Grade Dysplasia Research Articles

Malignant Transformation of Dysplastic Vocal Fold Lesions

The reported rates of malignant transformation of dysplastic laryngeal lesions are highly variable, as is time to malignant degeneration. To evaluate the rate of and time to malignant transformation of dysplastic laryngeal lesions based on the World Health Organization (WHO) dysplasia classification system. PubMed, MEDLINE, Embase, CINAHL, CENTRAL, and Cochrane Reviews were searched from the date of database inception to June 8, 2023. English-language articles assessing the rate of malignant transformation using the 2005 WHO dysplasia classification system were included in this systematic review and meta-analysis. The study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data extraction was performed by 2 independent investigators. Study quality was assessed using a validated quality tool. When possible, data were pooled using random-effects meta-analysis. The primary outcome measure was the malignant transformation rate in each laryngeal dysplasia category. Secondary outcome measure was the time interval over which malignant transformation had occurred. A total of 5585 records were screened, 61 full texts were assessed, and 18 retrospective cohort studies with 3243 participants were included in the final review. The weighted pooled mean malignant transformation rates of mildly, moderately, and severely dysplastic lesions were 10.9%, 23.3%, and 30.5%, respectively. Malignant transformation rate of nondysplastic laryngeal lesions was 4.5%. Moderately and severely dysplastic lesions had significantly higher odds of malignant transformation compared with mildly dysplastic lesions (moderate: odds ratio [OR], 2.90 [95% CI, 2.06-4.09]; I2 = 0%; severe: OR, 3.42 [95% CI, 2.11-5.52]; I2 = 40%). Lesions without dysplasia had a significantly lower odds of malignant transformation compared with lesions with mild dysplasia (OR, 0.48; 95% CI, 0.28-0.81; I2 = 0%). The overall mean time to malignant transformation was 28.8 months (range, 22.0-35.6 months) for all dysplasia grades. This systematic review and meta-analysis found that the rate of malignant transformation increased with the grade of laryngeal dysplasia. Moderately dysplastic lesions were more likely to undergo malignant degeneration compared with mildly dysplastic lesions.

Analysis of Co-expression of HSP 70 and BCL 2 in Oral Precancer and Cancer Patients Using Immunohistochemistry.

Understanding of molecular model of oral carcinogenesis has carried cancer chemotherapy far forward from conventional drug therapies. Small molecule inhibitors have gained acceptance as it has fewer adverse effects and also provide targeted drug therapy. The association of HSP 70 (Heat Shock Protein 70) and BCL 2 (B-cell lymphoma 2) proteins with oral precancer and cancer is already established. However, the complex interaction between these two proteins and how they affect each other's expression is still not understood completely. In our study, we aimed to correlate the expression of HSP 70 and BCL 2 with different histopathological grades of oral precancer and cancer tissue samples using tissue immunohistochemistry. Tissue samples were taken from a total of 250 patients (100 OPMDs and 150 OSCCs) and subjected to immunohistochemistry using anti-human mouse monoclonal antibodies to HSP70 and BCL2. Immunostaining was done, and the immunostaining intensity distribution (IID) index was calculated. Immunoreactivity scores for both HSP 70 and BCL 2 correlated with different grades of dysplasia. However, only HSP 70 had a statistically significant association (p=0.066). We also found that HSP 70 showed an inverse correlation, with higher expression majorly seen in well-differentiated OSCCs. Our study unveiled the HSP 70-BCL 2 interaction and provides insights about how this might affect drug designing and help overcome therapeutic lags. However, further studies are needed to provide a comprehensive review of such interactions among various small molecules.

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

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. 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. A total of 24studies 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. 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.

