WO2009072856A1

WO2009072856A1 - Vaginal speculum including a system and a specific method for diagnosing lesions caused by the human papillomavirus in the female genital tract

Info

Publication number: WO2009072856A1
Application number: PCT/MX2007/000147
Authority: WO
Inventors: Joel Gerardo DÍAZ SÁNCHEZ; José Gerardo Zertuche Zuani; Cala Hegde
Original assignee: Diaz Sanchez Joel Gerardo; Zertuche Zuani Jose Gerardo; Cala Hegde
Priority date: 2007-12-04
Filing date: 2007-12-04
Publication date: 2009-06-11

Abstract

The high incidence of cases of cervical-uterine cancer reflects the lack of mass detection programmes and of low-cost medical methods and equipment that facilitate early detection of the disease even among the most remote populations. The invention relates to a very-low-cost novel diagnostic speculoscopy system for the detection of lesions caused by human papillomavirus (HPV) in the female genital tract. Said device weighs barely 200 grams. The novel invention combines a vaginal speculum with a fluorescence system specific to the marker of lesions caused by HPV. Said system contains a nitrogen gallium light-emitting diode (LED) that emits the blue light required to excite the marker in the diseased epithelium, the image of the lesions being observed with a yellow barrier filter. The electricity supply source used to power the illuminator is a long-life rechargeable battery, which enables the device to be used anywhere in the world.

Description

Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract.

Technical sector: Optical and opto-electronic medical instruments, gynecological instruments and methods for diagnosing lesions caused by Human Papillomavirus (HPV) in the female genital tract through visual methods. Emerging technologies in dysplasias, Optics and Medical Physics.

Background of the invention:

The viral genus Papilloma is too extensive, they are DNA viruses that infect many species of animals, including Man. There are more than 100 types of these known as Human Papillomavirus (HPV).

Interest in these viruses has gradually increased since 1970, when they were first assigned a role in the etiology of Cervical Cancer (CaCu).

Cervical Cancer Uterine is a common class of cancer in women, it is a change of the cells of the epithelial tissue of the cervix, as well as the vaginal and vulvar walls. These cells are initially normal and gradually become precancerous. Before cancer cells are found in the cervix, their tissues undergo changes and abnormal cells begin to appear; Process known as Dysplasia or Cervical Intraepithelial Neoplasia (NIC).

There are more than 30 viral types of HPV, which have the ability to infect the female genital tract, of these types there are benign viruses called "low risk", and other oncogenic called "high risk".

Cervical-Uterine Cancer is one of the most common cancers in women. The figure of 500,000 cases per year is estimated worldwide. About 80% of these occur in developing countries. The high incidence of cases reflects the poverty of massive cervical cancer screening programs (CaCu), as well as low-cost medical equipment and methods that facilitate early detection of the disease even in the most distant locations of the populations .

The vaginal speculum is one of the most used medical instruments. Every year millions of vaginal exams are performed worldwide. The name of the instrument used in any gynecological examination is: Vaginal speculum. This was invented many centuries ago, in the Talmud and in ancient documents from India dated 3,000 years ago, there are already descriptions of it. It was the Hebrews who introduced the use of the speculum to vaginally examine women suffering from female genital tract problems. Such an apparatus consisted of a mobile cylinder contained in a lead tube. The ancient Greeks and Romans had a speculum with vanes that could be separated by turning a nut, which they called: "diopter", derived from the Greek word "dioptra" which means spying or scrutinizing. The speculum arrived in Europe through Arab medicine while maintaining the form and name of the Roman diopter.

In the eighteenth century it began to be called speculum perhaps because it has to do with the fact that light enters the vagina through a mirror or possibly the properties of the metal used.

The most commonly used vaginal speculums are Graves and Pederson's, disposable or sterilizable.

The technique used for observation through the correct handling of the speculum is called speculacopy, which consists of its introduction into the vagina to observe the vaginal wall and the cervix. Speculoscopy is considered within gynecology as a direct visualization inspection method.

