Dysplastic Lesions Research Articles

PARP1-targeted fluorescence molecular endoscopy as novel tool for early detection of esophageal dysplasia and adenocarcinoma

BackgroundEsophageal cancer is one of the 10 most common cancers worldwide and its incidence is dramatically increasing. Despite some improvements, the current surveillance protocol with white light endoscopy and random untargeted biopsies collection (Seattle protocol) fails to diagnose dysplastic and cancerous lesions in up to 50% of patients. Therefore, new endoscopic imaging technologies in combination with tumor-specific molecular probes are needed to improve early detection. Herein, we investigated the use of the fluorescent Poly (ADP-ribose) Polymerase 1 (PARP1)-inhibitor PARPi-FL for early detection of dysplastic lesions in patient-derived organoids and transgenic mouse models, which closely mimic the transformation from non-malignant Barrett’s Esophagus (BE) to invasive esophageal adenocarcinoma (EAC).MethodsWe determined PARP1 expression via immunohistochemistry (IHC) in human biospecimens and mouse tissues. We also assessed PARPi-FL uptake in patient- and mouse-derived organoids. Following intravenous injection of 75 nmol PARPi-FL/mouse in L2-IL1B (n = 4) and L2-IL1B/IL8Tg mice (n = 12), we conducted fluorescence molecular endoscopy (FME) and/or imaged whole excised stomachs to assess PARPi-FL accumulation in dysplastic lesions. L2-IL1B/IL8Tg mice (n = 3) and wild-type (WT) mice (n = 2) without PARPi-FL injection served as controls. The imaging results were validated by confocal microscopy and IHC of excised tissues.ResultsIHC on patient and murine tissue revealed similar patterns of increasing PARP1 expression in presence of dysplasia and cancer. In human and murine organoids, PARPi-FL localized to PARP1-expressing epithelial cell nuclei after 10 min of incubation. Injection of PARPi-FL in transgenic mouse models of BE resulted in the successful detection of lesions via FME, with a mean target-to-background ratio > 2 independently from the disease stage. The localization of PARPi-FL in the lesions was confirmed by imaging of the excised stomachs and confocal microscopy. Without PARPi-FL injection, identification of lesions via FME in transgenic mice was not possible.ConclusionPARPi-FL imaging is a promising approach for clinically needed improved detection of dysplastic and malignant EAC lesions in patients with BE. Since PARPi-FL is currently evaluated in a phase 2 clinical trial for oral cancer detection after topical application, clinical translation for early detection of dysplasia and EAC in BE patients via FME screening appears feasible.

A European Multicentric Investigation of Atypical Melanocytic Skin Lesions of Palms and Soles: The iDScore-PalmoPlantar Database.

Background: The differential diagnosis of atypical melanocytic palmoplantar skin lesions (aMPLs) represents a diagnostic challenge, including atypical nevi (AN) and early melanomas (MMs) that display overlapping clinical and dermoscopic features. We aimed to set up a multicentric dataset of aMPL dermoscopic cases paired with multiple anamnestic risk factors and demographic and morphologic data. Methods: Each aMPL case was paired with a dermoscopic and clinical picture and a series of lesion-related data (maximum diameter value; location on the palm/sole in 17 areas; histologic diagnosis; and patient-related data (age, sex, family history of melanoma/sunburns, phototype, pheomelanin, eye/hair color, multiple/dysplastic body nevi, and traumatism on palms/soles). Results: A total of 542 aMPL cases-113 MM and 429 AN-were collected from 195 males and 347 females. No sex prevalence was found for melanomas, while women were found to have relatively more nevi. Melanomas were prevalent on the heel, plantar arch, and fingers in patients aged 65.3 on average, with an average diameter of 17 mm. Atypical nevi were prevalent on the plantar arch and palmar area of patients aged 41.33 on average, with an average diameter of 7 mm. Conclusions: Keeping in mind the risk profile of an aMPL patient can help obtain a timely differentiation between malignant/benign cases, thus avoiding delayed and inappropriate excision, respectively, with the latter often causing discomfort/dysfunctional scarring, especially at acral sites.

