A CASE OF CERVICAL INTRAEPITHELIAL NEOPLASIA - MANAGEMENT THROUGH AYURVEDA

Introduction – Cervical cancer is the 2nd most leading prevalent cancer in India. There are an estimated 123,000 new cases of cervical cancer in India every year with 67,000 deaths in women alone. Cervical cancer in Recent studies shows that screening of cervical cancer reduces the disease incidence and disease mortality by 50%. Low- grade squamous intraepithelial lesion (LSIL) is a common abnormal result on a Pap smear cervical test. It’s also known as mild dysplasia. Methodology – Here is a case report of a patient aged 26yrs with complaints of white discharge per vagina with severe itching, on routine cervical screening investigations found to have Low grade squamous intraepithelial neoplasms. She was treated with Ayurvedic sthanika chikitsa (Local therapies) such as Yoni prakshalana (Vaginal douching), and Yoni pichu (Vaginal tamponing) for 7 days along with shaman chikitsa. Later PAP smear was repeated after 1 month of follow up and found to have negative for intraepithelial neoplasia. And there was relief in the symptoms following treatment. Results- In this case, there was a relief of symptoms and on follow up when Pap smear was repeated, there was negative for intraepithelial neoplasia. Ayurvedic treatment modalities such as Sthanika chikitsa which includes yoni prakshalana and Yoni Pichu are the line of treatment for various gynecological problems and help in reducing mortality and morbidity caused due to cervical cancer in India. Discussion- Here Low-grade squamous Intraepithelial neoplasia can be considered as the Sanchaya avastha and hence diagnosing the disease in its Sanchaya avastha i.e mild dysplasia, is important. During Sanchaya avastha there is localized neoplastic changes of cervical cells and there is Manifestation of Low-grade Intraepithelial Neo- plasia. In the later stages of Kriyakala (Stages of disease manifestation) the neoplasia turns into metastasis and further differentiation occurs which Manifests all the symptoms of Cervical Cancer. Hence treatment modalities such as Yoni prakshalana and yoni pichu helps in preventing later conditions such as cervical cancer. Keywords: Cervical Cancer, LSIL, Ayurveda, Sanchaya

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.

Microinvasive Oral Squamous Cell Carcinoma of Gingiva: An Enigma

Microinvasive oral squamous cell carcinoma (MIOSCC) of gingiva is an early stage relatively ‘thin’ tumour without invasion of deep tissues. A 55-year old male reported with the chief complaint of gum swelling in lower right back jaw region for one month. On examination, diffuse, unscrappable, white homogenous plaque extending from 35 to 48 was present with a firm, sessile gingival growth approximately eight millimetre in diameter. A provisional diagnosis of verrucous leukoplakia was made. Hence, biopsy was performed which confirmed MIOSCC and mild dysplasia for different sites. The patient is on regular follow-up and with no signs of recurrence.

p53 & Cyclin D1 expression in surgically resected clear margins of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most well-known malignancies that affect the human population worldwide. The early diagnosis and early intervention of OSCC help improve the survival rate of the patients. The tumour free surgical margins are a positive prognostic factor for recurrence-free survival. The molecular markers can be used to detect the tumour free surgical margins. Aim: The aim of the study is to evaluate the expression of p53 & Cyclin D1 marker in resected surgical apparently clear margins and to correlate the p53 & Cyclin D1 expression with clinicopathological characteristics and patient outcome. Methods: The study population included retrospective cases of OSCC with apparently clear margins (2017-18) n=10 and Clinicopathological variables relevant to survival analysis were recorded. Finally, two margins were selected from each case, a total of 20 margins were included in this study. Paraffin-embedded wax blocks retrieved and tissue sections were made. Expression of cyclin D1 and p 53 was assessed by the immunohistochemical staining procedure Results: Positive expressions Cyclin D1 in 40% of mild dysplasia margins and 60% in clearance adequate margins were present. p53 expression was seen in 16% of mild dysplasia margins and 84% in clearance adequate margins. The expression of p53 and Cyclin D1 molecular markers are noted in the basal & parabasal layer of epithelium. Conclusion: Molecular markers could play a more reliable method for the assessment of dysplasia at the margins.

