h. The results are expressed as mean ± standard deviation (SD) of n = 3 biologically independent samples. Statistical analysis was performed using two-way ANOVA.</p>
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<p>Fluorescence microscopic images of the localization of TiO<sub>2</sub>@OMV nanoparticle uptake in (<b>a</b>) CAL27 cells and (<b>b</b>) L929 cells treated with TiO<sub>2</sub>@OMV nanoparticle for 0, 3, 12, and 24 h. TiO<sub>2</sub>@OMV nanoparticle concentration: 10 μg/mL (TiO<sub>2</sub>@OMV NPs were labeled with vibrant DiD (red) fluorescence). Nucleuses were labeled with vibrant DAPI (blue) fluorescence. Actin was labeled with phalloidin (green) fluorescence. (<b>c</b>) The statistics of cell uptake with MetaMorphsoftware 7.10.4. Representative images were taken by a Leica fluorescence microscope at a magnification of 20× (Scale bar = 50 μm).</p>
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<p>The effects of TiO<sub>2</sub>@OMV nanoparticles on cell cycle distribution and apoptosis. (<b>a</b>) CAL27 and L929 cells were treated with media containing 0, 5, 7.5, and 10 μg/mL TiO<sub>2</sub>@OMV nanoparticles. After 24 h, the cells were harvested and fixed in ice alcohol. Then, the cells were incubated in PBS containing 40 μg/mL propidium iodide and 100 μg/mL RNase A. Propidiumiodide-labeled nuclei were analyzed by flow cytometry. (<b>b</b>) The statistics of CAL27 cell cycle. (<b>c</b>) The statistics of CAL27 apoptosis. (<b>d</b>) The statistics of L929 cell cycle. (<b>e</b>) The statistics of L929 apoptosis.</p>
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<p>The generation of ROS from TiO<sub>2</sub>@OMV, detected by DCFDA after being exposed to a 6 MeV X-ray beam at radiation doses of 2 Gy (excitation: 485 nm and emission: 535 nm). The results are expressed as mean ± standard deviation (SD) of n = 3 biologically independent samples. Statistical analysis was performed using two-way ANOVA.</p>
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<p>Cell viability of (<b>a</b>) CAL27 oral cancer cells, and (<b>b</b>) L929 normal cells incubated with TiO<sub>2</sub>@OMV nanoparticles (various concentrations = 0, 0.1, 2, 5, 10 μg/mL) for 12 h and subjected to X-ray irradiation (6 MV, 2 Gy) or no irradiation. The results are expressed as mean ± standard deviation (SD) of n = 3 biologically independent samples. Statistical analysis was performed using two-way ANOVA **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>(<b>a</b>) Macrophage migration was analyzed 24 h after counterstaining cells in the lower chamber with DAPI. Representative images were taken by a Leica fluorescence microscope at a magnification of 20× (Scale bar = 50 μm). (<b>b</b>) The statistics of red fluorescent macrophages seeded to bottom chambers. (<b>c</b>) The presentation of the macrophage–cancer cell co-culture set up in transwell plates (the 3 μm microporous membrane allows for the migration of macrophages). DiD-labeled macrophages were seeded onto the insert and CAL27 cancer cells were seeded onto the bottom chamber. Cancer cells treated with OMVs (5 ug/mL) and TiO<sub>2</sub>@OMV (5 ug/mL) for 12 h and were subjected to X-ray irradiation (6 MV, 2 Gy) or no irradiation.</p>
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<p>The cell viability of the macrophage–cancer cell co-culture set up in transwell plates (0.4 μm microporous membrane). Macrophages were seeded onto the insert and CAL27 cancer cells were seeded onto the bottom chamber. Cancer cells treated with OMVs (5 ug/mL) and TiO<sub>2</sub>@OMV (5 ug/mL) for 12 h and were subjected to X-ray irradiation (6 MV, 2 Gy) or no irradiation. The results are expressed as mean ± standard deviation (SD) of n = 3 biologically independent samples. Statistical analysis was performed using two-way ANOVA.</p>
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<p>Cytokine levels of CAL27 cells medium. Macrophage–cancer cell co-culture and cancer cells treated with OMVs (5 ug/mL) and TiO<sub>2</sub>@OMV (5 ug/mL) for 12 h and were subjected to X-ray irradiation (6 MV, 2 Gy) or no irradiation. After two days, the ELISA kit analysis (<b>a</b>) of TNF-α Cytokine levels. (<b>b</b>) IL-6 Cytokine levels.</p>
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7 pages, 2490 KiB  
Case Report
Diagnostic Application of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Treatment of Oral Squamous Cell Carcinoma in an African Pygmy Hedgehog
by Jaegyeong Shin, Nari Kim, Gwi-Ho Jeon, Taesik Yun, Byeong-Teck Kang and Dong-Hyuk Jeong
Animals 2024, 14(24), 3679; https://doi.org/10.3390/ani14243679 - 20 Dec 2024
Viewed by 285
Abstract
Neoplastic diseases are common in African pygmy hedgehogs (Atelerix albiventris), with squamous cell carcinoma (SCC) being the most prevalent oral tumor. Traditional imaging techniques like computed tomography (CT) have limitations in accurately defining tumor extent and detecting metastasis. In this study, [...] Read more.