Quantitative assessment Cyclooxygenase – 2 immunohistochemical expression in different grades of oral epithelial dysplasia

Oral leukoplakia (OLP) is one the most common potentially malignant disorders account 0.2 to 4.9% of malignant transformation and dysplastic lesions vary from 3-6% this rate of malignant conversion depends on the different grades of epithelial dysplasia. Recent literature suggests that increased levels of COX-2 in potentially malignant disorders and malignant tumors show prominent genetic evidence in tumorigenesis. Assessment of Cyclooxygenase-2 – 2 (COX-2) immunohistochemical expression in different grades of oral epithelial dysplasia. Materials and Methodology A total of forty formalin-fixed, paraffin-embedded tissue blocks were obtained from departmental archives which are histopathological diagnoses of different grades of oral epithelial dysplasia each grade ten samples was included. Stained with COX-2 and positive cells were counted and tabulated for statistical analysis. Results Comparison between genders in oral leukoplakia males was more when compared with females. The mean age in mild epithelial dysplasia was more when compared with moderate and severe epithelial dysplasia. Expression of COX-2 was increased from mild to severe epithelial dysplasia increases. The mean number of positive cells was increased. A comparison of all groups was not statistically significant (p≥0.05). Conclusion: Oral leukoplakia (OLP) is one the most common potentially malignant disorders which accounts for 0.2 to 4.9% of malignant transformation. COX-2 can be used for early detection and prognostic makers in different grades of oral epithelial dysplasia. Keywords: Cyclooxygenase, Expression, Oral leukoplakia, Potentially malignant transformation

Colorectal Polyps among Sudanese Patients: A Single-Center Experience (Eyes Study)

Introduction: A gastrointestinal polyp is an abnormal protrusion from the mucosal surface of the gastrointestinal lumen. The objectives of the present study were to evaluate the clinical features, possible risk factors, endoscopic features, and histopathological patterns of gastrointestinal polyps among adult Sudanese patients. Methods: This was a retrospective, descriptive, cross-sectional hospital-based study conducted at the Soba University Hospital Department of Endoscopy from March 2017 to March 2020. This study was conducted on patients with gastrointestinal polyps found upon colonoscopy or flexible sigmoidoscopy. Results: The incidence of colonic polyps was 11.7% (237/2019). The mean age was 51 ± 18 years, and the male-to-female ratio was 1.5:1. The indications for colonoscopy were bleeding per rectum (28.7%; n=68), chronic constipation (16.5%; n=39), a change in bowel habits (11%; n=26), anaemia (8.8%; n=20), melena (3.8%; n=9), diarrhoea (3.8%; n=9%) and surveillance (20%; n=48%). A family history of cancer was directly correlated with the size of the colon polyp on endoscopy and the grade of dysplasia on histopathology (p values=0.01 and 0.02, respectively). The use of NSAIDs was significantly correlated with the site of colonic polyps, while no significant correlation was found with smoking status, alcohol consumption, or family history of polyps (p value=0.02). The main site of polyps for colonic polyps was the left colon (67.4%). Histopathology reports were available for 65.4% (n=155) of patients with polyps. The predominant histopathological type in the lower gastrointestinal tract was adenomatous in 46.4% (n=72) of patients. Conclusion: The frequency of colonic polyps was 11.7%. The main presentation for colonic polyps was bleeding per rectum. A small size < 0.5 cm and a sessile shape were the dominant endoscopic features of the lower gastrointestinal polyps. However, adenomatous polyps were the most common histopathological type of polyp among ......

Association of podoplanin expression to histopathological grades of oral epithelial dysplasia and oral squamous cell carcinoma.

To determine the expression of podoplanin, and to correlate it with histopathological grades in oral epithelial dysplasia and oral squamous cell carcinoma cases. The retrospective, analytical, cross-sectional study was conducted at the City Laboratory, Peshawar, Pakistan, and comprised specimen block data of histologically diagnosed cases of oral benign lesions, dysplastic lesions and oral squamous cell carcinoma from January 2017 to August 2021. Two sections (4um) were cut from each specimen block for Haematoxylin and Eosin staining and immunohistochemistry. The slides were re-evaluated by two pathologists for confirmation of the diagnosis, and podoplanin marker was applied to cases selected using immunohistochemistry. Data was analysed using SPSS 22. Of the 80 cases identified, 68(85%) were analysed. There were 20(29.4%) benign cases; 11(55%) females and 9(45%) males with mean age 39.90±16.23 years, 20(29.4%) oral dysplastic cases; 14(70%) males and 6(30%) females with mean age 57.75±12.02 years, and 28(41.2%) oral squamous cell carcinoma cases; 17(61%) males and 11(39%) females with mean age 50.55±14.80 years. Podoplanin expression in oral epithelial dysplasia cases was significant (p=0.028), while it was not significant in the other 2 groups (p>0.05). Podoplanin when used along with histopathological evaluation could aid as an adjuvant technique in the diagnosis and grading of oral epithelial dysplasia.

