An Update on the Use of Artificial Intelligence in Digital Pathology for Oral Epithelial Dysplasia Research.

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.

Performance of AI chatbots on controversial topics in oral medicine, pathology, and radiology.

OBJECTIVES: In this study, we assessed 6 different artificial intelligence (AI) chatbots (Bing, GPT-3.5, GPT-4, Google Bard, Claude, Sage) responses to controversial and difficult questions in oral pathology, oral medicine, and oral radiology. STUDY DESIGN: The chatbots' answers were evaluated by board-certified specialists using a modified version of the global quality score on a 5-point Likert scale. The quality and validity of chatbot citations were evaluated. RESULTS: Claude had the highest mean score of 4.341 ± 0.582 for oral pathology and medicine. Bing had the lowest scores of 3.447 ± 0.566. In oral radiology, GPT-4 had the highest mean score of 3.621 ± 1.009 and Bing the lowest score of 2.379 ± 0.978. GPT-4 achieved the highest mean score of 4.066 ± 0.825 for performance across all disciplines. 82 out of 349 (23.50%) of generated citations from chatbots were fake. CONCLUSIONS: The most superior chatbot in providing high-quality information for controversial topics in various dental disciplines was GPT-4. Although the majority of chatbots performed well, it is suggested that developers of AI medical chatbots incorporate scientific citation authenticators to validate the outputted citations given the relatively high number of fabricated citations.

Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples. Through iterative training, the generator allows the creation of images that are indistinguishable from real ones, leading to high-quality image generation. Considering their success in computer vision, GANs hold great potential for medical diagnostic applications. In the medical field, GANs can generate images of rare diseases, aid in learning, and be used as visualization tools. GANs can leverage unlabeled medical images, which are large in size, numerous in quantity, and challenging to annotate manually. GANs have demonstrated remarkable capabilities in image synthesis and have the potential to significantly impact digital histopathology. This review article focuses on the emerging use of GANs in digital histopathology, examining their applications and potential challenges. Histopathology plays a crucial role in disease diagnosis, and GANs can contribute by generating realistic microscopic images. However, ethical considerations arise because of the reliance on synthetic or pseudogenerated images. Therefore, the manuscript also explores the current limitations and highlights the ethical considerations associated with the use of this technology. In conclusion, digital histopathology has seen an emerging use of GANs for image enhancement, such as color (stain) normalization, virtual staining, and ink/marker removal. GANs offer significant potential in transforming digital pathology when applied to specific and narrow tasks (preprocessing enhancements). Evaluating data quality, addressing biases, protecting privacy, ensuring accountability and transparency, and developing regulation are imperative to ensure the ethical application of GANs.

Corrigendum to "The Role of Medications in Causing Dry Eye".

[This corrects the article DOI: 10.1155/2012/285851.].

Oral squamous cell carcinoma: early detection and improved 5-year survival in 102 patients.

The 5-year survival rate for oral cancer remains poor, as a significant number of patients present with advanced disease at the time of diagnosis. The need remains for early detection within the context of routine oral examinations and evaluation of any noted clinical abnormalities. This retrospective study analyzed patient demographics, lesion characteristics, and 5-year survival rates associated with oral squamous cell carcinoma (OSCC) that was initially assessed using computer-assisted, 3-dimensional analysis of a transepithelial oral brush biopsy. Patients with oral lesions were initially assessed by community-based dentists and physicians using an oral brush biopsy. In 102 patients, OSCC was subsequently confirmed by incisional biopsy and histopathologic analysis. The majority of patients were without traditional risk factors. Almost half of the cancers presented as white lesions, and one-third presented as lesions smaller than 5 mm. In about three-fourths of all cases, OSCC initially presented without pain or bleeding. The overall 5-year survival rate for all patients was approximately 94%. Despite barriers to early detection, identification of early, asymptomatic OSCC with innocuous-appearing clinical features is achievable. This earlier detection can be expected to lead to a marked improvement in overall survival patterns.

Follicular dendritic cell sarcoma of the head and neck: Case report, literature review, and pooled analysis of 97 cases.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare lymphoid neoplasm presenting in the head and neck. There are no pooled analyses of head and neck FDCS cases in the English language literature. METHODS: A MEDLINE and PubMed review of cases from 1978 to February 2014 was performed. Demographics, clinicopathologic data, and outcomes were summarized. RESULTS: We presented 2 patients and analyzed 97 cases. The mean age was 42.7 years (SD = 16.3 years). Outcomes were available for 76 patients. Tumors ≤4 cm had better disease-free survival (63% vs 28% at 5 years; p = .0282). Locoregional recurrence was significantly less likely with surgery and radiation compared to surgery alone (15% vs 45%; p = .019) and in patients receiving a neck dissection (10% vs 43%; p = .046). CONCLUSION: This pooled analysis provides the largest sample size of FDCS of the head and neck to date and suggests that radiation and neck dissection may be beneficial to locoregional oncologic control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2241-E2249, 2016.

Oral mucosal precancer and cancer: A helpful discriminating clinical tool

The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clinician is a straightforward grading system as a starting point for office end clinic use for all patients

Oral mucosal precancer and cancer: A helpful discriminating clinical tool.