Neoplastic diseases are common in African pygmy hedgehogs (Atelerix albiventris), with squamous cell carcinoma (SCC) being the most prevalent oral tumor. Traditional imaging techniques like computed tomography (CT) have limitations in accurately defining tumor extent and detecting metastasis. In this study, a hedgehog with a suspected oral tumor underwent 18F-FDG PET/CT imaging, revealing a hypermetabolic lesion consistent with SCC and indications of metastatic activity. The lesion was too extensive for a lumpectomy, and suspected metastasis led to the decision for euthanasia due to the impracticability of further treatment. A histopathological examination after autopsy confirmed the diagnosis and metastatic spread, as suggested by PET/CT findings. This is the first case report demonstrating the potential use of 18F-FDG PET/CT in hedgehogs, facilitating the accurate staging and management of oral SCC. Further research is needed to establish PET/CT as a standard diagnostic tool for neoplastic diseases in hedgehogs. Full article
(This article belongs to the Special Issue Wildlife Diseases: Pathology and Diagnostic Investigation)
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<p>FDG-PET findings in a hedgehog (<span class="html-italic">Atelerix albiventris</span>) in the pulmonary region. Pre-contrast CT image (<b>a</b>), post-contrast CT image (<b>b</b>), FDG-PET (<b>c</b>), and PET/CT fusion (<b>d</b>) images. Pre-contrast CT image (<b>a</b>) showing anatomical structures without enhancement. Post-contrast CT image (<b>b</b>) demonstrating enhanced anatomical structures. FDG-PET image (<b>c</b>), where low and high FDG uptakes are represented by blackish and whitish colors. Fused FDG-PET/CT image (<b>d</b>) using a hot metal color scale, where low and high FDG uptakes are represented by blackish-to-reddish and yellowish colors. CT, computed tomography; FDG, 18F-fluorodeoxyglucose; PET, positron emission tomography.</p>
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<p>Necropsy and FDG-PET findings in a hedgehog (<span class="html-italic">Atelerix albiventris</span>) with an oral tumor. (<b>a</b>) An oral mass (arrows) found in the left maxillary region. FDG-PET (<b>b</b>) and PET/CT fusion (<b>c</b>) images. High FDG uptake is observed in the tumor lesion (arrows), and the maximal SUV of the lesion is 10.31.</p>
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<p>Photomicrographs of histopathological evaluation in oral (<b>a</b>,<b>b</b>) and lung (<b>c</b>) tissue of a hedgehog (<span class="html-italic">Atelerix albiventris</span>) with SCC. (<b>a</b>) Oral tissue: tumorous epithelial proliferation with nuclear pleomorphism and mitotic figures. Hematoxylin and eosin (H&amp;E) stain. Scale bar = 50 μm. (<b>b</b>) Oral tissue: stratified squamous epithelial cells with a keratin pearl (asterisk). H&amp;E stain. Scale bar = 100 μm. (<b>c</b>) Lung tissue: pulmonary edema and metastatic squamous cell carcinoma with inflammatory cell infiltration. H&amp;E stain. Scale bar = 50 μm.</p>
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21 pages, 725 KiB  
Review
Metabolomic Profiling of Oral Potentially Malignant Disorders and Its Clinical Values
by Nur Fatinazwa Mohd Faizal, Vui King Vincent-Chong, Anand Ramanathan, Ian C. Paterson, Lee Peng Karen-Ng and Zuraiza Mohamad Zaini
Biomedicines 2024, 12(12), 2899; https://doi.org/10.3390/biomedicines12122899 - 19 Dec 2024
Viewed by 523
Abstract
Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, [...] Read more.
Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, and non-dysplastic lesions may also undergo malignant transformation. Oral carcinogenesis is a complex molecular process that involves somatic alterations and the deregulation of transcriptions, protein expression, and metabolite levels. Metabolomics, which is the scientific study of metabolites, has emerged as a promising high-throughput approach to investigate the metabolic changes of small molecules in biological pathways. In this review, we summarize the data relating to the metabolomic profiling of OPMDs, which will help elucidate the complex process of oral carcinogenesis. Furthermore, we identify that among all metabolites, citrate, pyruvate, and glutamate may serve as potential biomarkers for oral leukoplakia (OLK). Notably, metformin and gluconate have been shown to target glutamate and citrate, respectively, in cancer cells. Based on these findings, we propose that targeting these metabolites in patients with OPMD could be a promising therapeutic strategy to mitigate OPMD progression and potentially reduce the risk of malignant transformation. We also discuss the limitations and future directions of metabolomics in OPMD. Understanding these important metabolites is crucial for early detection and monitoring of oral cancer progression. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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<p>Metabolomic profiling workflow from sample collection through to data analysis, illustrating each stage from sample preparation, metabolite extraction, and detection to data processing and interpretation.</p>
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<p>This diagram displays the metabolomic pathways and their related metabolites associated with oral leukoplakia.</p>
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14 pages, 949 KiB  
Article
The Prognostic Value of Preoperative Total Cholesterol in Surgically Treated Oral Cavity Cancer
by Yao-Te Tsai, Ming-Hsien Tsai, Adarsh Kudva, Andrea De Vito, Chia-Hsuan Lai, Chun-Ta Liao, Chung-Jan Kang, Yuan-Hsiung Tsai, Cheng-Ming Hsu, Ethan I. Huang, Geng-He Chang, Ming-Shao Tsai and Ku-Hao Fang
Biomedicines 2024, 12(12), 2898; https://doi.org/10.3390/biomedicines12122898 - 19 Dec 2024
Viewed by 410
Abstract
Background: With growing evidence linking lipid profile changes to tumor development and cancer prognosis, we investigated the prognostic significance of preoperative serum total cholesterol (TC) levels in patients with oral cavity squamous cell carcinoma (OSCC) undergoing surgical treatment. Methods: We conducted a retrospective [...] Read more.
Background: With growing evidence linking lipid profile changes to tumor development and cancer prognosis, we investigated the prognostic significance of preoperative serum total cholesterol (TC) levels in patients with oral cavity squamous cell carcinoma (OSCC) undergoing surgical treatment. Methods: We conducted a retrospective observational study involving 310 patients with primary OSCC who received surgery at our hospital from January 2009 to December 2018. Receiver operating characteristic curve analysis was performed to determine the optimal preoperative TC cutoff value, with the Youden Index employed as the optimization criterion to maximize the sum of sensitivity and specificity. Variables with p < 0.1 in the univariable analysis were included in the multivariable Cox regression model, and stepwise selection was used to identify the optimal subset of prognostic factors for overall survival (OS) and disease-free survival (DFS). Results: An optimal TC cutoff of 157 mg/dL was established. Patients with TC < 157 mg/dL exhibited significantly lower 5-year rates of OS and DFS (p < 0.001 and p = 0.006, respectively). Multivariable analysis confirmed that TC < 157 mg/dL represented an independent prognostic factor for reduced OS and DFS rates. Subgroup analyses reinforced the consistent prognostic significance of TC. We also constructed a nomogram (concordance index: 0.74) to provide personalized OS predictions, enhancing the clinical utility of TC. Conclusions: Preoperative TC appears to be a significant prognostic factor for OS and DFS after OSCC surgery. Routine TC assessment facilitates the development of nomograms for personalized survival predictions, supports clinicians in tailoring treatment strategies, and guides nutritional or metabolic interventions to enhance patient outcomes. Further multicenter prospective studies are needed to validate our findings. Full article
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<p>Optimal TC cutoff value, as derived via executing receiver operating characteristic curve analysis. Abbreviation: TC, total cholesterol.</p>
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<p>Kaplan–Meier curves for (<b>a</b>) overall survival and (<b>b</b>) disease-free survival, stratified by preoperative TC cutoff. Abbreviation: TC, total cholesterol.</p>