Cholangioscopy-assisted endoscopic mucosal resection for a mildly dysplastic lesion of the common bile duct: a pilot exploration for super minimally invasive surgery.

Cholangioscopy-assisted endoscopic mucosal resection for a mildly dysplastic lesion of the common bile duct: a pilot exploration for super minimally invasive surgery.

A145 UNDERWATER EMR FOR LARGE FLAT DYSPLASTIC COLORECTAL LESIONS IN PATIENTS WITH CHRONIC ULCERATIVE COLITIS

Abstract Background Patients with chronic ulcerative colitis are at increased risk of colorectal cancer, in part due to increased prevalence of dysplastic lesions. To reduce CRC risk, endoscopic resection is preferable to surgery if feasible. However, large flat lesions can be challenging to remove endoscopically. We report our experience with underwater EMR for large, flat ulcerative colitis-associated dysplastic lesions. Aims To evaluate the safety and efficacy of UEMR for treatment of flat/sessile colorectal lesions with dysplasia, without overt signs of invasive cancer. To analyze rates of complications and outcomes for patients undergoing UEMR and compare to alternative methods of treatment for similar lesions. Methods We reviewed our IBD patient database from 2021 to 2023 for ulcerative colitis patients referred for large (≥ 20 mm diameter) flat/sessile colorectal lesions without overt signs of invasive cancer, who subsequently underwent underwater EMR. The procedure was performed by an endoscopist with extensive experience in UEMR for large colorectal lesions. Results Eleven de novo lesions in 8 patients (4 female; age 58 ± 14) were successfully treated with single-session UEMR. Mean lesion size was 42 ± 22 mm (range 20 to 80 mm); all morphologically flat (Paris IIa or IIb). Three cases were resected en bloc; the remainder piecemeal. Pathology showed tubulovillous adenoma, N=4 (36%); tubular adenoma, N=5 (45%); traditional serrated adenoma, N=1 (9%); sessile serrated lesion, N=1, (9%); high-grade dysplasia, N=1 (9%). There were no cases of invasive cancer. Endoscopic follow-up available for 5 patients over 10.4 ± 2 months showed benign diminutive recurrent/residual lesions in 2 cases, both amenable to UEMR. There were no procedural complications. Conclusions In this series of large, flat dysplastic CUC-associated lesions, UEMR was safe and effective, obviating surgery and endoscopic submucosal dissection. Funding Agencies None

High-definition chromoendoscopy results in more significant dysplasia detection than white light endoscopy with random biopsies in ulcerative colitis patients: A single-center retrospective study.

The goal of this study was to determine whether high-definition white light endoscopy with random biopsies (HD-WLR) or chromoendoscopy (HDCE) yielded a higher dysplasia detection rate in ulcerative colitis patients. Ulcerative colitis (UC) patients have a 2.4-fold increased future risk of developing colorectal cancer compared to the general population and require careful dysplasia screening modalities. Both HD-WLR and HDCE are regularly used, and recent guidelines do not suggest a preference. UC patients who underwent dysplasia surveillance at our site between January 2019 and 2021 were retrospectively reviewed. We calculated the dysplasia detection rate of both techniques at the first CRC screening colonoscopy. Eighteen dysplastic lesions were detected in total, 3 by HD-WLR and fifteen by HDCE. Dysplasia was detected in 4% (3/75) and 20% (15/75) of UC patients by HD-WLR and HDCE respectively, with significantly fewer biopsies (4.44 ± 4.3 vs 29.1 ± 13.0) required using the former. HD-WLR detected 2 polypoid and one non-polypoid lesion, while HDCE detected eleven polypoid and 4 non-polypoid lesions. No invisible dysplasia or colorectal cancer was detected. Screening was performed at 10.8 ± 4.8 and 9.72 ± 3.05 years following UC diagnosis for HDCE and HD-WLR respectively. Median withdrawal time was 9.0 ± 2.7 minutes (HD-WLR) vs 9.6 + 3.9 minutes (HDCE). HDCE is associated with higher dysplasia detection rates compared to HD-WLR in a UC patient population. Given the former technique is less tedious and costly, our findings complement existing studies that suggest HDCE may be considered over HD-WLR for UC dysplasia surveillance.

