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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2021

Detailed Description

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.

Interventions

  • Drug: 85% TCA Solution
    • 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.

Arms, Groups and Cohorts

  • Experimental: 85% TCA Group
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Depth of Cervical Epithelial Ablation
    • Time Frame: 30 days
    • 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.

Secondary Measures

  • Pain Scores
    • Time Frame: 10 minutes
    • 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).

Participating in This Clinical Trial

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.

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Indonesia University
  • Collaborator
    • Dr Cipto Mangunkusumo General Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Prof. Dr. dr. Laila Nuranna, SpOG-K, Professor – Indonesia University
  • Overall Official(s)
    • Laila Nuranna, Professor, Principal Investigator, Indonesia University
  • Overall Contact(s)
    • Dolly N Lubis, Ob/Gyn, +628122436967, doelhappy@gmail.com

References

Boonstra H, Aalders JG, Koudstaal J, Oosterhuis JW, Janssens J. Minimum extension and appropriate topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia. Obstet Gynecol. 1990 Feb;75(2):227-31.

Abdul-Karim FW, Fu YS, Reagan JW, Wentz WB. Morphometric study of intraepithelial neoplasia of the uterine cervix. Obstet Gynecol. 1982 Aug;60(2):210-4.

Taxa L, Jeronimo J, Alonzo TA, Gage J, Castle PE, Cremer ML, Felix JC. Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis. J Low Genit Tract Dis. 2018 Jan;22(1):27-30. doi: 10.1097/LGT.0000000000000355.

Brodland DG, Cullimore KC, Roenigk RK, Gibson LE. Depths of chemexfoliation induced by various concentrations and application techniques of trichloroacetic acid in a porcine model. J Dermatol Surg Oncol. 1989 Sep;15(9):967-71.

Mariategui J, Santos C, Taxa L, Jeronimo J, Castle PE. Comparison of depth of necrosis achieved by CO2- and N2O-cryotherapy. Int J Gynaecol Obstet. 2008 Jan;100(1):24-6. Epub 2007 Sep 25.

Adepiti AC, Ajenifuja OK, Fadahunsi OO, Osasan SA, Pelemo OE, Loto MO. Comparison of the depth of tissue necrosis between double-freeze and single-freeze nitrous oxide-based cryotherapy. Niger Med J. 2016 Jan-Feb;57(1):1-4. doi: 10.4103/0300-1652.180561.

Geisler S, Speiser S, Speiser L, Heinze G, Rosenthal A, Speiser P. Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia. Obstet Gynecol. 2016 Feb;127(2):353-9. doi: 10.1097/AOG.0000000000001244.

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