Enhanced detection of oral dysplasia by structured illumination fluorescence lifetime imaging microscopy

We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63).

Expression of e-cadherin and vimentin in lesions of oropharynx

Background: Oral squamous cell carcinoma is the 6th most common malignancy in the world and ranks as first in males in Indian sub-continent. Vimentin is an intermediate filament found in mesenchymal cells and e-cadherin is an adhesion molecule found in epithelial cells. The objective of the study is to evaluate the expression of e-cadherin and vimentin in lesions of oropharynx and to assess the sensitivity, specificity and positive predictive value of e - cadherin and vimentin in oropharyngeal squamous cell carcinoma (OPSCC), against routine H and E stained histopathological diagnosis.Methods: 100 oropharyngeal biopsy specimens taken and routine H and E stained histopathological slide diagnosis made. E-cadherin and vimentin expression studied in OPSCC, moderate to severe dysplasia, mild dysplasia and benign cases and its sensitivity, specificity, positive predictive value and negative predictive value analysed using appropriate statistical tools.Results: Vimentin positivity was observed in 70 out of 79 OPSCC, 2 out of 3 cases of moderate - severe dysplasia, 0 out of 2 mild dysplasia and 2 out of 16 benign lesions. Out of 79 cases of OPSCC, 15 were e-cadherin negative, 27 showed low and 37 cases showed high membraneous positivity.Conclusions: We observed a significant decrease in e-cadherin membrane expression from dysplasia to carcinoma insitu to invasive carcinoma and a significant increase in vimentin expression with progression of the tumor. E-cadherin is a good prognostic marker whereas vimentin expression indicates a poor prognosis.

Estimation of The Transitional Probability Among Esophageal Cancer and Its Precancerous Lesions

Background: To estimate the transition probabilities of esophageal cancer (EC) and its precancerous lesions during the process of canceration by Markov model, which could provide important information for EC screening with regard to 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 through 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.Conclusion: The estimating transition probabilities of EC and its precancerous lesions were reliable and could be used to address questions such as the optimal screening frequency, screening intervals, and health economic evaluation of screening strategies.

LOW-GRADE DYSPLASIA, ENDOSCOPIC PREDICTORS, MANAGEMENT TACTICS

Almost all East Asian strains and 60% of Western H. pylori strains are of cagA +. The infected patients develop a more pronounced inflammation with ulceration of stomach, and also are under a higher risk of development of cancer.Objective: to improve the informative value of dysplasia diagnosis by combining white light endoscopy with chromoscopy, supplemented by target brush biopsy with cytological examination.Methods and materials: for the period from 2016 to 2018, the study included 41 patients undergoing examination and treatment of chronic gastritis. The analyzed cases included 16 (39%) men and 25 (61%) women. The age of the patients ranged from 19 to 86 years. All patients underwent esophagogastroduodenoscopy, chromoendoscopy with 0.5% methylene blue, brush biopsy (scraping with a nylon brush). At least two brush preparations were obtained: body of the stomach, antrum, scraping was also made on the surface of erosions and areas of atypical structure of the epithelium. Brush preparations were sent for cytological examination. Results: esophagogastroduodenoscopy revealed erosions in 37 (90.2%) patients, in 6 cases (14.6%) among them spontaneous bleeding was determined. In 23 (56%) patients visual signs of atrophic gastritis were noted. Cylindrical epithelium of the intestinal type was revealed in 25 patients (61%) using methylene blue.The cytological examination of the brush preparation showed proliferation of the integumentary epithelium with signs of mild dysplasia in all cases, intestinal metaplasia was revealed in 27 patients (65.8%), H. Pylori was confirmed in 38 patients (92.6%).Conclusion: chromoscopy and brush biopsy are simple and affordable methods, and their integration into routine endoscopy increases the informative value of the study, namely, allows detection of precancerous lesions of mucosa.