Abstract B008: The polyclonal path towards malignant transformation in familial adenomatous polyposis

Abstract The widely accepted paradigm that cancer initiation is a monoclonal event has not been definitively resolved. This is largely due to the limitations of experimental systems to study cancer initiation, a definitively transient step in tumorigenesis. Individuals with familial adenomatous polyposis (FAP) possess a germline APC mutation, leading to hundreds of colonic polyps in adolescence and an eventual 100% lifetime risk of colorectal cancer. As such, total colectomies are performed once polyp burden becomes unmanageable and provide the resected colons from FAP donors provide a source of histologically normal mucosa, benign and dysplastic polyps, and, on rare occasions, adenocarcinomas, and serve as an exemplary model disease to understand human tumorigenesis. Through whole genome sequencing of 123 independent samples from six patients, we reveal the polyclonal origins of tumorigenesis in FAP. We characterize and contrast the genomic landscape and relative timing of driver mutation acquisition across normal to dysplastic and invasive colon tissue and compare this with multi-region sequencing data from sporadic colorectal cancers (CRC). We find that only early sporadic CRC drivers are common across the more heterogeneous premalignant stages. Selection, as assessed based on the ratio of nonsynonymous to synonymous mutations (dN/dS), is higher in benign than dysplastic FAP lesions and in sporadic adenomas relative to carcinomas. Phylogenetic reconstruction and pairwise sample comparisons reveal extensive heterogeneity and subclonal sharing within a patient’s benign and dysplastic lesions. Using a mechanistic mathematical model, we infer polyclonality for 90-100% of benign and 53-83% of dysplastic samples. Based on these findings, we propose a conceptual framework for the polyclonal origin of intestinal malignancies where inconsequential mutations, arising during colon formation in utero, are present across the colon and are valuable markers to uncover polyclonal ancestry. Citation Format: Ryan O. Schenck, Aziz Khan, Aaron M. Horning, Edward D. Esplin, HTAN Consortia, William J. Greenleaf, James M. Ford, Michael P. Snyder, Christina Curtis. The polyclonal path towards malignant transformation in familial adenomatous polyposis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B008.

Distinct senescence mechanisms restrain progression of dysplastic nevi.

Telomerase reverse transcriptase (TERT) promoter mutations (TPMs) are frequently found in different cancer types, including ∼70% of sun-exposed skin melanomas. In melanoma, TPMs are among the earliest mutations and can be present during the transition from nevus to melanoma. However, the specific factors that contribute to the selection of TPMs in certain nevi subsets are not well understood. To investigate this, we analyzed a group of dysplastic nevi (DN) by sequencing genes commonly mutated in melanocytic neoplasms. We examined the relationship between the identified mutations, patient age, telomere length, histological features, and the expression of p16. Our findings reveal that TPMs are more prevalent in DN from older patients and are associated with shorter telomeres. Importantly, these TPMs were not found in nevi with BRAF V600E mutations. Conversely, DN with BRAF V600E mutations were observed in younger patients, had longer telomeres and a higher proportion of p16-positive cells. This suggests that these nevi arrest growth independently of telomere shortening through a mechanism known as oncogene-induced senescence (OIS). These characteristics extend to melanoma-sequencing datasets, where melanomas with BRAF V600E mutations were more likely to have a CDKN2A inactivation, overriding OIS. In contrast, melanomas without BRAF V600E mutations showed a higher frequency of TPMs. Our data imply that TPMs are selected to bypass replicative senescence (RS) in cells that were not arrested by OIS. Overall, our results indicate that a subset of melanocytic neoplasms face constraints from RS, while others encounter OIS and RS. The order in which these barriers are overcome during progression to melanoma depends on the mutational context.

Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

Evaluation of the Factors Associated with Post-Operative Outcome in Patients of Ulcerative Colitis Undergoing Ileal Pouchanal Anastomosis with Comparison of Functional Outcome between Stapler and Hand-Sewn Anastomosis

ntroduction Ulcerative colitis defined as a non-granulomatous idiopathic inflammatory disease which mainly affects the colon and rectum. The disease may arise at any age but most commonly affects the adults between the age group of 30–40 years.1,2. The etiology of the disease is multifactorial, involving genetic predisposition, dysregulated immune responses, epithelial barrier defects and environmental factors. No sex predilection is seen in ulcerative colitis.3,5 The peak age of onset of disease is between 30 to 40 years.4,6 The environmental factors has also been found to play an important role in the etiopathogenesis of ulcerative colitis. Cigarette smoking is one of the major factor associated with ulcerative colitis, non-smokers have a milder disease course and active smokers are less likely to develop ulcerative colitis7 Appendectomy also confers a protective effect against ulcerative colitis, especially in young patients operated for acute appendicitis.8. Classic findings in endoscopy in patients with ulcerative colitis include loss of normal vascular pattern, erythema, erosions, granularity, friability, ulcerations and bleeding9 . The primary aim of medical management is to induce and maintain remission with the long-term goals of improving quality of life and prevent disability. Absolute indications for surgery include uncontrolled hemorrhage, perforation, and colorectal carcinoma or dysplastic lesions not amenable to endoscopic removal.10 Surgery is also indicated in refractory acute severe ulcerative colitis or medically refractory disease. The most commonly performed surgery for ulcerative colitis is restorative proctocolectomy with ileal pouchanal anastomosis (IPAA). An important aspect of the surgery is the use of either sutures or staplers for anastomosis. Two types of ileal pouch-anal anastomosis (IPAA) have been described: a mucosectomy of the rectal stump followed by a hand-sewn ileal pouch-anal anastomosis.11 The alternative technique is to retain the mucosa of the rectal stump and perform a stapled pouch-anal anastomosis.

Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi.

The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma. In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN. A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination. Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%). This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.

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.

P525 Utilisation of endoscopic ultrasonography for submucosal cushion measurement to determine eligibility for endoscopic submucosal dissection in ulcerative colitis-associated dysplasia: A case series

Abstract Background Endoscopic submucosal dissection (ESD) has gained traction as an effective therapy for ulcerative colitis (UC)-associated dysplasia, yet identifying fitting ESD candidates is challenging by substantial submucosal (SM) fibrosis from chronic inflammation. We report our experience utilising endoscopic ultrasonography (EUS) to assess ESD eligibility by measuring SM cushion thickness. Methods Retrospective case-series includes nine patients who were diagnosed or referred to as UC-associated dysplasia in surveillance colonoscopies between August 2017 and October 2023. After scanning dysplastic lesions (Fig A-B), hyaluronic acid solution was injected into the SM layer (Fig C). EUS with a mini-probe quantified SM cushion beneath the dysplastic lesion (Fig D), and ESD was performed in cases with at least 2.0 mm of SM cushion thickness (Fig E-F). Results Among ten cases from nine patients, eight cases met the criteria and underwent ESD, while two cases (Patient 3, Patient 7) were regarded as unsuitable for ESD with SM cushion thickness less than 2.0 mm. Median disease duration was 19 years, and median age at diagnosis of UC-associated dysplasia was 50 years. Median SM cushion thickness ranged from 4.2 to 6.9 mm. Median procedure time was 50 minutes, and median size of resected specimens and lesions were 31.5 x 24.5 mm and 16.0 x 12.5 mm, respectively. en bloc resection was achieved in all cases, with an 87.5% R0 resection rate. No perforation occurred; only one required post-discharge endoscopic bleeding control after four days post-discharge. Conclusion EUS-measured SM cushion thickness may be a valid approach that provides an objective criterion for determining ESD eligibility in UC-associated dysplasia. This would help guide individualised treatment in UC-associated dysplasia, reducing unnecessary procedures or surgery.

