Mucosal Lesions Related to Toombak Dipping in the Sudanese

Background: Mucosal changes related to smokeless tobacco dipping appear to be influenced by many factors; including duration of dipping, frequency of dipping, chemical ingredients of the dipped stuff, in addition to possible genetic and racial factors. In the Sudan the habit of using smokeless tobacco (Toombak) is very common, and it is associated with pathological mucosal changes classified into five distinct clinical presentations: Presentation I; wrinkling with slight discoloration, Presentation II; Café au lait discoloration (Brownish discoloration), Presentation III; smoke-white discoloration, Presentation IV; grizzle discoloration, and Presentation V; cotton-white discoloration. Material and Methods: In this observational prospective study, a survey of oral cancer across 16 different localities was held in the Sudan. A total of 285 Toombak dippers agreed to be examined and of them 161 patients were found to have Toombak dipper-lesions. The clinical presentations of these lesions were identified and recorded into 5 different presentation categories. Furthermore, 64 specimens were cut and stained with Haematoxylin and Eosin (H&E). Microscopic diagnosis was obtained using both WHO-5-Point grading classification and the binary system. The history of the time span was matched with the related clinical and microscopic findings. Results: Regarding the 161 cases; the lower vestibule was the preferred dipping site in 75(46.6%) cases. The average Age of Commencement (AoC) was 24.5 years. The average Estimated Contact Hours (ECH) was 22,338 ± 40,824 hours; equal to 2.55 contact years in lifetime. The dominant mucosal clinical presentation was wrinkling with/without slight discolouration; found in 54 cases, and accounting for 33.6% of the sample. Of the 64 specimens, 51 cases showed hyperkeratosis, 11 cases showed mild dysplasia and the remaining three cases showed severe dysplasia; two cases were cotton- white presentations, and one case was a grizzle presentation. Conclusion: Twenty per cent of Toombak dippers-lesions showed dysplastic cells. The grizzle and the cotton- white clinical presentations are associated with high-risk dysplasia. A significant relationship was found between the clinical presentation and the AoC. No significant relationship was found between the clinical presentation and the Impact of Time Duration (TD), in terms of life-time duration of dipping, number of dippings/day, dip-duration and the Estimated Contact Hours (ECH).

Induced cell-autonomous neutropenia systemically perturbs hematopoiesis in Cebpa enhancer-null mice

The transcription factor C/EBPa initiates the neutrophil gene expression program in the bone marrow. Knockouts of the Cebpa gene or its +37kb enhancer in mice show two major findings: (1) neutropenia in bone marrow and blood; (2) decrease in long-term hematopoietic stem cell (LT-HSC) numbers. Whether the latter finding is cell autonomous (intrinsic) to the LT-HSCs or an extrinsic event exerted on the stem cell compartment remained an open question. Flow cytometric analysis of the Cebpa +37kb enhancer knockout model revealed that the reduction in LT-HSC numbers observed was proportional to the degree of neutropenia. Single cell transcriptomics of wild type mouse bone marrow showed that Cebpa is predominantly expressed in early myeloid-biased progenitors, but not in LT-HSCs. These observations suggest that the negative effect on LT-HSCs is an extrinsic event caused by neutropenia. We transplanted whole bone marrows from +37kb enhancer deleted mice and found that 40% of the recipient mice acquired full blown neutropenia with severe dysplasia and a significant reduction in the total LT-HSC population. The other 60% showed initial signs of myeloid differentiation defects and dysplasia when they were sacrificed, suggesting they were in an early stage of the same pathological process. This phenotype was not seen in mice transplanted with wild type bone marrow cells. Altogether, these results indicate that Cebpa-enhancer deletion causes cell autonomous neutropenia, which reprograms and disturbs the quiescence of HSCs, leading to a systemic impairment of the hematopoietic process.

