METHOD AND PROCEDURE TO DETECT ORAL TISSUES WITH HIGH-RISK MOLECULAR PROFILES

Abstract

A diagnostic method for detecting high risk oral tissue which due to chromosome allelic loss and may have developed or will potentially develop into carcinoma in situ and carcinoma by using a staining agent. A set of questionnaire that identifies high-risk individual and high-risk lesions and helps to reduce false positive for the diagnosis of oral tissue with high-risk molecular profile. A recording sheet with oral cavity diagram that helps to record the examination results more accurately and reduce the examination errors. This improved method has a broad application that can be used to screen the oral tissues with high risk molecular profile from hyperplasia, dysplasia, erythroplasia, leukoplasia, leukoerythroplasia, erythroleukoplasia, verrucous lesion, ulcerative lesion, carcinoma in situ, and carcinoma.

Description

BRIEF DESCRIPTION OF THE INVENTION

Briefly, in accordance with the invention, I provide methods and improved procedures of screening patients, using an oral staining agent (toluidine blue) as a tool, for high risk oral tissue which due to chromosome allelic loss (or, Loss of Heterozygosity, LOH) and may have developed or will potentially develop into carcinoma in situ and carcinoma.

The method includes a kit that can be used for a broader application to screen patients for high risk molecular profile for hyperplasia, dysplasia, erythroplasia, leukoplasia, leukoerythroplasia, erythroleukoplasia, verrucous lesion, ulcerative lesion, carcinoma in situ, and carcinoma.

In accordance with one embodiment of the invention I provide an easy-to-use packaged diagnostic kit for performing routine screening procedure to detect high-risk molecular profile that may have developed or potentially develop into carcinoma in situ and carcinoma. The improved procedure includes the steps of sequentially applying preselected volumes with two testing reagents of preselected concentrations to suspected oral lesion sites, with 2 or 3 or more repeats to reduce the false positive.

In accordance with another embodiment of the invention, the kit includes a questionnaire sheet to identify the high-risk individuals and reduce the false positive. Since identifying high-risk individuals or high-risk behaviors would significantly rule out the false positive, the questionnaire would help achieve a more accurate diagnosis for screening high-risk oral tissues, some of which even appear normal.

In accordance with yet another embodiment of the invention, the kit also includes a recording sheet, which will help clinician to focus on high-risk sites and easily and accurately record the result, to avoid some examination errors, also reduce the false positive which due to the examination error in screening patients for high risk oral tissue. Since the repeated examination would be common for many screenings, it would be idea to record the previous results accurately to compare with the results later examined at different time periods. Otherwise, examination errors may occur, either missing the high-risk lesion or including wrong one, especially for those patients who had multiple sites of oral lesions.

Using this improved method and procedure, combined with questionnaire and recording sheet, the false positive can be as low as 2%, if performed well. To reduce the false negative, an occasional equivocal circumscribed light-blue stain should be considered positive.

Also, the kit with packaged form provides convenience for clinician to perform office routine screening by compose only two bottles (rinse and stain solution), and the disposable cups with 10 cc indicator line for easy and accurate dispensing.

If oral or oropharyngeal cancer is identified, further diagnosis should be performed to check the larynx, hypo pharynx, esophagus, and lungs to rule out multiple primary cancers. The patient should also have yearly routine checks.

DESCRIPTION FOR DRAWINGS

DRAWING. 1: The questionnaire to help reduce false positive. The Key questions are most important questions to identify the high-risk individuals. Optional questions are either minor factor to determine high-risk individuals or to address the unique risk factors for specific populations. For example, in most of Southeast Asia countries, many local people have a habit to chew Betel nut (also known as Pinang or Areca nut), which will significantly increase the risk to have oral cancer. So, it is appropriate to add such an optional question when doing examination at Southeast Asia area.

DRAWING. 2: The recording sheet has pictures that can clearly locate the staining result more accurately than pure description. This will better record the examination result to reduce the examination errors, since the examination usually will be repeated and the results obtained at different time will be compared.

DRAWING. 3: Kit of all items in one box 10, including one big bottle of rinse solution 11 and one small bottle of staining solution 12; disposable cups 13 with volume indicator line; and document bags 14 which can hold the questionnaire sheet, the recording sheet and other necessary documents.

Claims

1. A diagnostic method of detecting high risk oral tissue which have chromosome allelic loss and may have developed or potentially develop into carcinoma in situ and carcinoma by using toluidine blue staining solution, wherein said staining solution is an aqueous glacial acetic acid solution containing a 1% toluidine blue, also containing but not limiting to ethyl alcohol, hydrogen peroxide, flavoring additives and water, and by including steps of sequentially rinsing the oral cavity with the staining solution, and rinsing the oral cavity with a rinse solution to remove unstained toluidine blue, wherein said rinse solution mainly contains of glacial acid, and also contains but not limits to ethyl alcohol, sodium benzoate, flavoring additives and water, with the detailed examination procedures as following: (a) rinsing the mouth of the patient with rinse solution for a period of about 20 seconds followed by a similar rinse with water twice for about 20 seconds;(b) rinsing the mouth of the same patient with 10 cc. staining solution for about 1 minute while simultaneously gargling; and(c) rinsing with 10 cc rinse solution for about 1 minute followed by a second rinse with rinse solution for 20 seconds, and followed a water rinse.(d) performing a second repeat in 10-20 days (preferred 15 days), followed with a biopsy if both results are positive, or followed with no biopsy if not double positive but with a third repeat in 3-6 months (preferred 4 months).

2. An examination kit including questionnaire that is used to identify high-risk individuals and reduce the false positive during diagnosis, said questionnaire comprising following key questions with other optional questions: (a) Have you had any neck and head cancer history before?(b) Have you had heavy smoking history (more than 10 cigarettes per day, or use smokeless tobacco, cigars or pipes)?(c) Have you had heavy drinking history (more than three whiskey equivalents per day)?(d) Have you had oral ulcer for continuous 6 months, or persistent erythroplastic lesions or erythroplakia within a leukoplasia?(e) Does the lesion occur on the floor of the month, or the ventrolateral tongue, or the soft palate complex?Said optional questions used to address the minor risk-factors or specificity for the screened population can be exampled but not limited to followings:1) Do you have habit to chew Betel nut (or Beetal nut, or Pinang, or Areca nut, or Paan, or Gutkha)?2) Are you older than 40?3) Do you notice any white, red, or dark lesions anywhere in the mouth?4) Do you have adequate oral and personal hygiene?5) Do you have oral habits such as cheek or lip biting?6) Do you have repeated or unusual bleeding anywhere in the mouth?7) Do you have difficulty swallowing or chewing?8) Do you have any swelling, lumps or bumps in mouth?9) Do you wearold or ill-fitting dentures or have chronic irritation from dentures?10) Do you have vitamin deficienty, or eat hot or spicy foods, or sharp teeth?11) Do you have family history of cancer?.

3. An examination kit including a recording sheet with oral cavity diagram to better record the location of stained lesion, said diagram can accurately locate the stained lesions within oral cavity, which can assist clinician to make correct recording for the stained result to avoid such examination error thereof, said recording will be used to compare the repeated staining results to get a better diagnosis.

4. An examination kit in one box, including two bottles of staining solution and rinse solution; disposable cups with volume indicator line; the questionnaire and the recording sheet; and other necessary documents, to make clinician easier to perform screen test.