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<p>Subgroup analysis assessing the discriminatory capacity of TC for overall survival. Abbreviations: CI, confidence interval; DOI, depth of invasion; ENE, extranodal extension; HR, hazard ratio; PNI, perineural invasion; T-cholesterol, total cholesterol.</p>
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<p>Nomogram for predicting overall survival. (<b>a</b>) Multivariable-analysis-derived independent prognostic factors were used to construct a nomogram for predicting overall survival. The contribution of each variable’s risk is illustrated by the length of its line segment and its corresponding points. The total points were derived by summing the points assigned to each individual variable. The line extending from the calculated total points indicates the overall survival probabilities at 3 years and 5 years. Calibration plots were generated for (<b>b</b>) 3-year and (<b>c</b>) 5-year overall survival rates. The gray 45° line signifies perfectly accurate overall survival predictions, and the blue line represents the actual nomogram-derived predictions. The nomogram’s performance and the 95% confidence intervals for overall survival predictions are illustrated using blue dots and bars, respectively. Abbreviations: LVI, lymphovascular invasion; M–D, moderately differentiated; P–D, poorly differentiated; TC, total cholesterol; W–D, well differentiated.</p>
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13 pages, 1826 KiB  
Article
Prognostic Utility of the Modified Systemic Inflammation Score for Patients Undergoing Oral Cavity Cancer Surgery
by Ku-Hao Fang, Sheng-Wei Lo, Adarsh Kudva, Andrea De Vito, Yuan-Hsiung Tsai, Cheng-Ming Hsu, Geng-He Chang, Ethan I. Huang, Ming-Shao Tsai, Chia-Hsuan Lai, Ming-Hsien Tsai, Chun-Ta Liao, Chung-Jan Kang and Yao-Te Tsai
Diagnostics 2024, 14(24), 2856; https://doi.org/10.3390/diagnostics14242856 - 19 Dec 2024
Viewed by 356
Abstract
Background/Objectives: Chronic inflammation significantly contributes to human malignancies. We investigated the prognostic significance of the preoperative modified systemic inflammation score (mSIS) in patients with primary oral cavity squamous cell carcinoma (OCSCC). Methods: We retrospectively reviewed data from 320 OCSCC patients who underwent curative [...] Read more.
Background/Objectives: Chronic inflammation significantly contributes to human malignancies. We investigated the prognostic significance of the preoperative modified systemic inflammation score (mSIS) in patients with primary oral cavity squamous cell carcinoma (OCSCC). Methods: We retrospectively reviewed data from 320 OCSCC patients who underwent curative surgery between 2007 and 2017. Based on preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin levels, patients were classified into three groups: mSIS = 2 (LMR < 3.4 and albumin < 4.0 g/dL), mSIS = 1 (LMR < 3.4 or albumin < 4.0 g/dL), and mSIS = 0 (LMR ≥ 3.4 and albumin ≥ 4.0 g/dL). We explored the associations between the preoperative mSIS and overall survival (OS) and disease-free survival (DFS). We developed a nomogram based on mSIS for OS prediction. Results: The distribution was mSIS = 0 (n = 197, 61.6%), mSIS = 1 (n = 99, 30.9%), and mSIS = 2 (n = 24, 7.5%). Kaplan–Meier estimated OS and DFS for the mSIS = 0, mSIS = 1, and mSIS = 2 groups demonstrated a sequential decrease (both p < 0.001). The prognostic significance of mSIS was consistent across subgroup analyses. Multivariable analysis revealed that mSIS = 1 and mSIS = 2 were independent negative prognostic indicators. The mSIS-based nomogram effectively predicted OS (concordance index: 0.755). Conclusions: The mSIS reliably predicts OS and DFS in OCSCC patients undergoing surgery, with the nomogram providing individualized OS estimates, enhancing mSIS’s clinical utility. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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<p>Survival analysis (<b>A</b>) Kaplan–Meier overall survival curves for each mSIS group (<span class="html-italic">p</span> &lt; 0.001), (<b>B</b>) Kaplan–Meier disease-free survival curves for each mSIS group (<span class="html-italic">p</span> &lt; 0.001). Abbreviation: mSIS, modified systemic inflammation score.</p>
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<p>Subgroup analysis of the discriminative ability of mSIS for overall survival. Abbreviations: CI, confidence interval; DOI, depth of invasion; ENE, extranodal extension; HR, hazard ratio; mSIS, modified systemic inflammation score; PNI, perineural invasion.</p>