Anti-leukemogenic Efficacy of Aloe vera Gel on Benzene-induced Leukemia in Wistar Rats

Backgroud: The toxicity of benzene leading to leukemia induction has been well documented in animal model. Aloe vera is a succulent perennial evergreen flowering plant used traditionally in the treatment of jaundice and was found to have potent cytotoxic effect against HL60 human acute myeloid leukemia. The present study investigated the in vivo chemoprotective effects of Aloe vera gel on benzene-induced leukemia in rats. Methodology: Leukemia was induced in male Wistar rats of 80-90g weight by intravenously administered 0.2ml benzene solution alternate days for four weeks. Following induction, leukemic rats and normal baseline control rats were randomly assigned into four experimental groups of 6 animals each as follows: Group CTRL (control), normal baseline control rats; Group AVG (Aloe vera gel), normal baseline rats treated with Aloe vera gel (150 mg/kg) for 7 days, Group LKR (leukemic rats), untreated leukemic rats serving as leukemia control and Group LKR + AVG, leukemic rats treated with Aloe vera gel (150 mg/kg) for 7 days. Results: Leukemic rats showed altered hematology and morphological deformations such as anisocytosis, poikilocytosis and blast cells occurrence in peripheral blood. Also hypercellularity, severe dysplasia and significantly elevated micronucleated polychromatic erythrocyte were observed in marrow of leukemic rats. Moreover, benzene caused a significant elevation in plasma level of advanced oxidation protein products (AOPPs) with concomitant reduction in total sulfhydryl and arylesterase activity. However, treatment with Aloe vera gel restored blood hematology to near normal and mitigated the deformities in blood cell morphology induced by benzene. Aloe vera supplementation also effected a disappearance of dysplasia and diminution in the frequency of micronucleus in the bone marrow of treated leukemic rats. It also enhanced plasma antioxidant capability by restoring sulfhydryl content and arylesterase activity of the blood and abrogated the increase in plasma content of AOPPs. Conclusion: Overall, Aloe vera gel offered chemoprotective effect on Benzene-induced leukemia in rats.

Probability of Transition of Normal Esophageal Mucosa and Precancerous Lesion to the Esophageal Cancer

Background: To estimate the transition probabilities of esophageal cancer（EC） and its precancerous lesions by Markov model, which could provide important information for EC screening about choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models by comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real-world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusions: An esophageal cancer transition model in high-risk areas of China has been established with validity. It could be a point of reference for further economic evaluation and policy formulation of esophageal cancer screening.

Risk Models Based On Populations In High-Risk Areas of Oesophageal Cancer In China For Improving The Oesophageal Cancer Diagnosis Rate

Background: To improve the diagnostic efficiency of early oesophageal cancer, it is of great significance to develop an effective risk prediction model. This study aimed to identify a high-risk population with oesophageal squamous cell carcinoma (ESCC) based on a population screening model.Methods: From 120 target townships randomly selected from 150 villages selected in Nanchong City, Sichuan Province, China, from Jan 2016 to Sep 2019, a total of 6409 subjects were screened. Each patient underwent standard endoscopy and narrow band imaging (NBI) and iodine staining indicator biopsies to evaluate oesophageal cancer and precancerous lesions. Before endoscopy, the subjects completed a questionnaire about ESCC risk factors. Variables were evaluated by univariate analysis, and variables significantly related to ESCC were extracted by using a logistic regression model. We used the Akaike information criterion to develop the final model structure and the coding form of variables with multiple metrics. We developed two sets of models to define severe dysplasia and above (SDA) and moderate dysplasia and above (MDA) as prognostic events, respectively. Results: The areas under the receiver operating characteristic curve (AUROC) were0.896 (95%CI, 0.888-0.903) and 0.825 (95% CI, 0.816-0.835) for our SDA and MDA models, respectively. MDA-related and SDA-related factors included age, sex, cigarette smoking, alcohol drinking, pharyngeal foreign body sensation, swallowing obstruction, pain behind the sternum, and discomfort behind the breastbone.Conclusions: we developed an easy-to-use model to identify individuals with high risk of dysplasia or oesophageal cancer in high-risk areas of oesophageal cancer in China.