Molecular characterization of the evolution of premalignant lesions in the upper aerodigestive tract.

Early relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is a heterogeneous disease which may develop in large premalignant fields of genetically altered cells. Yet knowing which individuals will progress and develop clinically significant cancers during their lifetimes remains one of the most important challenges of reducing HNSCC morbidity and mortality. To further elucidate the molecular mechanisms, we performed a focused analysis of the genome and immune microenvironment from multiple, matched normal squamous tissue, premalignant lesions, as well as primary and recurrent tumors from seven patients with p16-negative HNSCC. We performed targeted panel Next Generation Sequencing (161 genes) to analyze somatic variants from sequentially collected, matched formalin-fixed paraffin-embedded tissue (normal, premalignant, HNSCC) from two patients. These samples plus samples from five additional patients were analyzed with the Nanostring PanCancer Immune Panel. In addition, we performed shallow whole genome sequencing (0.5x coverage on average) on samples from three of these patients. Patients were, apart from one case, primarily treated with curative-intent surgery, and received subsequent adjuvant treatment, if indicated. The most frequently mutated genes were TP53 and NOTCH1. Other mutated genes included NOTCH3 and CDKN2A, among others. A significant number of mutations were private to dysplasia and invasive carcinoma, respectively, however, almost 20% were shared between them. Increasing genomic instability was observed when comparing histologically normal squamous mucosa with higher levels of dysplasia. High-grade dysplasia showed similarly rearranged genomes as invasive carcinoma. Pathways related to interferon alpha and gamma response were upregulated even in moderate dysplastic lesions with increasing expression in higher grades of dysplasia and carcinoma. SPINK5, a known tumor suppressor gene in HNSCC, was already downregulated in low-grade dysplastic lesions, indicating an early deactivation in the evolution of the disease. Genomic alterations as well as aberrant immune gene expression can be observed early in the evolution of tumors of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.

Human fecal alpha-glucosidase activity and its relationship with gut microbiota profiles and early stages of intestinal mucosa damage

ObjectivesWe investigated potential relationships among initial lesions of the intestinal mucosa, fecal enzymatic activities and microbiota profiles. MethodsFecal samples from 54 volunteers were collected after recruitment among individuals participating in a colorectal cancer (CRC) screening program in our region (Northern Spain) or attending for consultation due to clinical symptoms; intestinal mucosa samples were resected during colonoscopy. Enzymatic activities were determined in fecal supernatants by a semi-quantitative method. The fecal microbiota composition was determined by 16S rRNA gene-based sequencing. The results were compared between samples from clinical diagnosis groups (controls and polyps), according with the type of polyp (hyperplastic polyps or conventional adenomas) and considering the grade of dysplasia for conventional adenomas (low and high grade dysplasia). ResultsHigh levels of α-glucosidase activity were more frequent among samples from individuals diagnosed with intestinal polyps, reaching statistical significance for conventional adenomas and for low grade dysplasia adenomas when compared to controls. Regarding the microbiota profiles, higher abundance of Christensenellaceae_R-7 group and Oscillospiraceae_UCG-002 were found in fecal samples displaying low α-glucosidase activity as compared with those with higher activity as well as in controls with respect to conventional adenomas. A relationship was evidenced among intestinal mucosal lesions, gut glucosidase activities and intestinal microbiota profiles. ConclusionsOur findings suggest a relationship among altered fecal α-glucosidase levels, the presence of intestinal mucosal lesions, which can be precursors of CRC, and shifts in defined microbial groups of the fecal microbiota.