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<p>Overall survival curves based on preoperative mSIS in (<b>A</b>) patients who received surgery alone (<span class="html-italic">p</span> = 0.008), (<b>B</b>) patients who received surgery and adjuvant therapy (<span class="html-italic">p</span> &lt; 0.001), and (<b>C</b>) patients with stage III–IV disease (<span class="html-italic">p</span> &lt; 0.001). Disease-free survival curves based on preoperative mSIS in (<b>D</b>) patients who received surgery alone (<span class="html-italic">p</span> = 0.011), (<b>E</b>) patients who received surgery and adjuvant therapy (<span class="html-italic">p</span> &lt; 0.001), and (<b>F</b>) patients with stage III–IV disease (<span class="html-italic">p</span> &lt; 0.001). Abbreviations: mSIS, modified systemic inflammation score.</p>
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<p>Nomogram for predicting overall survival. (<b>A</b>) Independent prognostic factors identified in multivariable analysis are incorporated into the nomogram. Each parameter’s risk contribution is represented by a line segment with corresponding uppermost points. Total points are calculated by summing the points for each parameter. To estimate the likelihood of 3-year and 5-year OS, draw a vertical line downward from the total points. (<b>B</b>) Calibration plot for 3-year OS. (<b>C</b>) Calibration plot for 5-year OS. An ideal OS prediction is represented by a 45° line, while the nomogram’s predictions are illustrated by a blue line. Predictive performance and 95% confidence intervals are represented by blue dots and bars, respectively. Abbreviations: LVI, lymphovascular invasion; mSIS, modified systemic inflammation score; PNI, perineural invasion.</p>
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8 pages, 2828 KiB  
Article
A Novel Reconstruction Approach After Skin Cancer Ablation Using Lateral Arm Free Flap: A Serial Case Report
by Soyeon Jung, Seungjun Lee and Seokchan Eun
Medicina 2024, 60(12), 2082; https://doi.org/10.3390/medicina60122082 - 19 Dec 2024
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Abstract
Background and Objectives: The lateral arm flap has been a very useful choice for the reconstruction of small to medium-sized defects, such as in the hands, extremities, and oral head and neck area. Its versatile characteristics and surgical feasibility allow this flap [...] Read more.
Background and Objectives: The lateral arm flap has been a very useful choice for the reconstruction of small to medium-sized defects, such as in the hands, extremities, and oral head and neck area. Its versatile characteristics and surgical feasibility allow this flap to be widely applied, but its reconstructive potential in the facial subunit after tumor ablation procedures has never been reported. In this study, we aimed to utilize the advantages of this flap to carry out facial temple subunit defect reconstruction. Materials and Methods: Between 2020 and 2023, 12 patients underwent temple reconstruction with lateral arm free flaps after wide malignant tumor excisions. There were seven women and five men, and the mean patient age was 60.6 years. Among the patients with cancer, six had squamous cell carcinoma, five had basal cell carcinoma, and one had myxofibrosarcoma. All flaps were elevated under general anesthesia. Alprostadil (PGE1, Eglandin®, Mitsubishi Tanabe Korea, Seoul, Republic of Korea) was administered postoperatively. Results: All flaps were the fasciocutaneous type, with sizes that varied from 3 cm × 4 cm to 5 cm × 7 cm (average size: 22.7 cm2). The average pedicle length was 6.1 cm. The versatility of the lateral arm flap enabled successful coverage in all cases, with no specific complications. Good functional outcomes and good ranges of motion in the donor arms were observed after surgery. Conclusions: The authors successfully verified the advantages of lateral arm flaps in the treatment of medium-sized facial temple subunit defects. Full article
(This article belongs to the Special Issue New Developments in Plastic Surgery)
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<p>A case of a patient with left temple squamous cell carcinoma. (<b>A</b>) A preoperative photograph. (<b>B</b>) The 4 cm × 6 cm defect after wide excision. (<b>C</b>) A photo taken immediately after reconstruction with a lateral arm flap. (<b>D</b>) A photo taken 18 months after the operation. (<b>E</b>) The primarily closed donor site.</p>
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<p>A case of a patient with right temple squamous cell carcinoma. (<b>A</b>) A preoperative photo. (<b>B</b>) Photos taken immediately after flap donor site closure and (<b>C</b>) reconstruction with a 5 cm × 3 cm lateral arm flap. (<b>D</b>) A photo taken 8 months after the operation.</p>
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<p>A case of a patient with left temple myxofibrosarcoma. (<b>A</b>) A preoperative photo. (<b>B</b>) A photo showing skin markings for a wide excision. (<b>C</b>) A photo taken immediately after tumor excision and recipient preparation. (<b>D</b>) The harvested 4 cm × 6 cm lateral arm flap. (<b>E</b>) A photo taken 22 months after the operation. (<b>F</b>) A photograph of the donor site, one month after the surgery.</p>