803 Management of An Intra-Oral Resection with Integra® Dermal Regeneration Template – Worth A Bite?

Introduction There are a spectrum of treatment options available for reconstruction of oral mucosal defects including secondary healing, skin grafts, local flaps and microvascular free flaps. We present the use of an alternative intra-oral reconstruction with Integra® Dermal Regeneration Template. Case Report An 85-year-old patient with a severe gag reflex and history of oral cancer presented with biopsy proven severe dysplasia of the right palate extending to the hamular notch. She was treated with wide local excision, extraction of teeth, buccal fat pad advancement for closure of an oral-antral communication and placement of Integra® Dermal Regeneration Template. Discharge was possible the same day as the patient was able to eat and had minimal pain. Discussion Integra® Dermal Regeneration Template is a bilayer wound matrix consisting of silicone in the outer layer with bovine collagen and glycosaminoglycan from shark cartilage in the inner layer. Oral cancer predominantly affects the older population, and this method can reduce surgical time, remove donor site pain, reduce post-operative pain and avoid use of a cover plate where a strong gag reflex was present. The area heals quickly and aids quick restoration of oral function. Conclusion Integra® Dermal Regeneration Template has been used for head and neck defects with good outcomes. It is being increasingly used intra-orally with good outcomes, suggesting a further application of the material with advantages over traditional techniques in specific patient groups.

Dysplastic Patellofemoral Joints Lead to a Shift in Contact Forces: A 3D-Printed Cadaveric Model

Background: The distribution of contact forces across the dysplastic patellofemoral joint has not been adequately quantified because models cannot easily mimic the dysplasia of both the trochlea and the patella. Thus, the mechanical consequences of surgical treatments to correct dysplasia cannot be established. Purpose/Hypothesis: The objective of this study was to quantify the contact mechanics and kinematics of normal, mild, and severely dysplastic patellofemoral joints using synthetic mimics of the articulating surfaces on cadavers. We tested the hypothesis that severely dysplastic joints would result in significantly increased patellofemoral contact forces and abnormal kinematics. Study Design: Controlled laboratory study. Method: Patellofemoral dysplasia was simulated in 9 cadaveric knees by replacing the native patellar and trochlear surfaces with synthetic patellar and trochlear implants. For each knee, 3 synthetic surface geometries (normal, showing no signs of dysplasia; mild, exemplifying Dejour type A; and severe, exemplifying Dejour type B) were randomized for implantation and testing. Patellar kinematics and the sum of forces acting on the medial and lateral patellar facets were computed for each knee and for each condition at 10° increments from 0° to 70° of flexion. Results: A pronounced lateral shift in the weighted center of contact of the lateral facet occurred for severely dysplastic knees from 20° to 70° of flexion. Compared with normal geometries, lateral patellar facet forces exhibited a significant increase only with mild dysplasia from 50° to 70° of flexion and with severe dysplasia at 70° of flexion. No measurable differences in medial patellar facet mechanics or joint kinematics occurred. Conclusion: Our hypothesis was rejected: Severely dysplastic joints did not result in significantly increased patellofemoral contact forces and abnormal kinematics in our cadaveric simulation. Rather, severe dysplasia resulted in a pronounced lateral shift in contact forces across the lateral patellar facet, while changes in kinematics and the magnitude of contact forces were not significant. Clinical Relevance: Including dysplasia of both the patella and trochlea is required to fully capture the mechanics of this complex joint. The pronounced lateralization of contact force in severely dysplastic patellofemoral joints should be considered to avoid cartilage overload with surgical manipulation.

Assessment of Contralateral Biopsy Technique for Improving Tissue Changes in Patients with Tongue Malignancy

Background: Oral cancer is one of the most common type of head and neck cancer, with a 5 year survival rate of < 50%. One of the major problems of oral cancer include the late stage of disease at the time of diagnosis. Mirror image biopsy is a new technique that can be used for detection of early changes in the oral mucosa. Aim of the study: To histologically assess the reflect copy biopsy occupied from clinically usual observing mucosa at consistent contralateral anatomical place to the main lesion in patients identified with tongue squamous cell carcinoma to notice any indication of arena alteration in oral mucosa. Materials and methods: Seven patients diagnosed with squamous cell carcinoma of the tongue underwent reflect copy biopsy from clinically usual observing mucosa at consistent contralateral anatomical place to the main lesion. The reflect copy biopsy example were exposed to histopathological check. Results: of the seven patients included, four were male and three were female, with an age range from 45 years to 64 years (median 54.5 years). One of the biopsies revealed severe dysplasia and six-revealed hyperplasia of the epithelium. Conclusion: Mirror image biopsy is a useful tool to detect the early field changes in oral mucosa in order to prevent further progression to oral cancer.