Oral epithelial dysplasia detection and grading in oral leukoplakia using deep learning

BackgroundThe grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia.MethodsFour convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model.ResultsEfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4–90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4–90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843).ConclusionsE-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice.

Leukoplakia with Diverse Grades of Epithelial Dysplasia – A Case Series and Review of Literature with Updated Management Protocol

Oral leukoplakia is considered the most potentially malignant disorder of the oral cavity, with a high risk of malignant transformation. Based on the clinical manifestation, it has been classified as a homogeneous and non-homogeneous variant. It has been considered predominantly a white lesion of the oral cavity that cannot be classified under any other definable lesions. Leukoplakia is a term used to describe the lesion clinically. There are various components responsible for the threatening change of oral leukoplakia. The clinical diagnosis of leukoplakia is confirmed by histopathology, which commonly indicates intense epithelial dysplasia. This manuscript describes a series of cases diagnosed clinically as leukoplakia and their grades of epithelial dysplasia, a Review of literature about etiology and the key pathogenesis behind it, risk determinants for malignant transformation, chair side investigation for epithelial dysplasia, and updated management protocol.

Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?

Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions. We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded. Sixty-six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high-grade dysplastic nevi, and 50% (n: 33) were low-grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high-grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17-12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15-13.2), and total colour count (OR = 3.21, 95% CI, 1.2-8.5) were significant predictive factors for the lesions with high-grade dysplasia and melanomas. To avoid the underdiagnosis of both melanomas and high-grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1-year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high-grade dysplasia.

A Quantitative Assessment of Apoptotic Index with Varying Histological Degree of Dysplasia and Squamous Cell Carcinoma of Oral Cavity - A Light Microscopic Study.

The aim of the present study was to quantitatively assess the apoptotic index at a light microscopic level in hyperkeratosis with varying histological degrees of dysplasia and different grades of oral squamous cell carcinoma (OSCC) and its correlation with prognostic significance. The study included the histo-pathologically diagnosed cases of hyperkeratosis with varying degrees of dysplasia and different grades of OSCC, which were retrieved from the archives of the department, and clinical details were retrieved from the case records of the patients. The sample size consisted of 80 biopsied cases, divided into seven groups of 10 experimental cases and one group of 10 cases of normal mucosa as a control group. The age range of 50-59 shows maximum patients of hyperkeratosis with varying degrees of dysplasia and OSCC. Maximum apoptotic bodies were seen in cases of severe dysplasia and well-differentiated cases of OSCC. There was an observational difference noticed in apoptotic bodies between the patients who had less than 1-year disease-free survival rate. The apoptotic cells are being seen using routine light microscopy techniques with hematoxylin and eosin staining. In different grades of squamous cell carcinoma, a decrease in the apoptotic count was noticed from well-differentiated squamous cell carcinoma toward poorly differentiated squamous cell carcinoma cases. Increased mean apoptotic bodies were observed in patients showing less than 1 year of survival.

Recurrence and malignant transformation of laryngeal leukoplakia treated with CO2 laser: A systematic review and meta-analysis.

Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein

ObjectiveTo investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. MethodsWe selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. ResultsIn gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). ConclusionThe detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review.

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation.

New insights into the role of the oral leukoplakia microenvironment in malignant transformation.