The authors have collaborated with many colleagues in several countries in formulating a useful and practical clinical tool for evaluating oral mucosal findings on routine examination. Consideration of several factors including history, evolution of positive findings and clinical information allows placement of examination results into one of three categories which are graded by a color scheme along a spectrum of concerns (green to red, or no concern to serious concern). Afforded to the clinician is a straightforward grading system as a starting point for office end clinic use for all patients.

Current management strategies for verrucous hyperkeratosis and verrucous carcinoma.

Proliferative verrucous leukoplakia, a lesion of unknown origin with no strictly defined diagnostic criteria, is worthy of great clinical concern and scrutiny. Treatment options vary, with no consensus regarding the most efficient and effective strategy. Further complicating the unusual biology and behavior of this lesion is its usual multifocal presentation and progression, with lifelong vigilance required after treatment. Verrucous carcinoma is a progressive lesion with high recurrence and 5-year survival rates. Surgery remains the preferred treatment. Further investigation into the combination of surgery and antiviral agents may bring additional improvement in patient care.

The role of medications in causing dry eye.

The purpose of this paper is to review the possible role of polypharmacy in causing dry eye disease (DED), reflecting the complex interactions and complications associated with the use of multiple systemic and topical ocular medications. The pharmacological, physiological, anatomical, and histological mechanisms causing dry mouth differ little from those causing dry eye. Oral polypharmacy is the most common cause of dry mouth, but has not been investigated as a cause of dry eye. Topical ocular polypharmacy has been shown to cause DED. Information on drugs that likely cause or aggravate DED and the controversial role of preservatives in topical ocular medications are examined. Systemic or topical ocular medications and preservatives used in topical ocular drugs may cause dry eye through the drug's therapeutic action, ocular surface effects, or preservatives, and the effects probably are additive. Long-term use of topical ocular medications, especially those containing preservatives such as BAK, may play an important role in DED and the role of polypharmacy needs further study. We review possible ways to decrease the risk of medication-related dry eye.

The effect of amifostine on submandibular gland histology after radiation.

Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degeneration, acinar degeneration, and inflammatory component presence. Results. Differences in gender, tumor stage, amifostine dose, age, number of days after neck dissection, and smoking history (pack years) exposure were not significant between the three groups, although there was a difference between groups in the primary subsite (P = 0.006). The nonparametric Cuzick's test for histologic parameters with varied amifostine treatment showed no significance among the three groups. Conclusions. Although patients did not receive a full dose of amifostine due to side effects, varying doses of amifostine had no apparent evident cytoprotective effects in three groups of cancer patients treated with primary chemoradiation.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Squamous Cell Carcinoma of the Oral Cavity and Oropharynx.

The most common malignancy to involve the oral cavity and oropharynx is squamous cell carcinoma (SCC). Because these oral cancers share an origin from the squamous epithelium, the pathology of oral SCC might be expected to be uniform and its diagnosis repetitive. In reality, the morphologic diversity in SCC, along with the propensity for reactive processes of the oral cavity to mimic SCC histologically, renders its diagnosis one of the more challenging in surgical pathology. This article discusses variants of oral and oropharyngeal SCC and highlights those features that help distinguish human papillomavirus-related from human papillomavirus-unrelated SCC.

Autoimmune oral mucosal diseases: clinical, etiologic, diagnostic, and treatment considerations.

This article discusses the classic autoimmune diseases: pemphigus vulgaris, mucosal pemphigoid, and oral lichen planus. These are generally considered of autoimmune origin or, at a minimum, immune system mediated. Cause, diagnosis, and treatment are discussed. As management of these diseases progresses, continued advances in molecular pathogenesis will allow insight into which strategies can be employed in interfering with the complex cascade of events leading to mucosal impairment and clinical morbidity.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected five systematic reviews and four clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Failure to diagnose and delayed diagnosis of cancer: medicolegal issues.

BACKGROUND: Failure to diagnose and delayed diagnosis of cancer can have a significant effect on patients' morbidity and mortality. Oral health care professionals should be alert for oral premalignant and malignant disease and head and neck involvement by malignant disease. These issues have patient care and medicolegal implications. CASE DESCRIPTION: To provide guidance to practitioners, the authors present a series of cases of oral and head and neck cancer that resulted in legal action. They chose the medicolegal cases to highlight dental professionals' potential legal liability and provide guidance in patient care. CLINICAL IMPLICATIONS: Clinicians need to obtain complete comprehensive histories, perform thorough head and neck and oral examinations and appreciate the importance of being vigilant for abnormalities that may lead to early detection of potentially malignant disease.

End of life considerations in the head and neck cancer patient.

Oral and head and neck cancer carries an associated death rate five years after diagnosis and treatment that is high, essentially at a 50% level. In association with the dying process and the transition to death is a wide array of issues and considerations including the physical and emotional needs of the patient as well as associated caregivers. At a point, the transition must be understood in terms of non-oncologic management considerations and the broader needs of the patient and their family and the caregivers. Psychosocial and spiritual needs are to be addressed as well as the necessary components of preparation for death as to make a "good death". Communicating the status of the terminally-ill patient to the patient themselves and their family when cure or remission is no longer possible and the consideration of hospice care, palliation and issues of grieving all contribute to considerations in overall management at the end of life.