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<p>A case of a patient with left temple squamous cell carcinoma. (<b>A</b>) A preoperative photo. (<b>B</b>) The design of the 4 cm × 4.5 cm lateral arm flap. (<b>C</b>) Only the septal branch was included in the flap. (<b>D</b>) Preservation of the posterior antebrachial cutaneous nerve (PABCN). (<b>E</b>) A photo taken 19 months after the operation. (<b>F</b>) A postoperative view of the donor site, 19 months after the surgery.</p>
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<p>A case of a patient with right temple basal cell carcinoma. (<b>A</b>) A preoperative photo. (<b>B</b>) A photo taken after tumor resection and the preparation of the recipient superficial temporal vessels. (<b>C</b>) The design of the 3 cm × 4 cm lateral arm flap. (<b>D</b>) A photo taken 18 months after the operation (<b>E</b>) An intraoperative view of the harvested lateral arm flap preserving the septal branch of the PABCN with a sufficient vascular pedicle length. (<b>F</b>) A photograph of the donor site primarily closed.</p>
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Article
Impact of Face Mask-Wearing on Quality of Life in Post-Surgical Oral Cancer Patients: A Cross-Sectional Study
by Romain Lan, Frédéric Silvestri, Maryem Rhanoui, Cassandre Bezier, Nicolas Fakhry, Florence Carrouel and Chloé Mense
Cancers 2024, 16(24), 4199; https://doi.org/10.3390/cancers16244199 - 17 Dec 2024
Viewed by 378
Abstract
Background: Treatments for oral squamous cell carcinomas (OSCCs) often result in significant aesthetic and functional issues, impacting patients’ quality of life (QoL). The COVID-19 pandemic’s mask mandates may have provided psychosocial benefits by concealing facial disfigurements, potentially reducing stigma. This study aimed to [...] Read more.
Background: Treatments for oral squamous cell carcinomas (OSCCs) often result in significant aesthetic and functional issues, impacting patients’ quality of life (QoL). The COVID-19 pandemic’s mask mandates may have provided psychosocial benefits by concealing facial disfigurements, potentially reducing stigma. This study aimed to assess the impact of mask-wearing on the QoL of patients surgically treated for OSCC. Methods: This single-center, cross-sectional study, conducted from June 2022 to December 2023, included patients who had completed their treatment and returned home before or during the mask-wearing mandate. They answered a questionnaire using a four-point Likert scale to evaluate the mask-wearing’s impact on QoL and the influence on it of physical appearance, tumor localization, radiotherapy, and treatment end date. Results: The questionnaire analysis found a high internal consistency among the questions (Cronbach’s alpha = 0.931). Considering 41 patients (median age 69, 63% male), wearing a mask significantly improved QoL, with a mean score of 1.66 compared to a score of 2.00 for patients not wearing it (p < 0.001). This improvement was particularly notable for appearance concerns, fear of perception by family or others, and sociability apprehension. The QoL, with or without mask use, was not significantly modified when considering physical appearance, tumor localization, radiotherapy, or end date of the treatment, as demonstrated by two-way ANOVA tests and multiple linear regression. Conclusions: Mask-wearing positively impacted QoL in OSCC patients, providing psychological relief from disfigurement and social stigma. Masks offer a simple, accessible solution to enhance QoL while awaiting a definitive prosthetic treatment, suggesting that their continued use could be beneficial in supportive care strategies. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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<p>(<b>A</b>). Box plot of overall mean scores for the “with” and “without mask” conditions; (<b>B</b>). line plot of mean scores for each question, with significant <span class="html-italic">p</span>-values for Q1, Q2, Q3, Q4, and Q9.</p>
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<p>Box plot distribution of scores for the “with” and “without mask” conditions according to physical appearance, initial tumor location, radiotherapy, and date of end of treatment.</p>
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<p>Heatmap of the correlation based on the mixed-effects model regression analyzing the relationships between the categories. The color intensity represents the magnitude and direction of the coefficients (blue for negative, and red for positive).</p>
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<p>Bar plots of mixed-effects model coefficients illustrating the impact of categorical predictors on the responses to the 9 self-perception questions, separated by mask condition (“without mask” and “with mask”). Each bar represents the coefficient’s magnitude and direction, with positive values indicating an increase in the response score, and negative values indicating a decrease.</p>
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