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

Oral leukoplakia: an update for dental practitioners

Statement of the problem Oral leukoplakia (OLK) is a common mucosal pathology frequently encountered in general dental practice which belongs to a group of conditions known as oral potentially malignant disorders (OPMDs). This inferred risk of progression to oral squamous cell carcinoma warrants an understanding of the etiology of this condition, its clinical presentation, and how patients diagnosed with OLK are managed in both general and specialist care practices. Purpose of the review To update the dental practitioner on the current understanding concerning the diagnosis and management of OLK. Methods A search strategy was conducted in the MEDLINE Ovid and Embasse databases and the Cochrane Library. No time limit was applied. The search results were limited to those in the English language. Discussion The etiology for oral white patches can range considerably from innocuous frictional keratosis to oral squamous cell carcinoma. A thorough history and clinical examination should precede referrals to secondary care, with the elimination of risk factors a priority. In cases where white patches are suspicious or remain despite managing known risk factors, prompt referral to a specialist centre is warranted. Despite the extent of research in this field, controversy remains in OLK management and there is currently no agreed international consensus on the management of OLK from governing bodies. Therefore, management is primarily governed by local contemporaneous guidelines, and management is based on the most reliable predictor of malignant transformation: the grade of dysplasia. Despite various treatments, OLK may still undergo transformation to malignancy. Conclusions General dental practitioners (GDPs) are the health care practitioners best placed to detect OLK on a daily basis, given the volume of patients encountered from various backgrounds. An understanding of the causes and presentation of OLK will allow GDPs to recognise this entity in practice, and facilitate further management and treatment in a bid to prevent transformation.

Detection of (pre)cancerous colorectal lesions in Lynch syndrome patients by microsatellite instability liquid biopsy

Lynch syndrome (LS) is an inherited condition characterized by an increased risk of developing cancer, in particular colorectal cancer (CRC). Microsatellite instability (MSI) is the main feature of (pre)cancerous lesions occurring in LS patients. Close endoscopic surveillance is the only option available to reduce CRC morbidity and mortality. However, it may fail to intercept interval cancers and patients’ compliance to such an invasive procedure may decrease over the years. The development of a minimally invasive test able to detect (pre)cancerous colorectal lesions, could thus help tailor surveillance programs in LS patients. Taking advantage of an endoscopic surveillance program, we retrospectively assessed the instability of five microsatellites (BAT26, BAT25, NR24, NR21, and Mono27) in liquid biopsies collected at baseline and possibly at two further endoscopic rounds. For this purpose, we tested a new multiplex drop-off digital polymerase chain reaction (dPCR) assay, reaching mutant allele frequencies (MAFs) as low as 0.01%. Overall, 78 plasma samples at the three time-points from 18 patients with baseline (pre)cancerous lesions and 18 controls were available for molecular analysis. At baseline, the MAFs of BAT26, BAT25 and NR24 were significantly higher in samples of patients with lesions but did not differ with respect to the grade of dysplasia or any other clinico-pathological characteristics. When all markers were combined to determine MSI in blood, this test was able to discriminate lesion-bearing patients with an AUC of 0.80 (95%CI: 0.66; 0.94).

Supratrochlear Rim Is Correlated With Isolated Patellar Chondromalacia on Magnetic Resonance Imaging of the Knee

To investigate the relationship between the supratrochlear rim and isolated patellar chondromalacia (PC) using magnetic resonance imaging (MRI) scans of the knee. Patients without patellofemoral pain (control group) and patients with patellofemoral pain and diagnosed with stage III or IV PC based on MRI (defect group) were retrospectively identified. Patients with a history of patellar subluxation were excluded. We used patient MRI scans to perform 20 anatomical measurements of the patellofemoral joint. We also performed 2 measurements of the anterior femoral curvature. A total of 30 patients (29 ± 8.7 years) were in the control group, and 20 patients were in the defect group (29.4 ± 9.7 years). The maximum curvature (P < .001) and mean curvature (P < .001) of the anterior femoral condyle were found statistically significantly different between the groups. Patellotrochlear index (P= .03) and Insall-Salvati index (P < .001) were also found statistically significantly different between the 2 groups. Patella type III and trochlear dysplasia grade B were found more common in the defect group. In this Level III prognostic, case-control study, we have shown through MRI knee measurements that the isolated patellar chondromalacia in patients without a history of patellar subluxation and dislocation is correlated with the increased anterior femoral curvature in combination with patella alta.

P217 Rate of undetected dysplasia at colectomy in patients with IBD - What are we missing?

Abstract Background Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia. Methods We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both. Results Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis. In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both. In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well. Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy. Further results are shown in Table 1. Conclusion The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.