Hyperplastic, dysplastic and neoplastic lesions associated with a model of carcinogenesis induced by DMBA in the salivary glands of BALB-c mice

The aim of this work was to develop a mouse model of submandibular salivary gland carcinogenesis by chemical induction and to perform a revision of the literature on similar models using the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA). The descriptive review was carried out on published works in English and Spanish languages, from the period 1977-2023, which included different animal models of chemical carcinogenesis induced by DMBA in salivary glands. Articles were reviewed in order to analyze the effectiveness of the carcinogenesis induction. For our model, BALB/c mice were used. Animals were anesthetized and after surgery to expose the submandibular gland, each mouse was injected with solution of DMBA 2% in corn oil. Mice were monitored weekly until sacrifice at week 12. The samples were processed with the routine histological methods. The results from the descriptive review showed that DMBA is mainly administered by Intraglandular injections into the submandibular glands after surgical exposure, being both pellets and solutions used for the induction, and rats more common than mice. This revision summarizes the research results of previous studies and demonstrates which model has greater reproducibility. Our results showed that one single injection of DMBA directly into the surgically exposed submandibular gland was an optimal technique to induce the tumor at the desired site. Edema was observed in the surgical area during the first 2 weeks. From week 5, the mice presented internal hardness and hair loss in the glandular area; 50% of the animals presented palpable and measurable tumor masses from week 10. Microscopic observations showed that 89% of the mice developed malignant neoplasms: Carcinomas in situ, micro-invasive and invasive (6/8); sarcomas (1/8), and carcinosarcoma (1/8). Associated lesions were atypical ductal hyperplasia; periductal fibrosis, and sarcomatous stroma. This model marks a difference with the subcutaneous injection technique, without surgery, which does not allow the carcinogen to be adequately directed to the gland.

Diagnostic Challenges during Inflammation and Cancer: Current Biomarkers and Future Perspectives in Navigating through the Minefield of Reactive versus Dysplastic and Cancerous Lesions in the Digestive System.

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.

Lesion detection and classification in dermoscopic images using optimal threshold based on Newton Raphson iterative method

Automatic image thresholding is commonly used in the area of computer vision and pattern recognition for object detection. This research work proposes a new method of lesion detection in dermoscopic images using an optimal threshold based on the Newton-Raphson iteration algorithm for diagnosing melanoma. The proposed method incorporates a new strategy of finding the optimal threshold using first-order and second-order edge derivatives. The first- and second-order derivatives values obtained from the images are applied in the Newton-Raphson method which, in turn, converges to a value after a number of iterations. The converged value is considered the optimal threshold and used as a parameter for the separation of lesion regions from healthy skin in dermoscopic images. To test the proposed system performance, the experiment is carried out on two standard data sets, the ISIC Archive and the PH2, of dermoscopic images using different classifiers such as the Naive Bayes (NB), AdaBoost and Bag of Visual words (BOVW). The proposed segmentation technique segments the lesion regions from skin images and Bag of visual words classifier classifies the dermoscopic images into different classes namely common nevi, atypical nevi and melanoma. The proposed thresholding-based segmentation performance is compared against the Otsu method and Otsu using genetic algorithm. The experimental findings reveal that the proposed Newton-Raphson iterative method surpasses various state-of-the-art and recent methods in relation to computational speed, error rate, sensitivity, and accuracy.

Optical coherence tomography: Promising imaging technique for the diagnosis of oral mucosal diseases.

This review aims to summarize the latest application of optical coherence tomography (OCT) in oral mucosal diseases, promoting an accurate and earlier diagnosis of such disorders, which are difficult to be differentiated. References on the application of OCT in oral mucosal diseases were mainly obtained from PubMed, Embase, Web of Science and Scopus databases, using the keywords: "optical coherence tomography and 'oral mucosa/oral cancers/oral potentially malignant diseases/oral lichen planus/oral leukoplakia/oral erythroplakia/discoid lupus erythematosus/oral autoimmune bullous diseases/oral ulcers/erythema multiforme/oral mucositis'". It is found that OCT is showing a promising application potential in the early detection, diagnosis, differential diagnosis, monitoring of oral cancer and oral dysplastic lesions, as well as the delineation of tumor margins. OCT is also playing an increasingly important role in the diagnosis of oral potentially malignant disorders, oral mucosal bullous diseases, oral ulcerative diseases, erythema multiforme, and the early detection of oral mucositis. Optical coherence tomography, as a novel optical technique featured by real-time, noninvasive, dynamic and high-resolution imaging, is of great use to serve as an adjunct tool for the diagnosis, differential diagnosis, monitoring and therapy evaluation of oral mucosal diseases.

Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients

BackgroundTopical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited.MethodsFifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year.ResultsThe overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013–0.915).ConclusionTopical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

Evaluation of MMP-9, MMP-13, MMP-21, and TIMP-1 expressions in malign melanom, dysplastic nevi, and banal nevi.

Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study aims to search the expression differences of MMP-9, MMP-13, MMP-21, and TIMP-1 between malignant melanoma (MM), intradermal nevi (IDN), and dysplastic nevi (DN). MMP-9, MMP-13, MMP-21, and TIMP-1 antibodies were studied immunohistochemically for 60 cases in our pathology clinic archive between 2013 and 2014. The MM group had the highest expression percentage and intensity for MMP-9 (p<0.001). There was no statistical significance between MMP-13 expression intensities of lesion cells and stromal cells and stromal expression intensities (p>0.05). MMP-21 lesion staining intensities in DN and MM compared to IDN were statistically significant (p=0.001, p=0.011, respectively). For TIMP-1, there was a significant difference between the IDN and the MM group regarding the staining proportion of lesion cells (p<0.01). There was a statistically significant difference in all groups according to lesion cells' expression intensity. (IDN-DN p<0.001, IDN-MM p=0.044, DN-MM p<0.001). The following markers can be helpful when lesions cannot be differentiated; increased staining proportions and intensity of MMP-9 in both lesion and stromal cells favor MM in cases where MM and IDN cannot be differentiated. The increased MMP-13 staining proportion of lesion cells can favor DN in cases where the pathologist cannot differentiate DN and MM. Intense expression of MMP-21 by lesion cells can be a potential marker for evaluating the lesion in favor of DN in cases where DN and IDN cannot be differentiated. The high expression intensity of TIMP-1 in lesion cells can favor DN in cases where there is ambiguity between DN and MM. High expression proportion and intensity of stromal cells of TIMP-1 can be useable in favor of MM in cases where MM and DN cannot be differentiated.

Recurrent ocular surface squamous neoplasia treated with orbital exenteration

Ocular surface squamous neoplasia (OSSN) consists of an array of dysplastic, pre-invasive and malignant squamous lesions that impair the ocular surface. We report a case of a 61-year-old female with recurrent OSSN and had chronic hepatitis B. She was managed surgically, excision of the lesion and cryotherapy with amniotic membrane grafting with topical Mitomycin C 0.02% was performed. She came back with recurrence after 8 months and was managed with 6 cycles of Mitomycin C. After 9 months she reported back with recurrence with light perception vision and underwent orbital exenteration.

Diethylnitrosamine-Induced Liver Tumorigenesis in Mice Under High-Hat High-Sucrose Diet: Stepwise High-Resolution Ultrasound Imaging and Histopathological Correlations.

The hepatotoxic N-nitroso compound diethylnitrosamine (DEN) administered intraperitoneally (i.p.) induces liver neoplasms in rodents that reproducibly recapitulate some aspects of human hepatocarcinogenesis. In particular, DEN drives the stepwise formation of pre-neoplastic and neoplastic (benign or malignant) hepatocellular lesions reminiscent of the initiation-promotion-progression sequence typical of chemical carcinogenesis. In humans, the development of hepatocellular carcinoma (HCC) is also a multi-step process triggered by continuous hepatocellular injury, chronic inflammation, and compensatory hyperplasia that fuel the emergence of dysplastic liver lesions followed by the formation of early HCC. The DEN-induced liver tumorigenesis model represents a versatile preclinical tool that enables the study of many tumor development modifiers (genetic background, gene knockout or overexpression, diets, pollutants, or drugs) with a thorough follow-up of the multistage process on live animals by means of high-resolution imaging. Here, we provide a comprehensive protocol for the induction of hepatocellular neoplasms in wild-type C57BL/6J male mice following i.p. DEN injection (25mg/kg) at 14days of age and 36weeks feeding of a high-fat high-sucrose (HFHS) diet. We emphasize the use of ultrasound liver imaging to follow tumor development and provide histopathological correlations. We also discuss the extrinsic and intrinsic factors known to modify the course of liver tumorigenesis in this model.