The Evaluation of Trochlear Osseous Morphology: An Epidemiologic Study

Objectives: The purpose of this study is to investigate the prevalence of the trochlear dysplasia in our study population. Methods: We obtained 692 skeletally mature femoral specimens from the [Blinded Institution], [Blinded Collection]. Five observers were asked to evaluate each specimen for trochlear dysplasia on a scale between 0 and 3 (0 – normal/no dysplasia; 1 – mild dysplasia; 2 – moderate dysplasia; 3 – severe dysplasia). Each observer made initial evaluations for interobserver reliability. Each observer then re-evaluated each specimen one month later to determine intraobserver reliability. We evaluated inter and intraobserver reliability utilizing intraclass correlation coefficient (ICC). All statistics were performed with SPSS v.25 (IBM, USA). Results: The interobserver ICC of first and second evaluation of all observers were found to be 0.906 [0.894-0,916] and 0.904 [0.892-0.915], respectively. The intraobserver ICC of observers were as follows: Reviewer1: 0.799 [0.771-0.825]; Reviewer2: 0.686 [0.645-0.724]; Reviewer3: 0.808 [0.781-0.832]; Reviewer4: 0.787 [0.757-0.814]; Reviewer5: 0.778 [0.747-0.806]. These results show intra and interobserver correlation was good to excellent. The percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia for first evaluation, by reviewer, are as follows: Reviewer 1: 82.7%, 12.1%, 4.0%, 1.2%; Reviewer 2: 37.3%, 26.2%, 27.5%, 9.1%; Reviewer 3: 57.9%, 28.0%, 12.1%, 1.9%; Reviewer 4: 64.2%, 25.6%, 7.7%, 2.6%; Reviewer 5: 65.6%, 14.9%, 12.3%, 7.2%. The percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia for second evaluation, by reviewer, are as follows: Reviewer 1: 78.8%, 16.6%, 3.6%, 1.0%; Reviewer 2: 40.3%, 26.4%, 23.3%, 10.0%; Reviewer 3: 42.2%,35.1%, 18.8%, 3.9%; Reviewer 4: 57.4%, 31.9%, 8.2%, 2.5%; Reviewer 5: 73.7%, 8.2%, 9.7%, 8.4%. In total, the percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia were 60.00%, 22.51%, 12.72%, 4.77%; respectively. Conclusions: This study shows that although there was no absolute criteria to grade trochlear dysplasia, observers had similar opinions on the degree of dysplasia. Also, our cohort shows that moderate to severe dysplasia is not uncommon as it is present in around 17% of knees in our cohort. This is the first epidemiologic study evaluating the prevalence of trochlear dysplasia in the normal population.

Importance of Ki-67 Labeling in Oral Leukoplakia with Features of Dysplasia and Carcinomatous Transformation: An Observational Study over 4 Years

Background Early detection of dysplastic changes within oral potentially malignant disorders is the mainstay to prevent oral cancer. Ki-67 is one of the most useful antigens in this purpose. Aims The study aims were to recognize and mutually compare the proliferative status of idiopathic oral leukoplakia (OL) patches, which presented through different forms of dysplasia and carcinoma. Settings and Design In 4 years of observation, cumulatively 140 OL lesions were included for examination. The wholesome Ki-67 labeling scores in each of the subgroups were calculated. Subjects and Methods The World Health Organization recommended histopathological classification was used to categorize the dysplastic and malignant lesions. Paraffin-embedded tissue sections were processed for Ki-67 immunostaining. The labeling indices (LIs) were quantified semiquantitatively at the site of maximal reactive cells on tissue sections. Statistical Analysis The statistical comparison was performed by means of the SPSS software (Version 16.0 SPSS Inc.). A p-value < 0.05 was considered as the benchmark for statistical significance. Results A steady and significant increment in Ki-67 expression was discovered from dysplastic to malignant OL patches compared with normal mucosa. The labeling differences were significant between normal mucosa and mild dysplasia, as well as between mild, moderate, and severe dysplasia. However, the expression did not differ significantly with the severity of oral cancers. Conclusions Ki-67 is a useful molecular marker of carcinogenesis in OL. It also serves worthwhile in separating marginally dysplastic lesions, such as mild dysplasia or verrucous carcinoma from their benign epigones.