Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application

Study Overview
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Brief Summary
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Early detection and treatment of precancerous lesions are the pillars of cervical cancer prevention. Cervical Intraepithelial Neoplasia (CIN) is a precancerous lesion that histologically can be found in one of three stages of development; CIN-I (low grade), CIN-II, or CIN-III (collectively called high grade), depending on the proportion of the depth of the lesion to the thickness of the cervical epithelium. The higher the degree of CIN, the deeper the pre-cancerous lesions are found in the epithelial lining of the cervix. Therefore, from the point of view of precancerous lesions treatment, its effectiveness will be determined by the ability to eradicate all high-grade lesions. In other words, it has an effect that can reach depths beyond the depth of the high grade lesion. According to a study in the US (1982), as many as 99.7% of CIN-III cases had a lesion depth of less than 4.8 millimeter. Furthermore, a Netherlands study (1990) stated that as many as 99.7% of CIN-III cases had a maximum lesion depth of 3.6 millimeters. While in subjects from developing countries, study from Peru (2018) showed that 93.5% of CIN-III cases have a lesion depth of less than 5 millimeters. Based on the results of these studies, a treatment for CIN can only be said to be effective if it can create a therapeutic effect which can reach depths of 4-5 millimeters in cervix epithelial. Trichloroacetic acid (TCA) is an acetic acid analogue, which has long been known as a chemical peel and also frequently used to treat genital ward and precancerous skin lesions. The effect of TCA therapy is the destruction of the epithelium forming epithelial necrosis, followed by re-epithelialization of the supporting tissue and stimulation of collagen synthesis within approximately in 24 hours. There are no studies regarding the depth of cervical necrosis that can be achieved by application of this solution to the cervix epithelial.

Detailed Description
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Primary Objectives: The purpose of this study is to determine the depth of epithelial necrosis in cervical tissue specimen after 85 percent TCA application on clinically normal cervix. Procedure: Patients will receive a single administration of 1-2 milliliter of 85 percent TCA in 24 hours before elective total hysterectomy surgery on indication other than cervical pathology. The 85 percent TCA will be applied topically onto the ectocervix and the endocervix canal with a cotton swab for 1-2 minutes. After surgery, cervical specimen will be fixated in formalin and sent for histopathologic examination.

Official Title
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Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application

Conditions
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Cervix; Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: 85% TCA Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal cervix without significant changes and must be tested negative for Visual Inspection Acetic-Acid (VIA) test (no acetowhite lesions are found) Participants are willing to participate voluntarily in this research by signing a consent form. Exclusion Criteria: Patients who finally have undergone sub-total or supra-vaginal hysterectomy. Any abnormalities found in postoperative cervical histopathology results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 85% TCA Group<br>Participants are subject who will undergo an elective total hysterectomy procedure for indications of gynecological organ abnormalities, whether benign, pre-cancerous, or malignant other than cervical pathology. The 85 percent TCA solution will be applied to participants cervical tissue 24 hours before surgery. | Drug: 85% TCA Solution<br>* TCA is an acetic acid analogue solution (CCl3COOH) which is formed from the reaction of acetic acid (CH3COOH) with chlorine (3Cl2). High concentrations (85 percent) of this solution can penetrate deeply into the epidermis-dermis layer and cause cells necrosis. This solution (1-2 milliliter) will be applied to participants cervical tissue (ectocervix and endocervix) using cotton swab for 1-3 minutes.<br>* Other names: CCl₃COOH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depth of Cervical Epithelial Ablation | Based on damage to the cervical epithelium, both squamous (ectocervix), transformation zone, and columnar (endocervix) epithelium. Destruction of base membrane and stromal tissue will also be evaluated. Microscopic evaluation using a micrometer on a 10 times magnification eyepiece. The deepest ablative destruction in epithelial, base membrane, and stromal tissue will be recorded and stated in millimetres. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores | Measured immediately after application of the 85 percent TCA solution with Visual Analogue Scale (VAS) score. Highest score means worse ouctcome. Minimum score is 0 (No Pain) and maximum score is 10 (worst pain). | 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trichloroacetic Acid (TCA), Depth of Necrosis, Cervix Intraepithelial Neoplasia