The cervix or Portio is the horizon of the examination with the speculum and that is where the signs of the injuries caused by the Human Papillomavirus (HPV) can be found, which have been increasing in the population during the last 15 years, so It is called as an emerging disease. Previous Technique:

There are 3 important pathways for the diagnosis of female genital tract diseases: modifications to cytological techniques, various molecular biology tests and new medical instruments such as: Optical coherence tomography, all of which have high costs.

Current State of the Art

In the current state of the art, some authors mention that speculoscopy refers to the method of visual inspection of the cervix using the acetic acid test and illuminating with bright white chemiluminescent light. This technique is currently only considered for research purposes and is not attached to massive cervical cancer screening programs (CaCu).

Another author from India mentions in a Mexican magazine that speculacopy using bright light and the application of vinegar in the uterine cervix has been able to detect dysplasia in an area of India, however this study is still under development.

Issue:

The Pap smear since the middle of the last century has helped prevent cervical cancer worldwide, but its reliability is not as desired.

As mentioned earlier cervical-uterine cancer is common among woman's cancers; a figure of 500,000 cases per year is estimated worldwide, but about 80% occur in developing countries, of which about 200,000 to 250,000 women die.

In the United States, the incidence of CaCu per 100,000 women is estimated at 8 and for Israel at 4.2, while for Peru and Mexico there are figures of 54.6 and 50 cases, respectively. Among the mortality due to neoplasms in the female population of Mexico, cervical-uterine cancer occupies the first position, with 12 to 16 deaths per day, since in the year 2000 4,604 deaths were registered according to the Ministry of Health.

Cervical-uterine cancer begins with changes in the cells of the epithelial tissue of the cervix, which gradually become abnormal cells called coilocytes and dyskeratocytes, which are typed at a microscopic level by a different Pap smear due to the presence of keratin and cell nuclei with increasing size; Its presence is an indicator of infection caused by HPV and is known by the term cervical intraepithelial dysplasia or neoplasia (CIN).

The advance of science and technology from the last century to date in the disease caused by the human papillomavirus has allowed the epidemiological window to decrease (period between the beginning of the presence of the etiologic agent and the appearance of the disease), without However, speculacopy alone is not currently located for massive population studies due to its low sensitivity and specificity in diagnosis and in the early detection of dysplasia and cervical-uterine cancer.

The lack in many offices and in the most remote places of an optimal, simple and cheap equipment as well as simple tests for the diagnosis of dysplasias have made doctors resort to laboratory tests and the use of sophisticated resources with great delays, in some cases, resulting in the period of uncertainty in the patient affecting her health even more.

Solution to the problem:

For all the above mentioned that currently speculacopy alone is not located for mass studies of the population due to its low sensitivity, this is why we have decided to combine it with a specific system and method to produce high power fluorescence in HPV-infected tissue through the use of a Light Emitting Diode ("LED") of Nitrogen Gallium that emits ultra-bright blue light with exact wavelength to excite and produce fluorescence in the tissue fluorochrome marker patient: Fluorescein isothiocyanate (FITC). To send this light directly to the cervix or portio we use an illuminator that is mounted by means of an adapter in the speculum in order to produce the phenomenon of fluorescence within the diseased cell tissue in the lesions of the cervix according to our method and visualizing the image of this fabric by means of a suppression filter or yellow barrier, obtaining this as a rich image of shades and contrasts on a dark background, drastically raising the image quality and having a highly reliable result. It is ideal for use in reproductive health control programs and is also an instrument of routine use for the doctor's office at public or private level in the control of their patients.

The vaginal speculum Graves, Pederson, Collin, Seyffert and Cusco, Trélat etc., disposable or sterilizable and its fluorescence excitation system using the Light Emitting Diode (LED) of Gallium Nitrogen for the diagnosis of lesions caused by the Virus of the Human papilloma in the female genital tract presented in the present invention aims, in addition to the above, to reduce medical costs and increase the benefit in the management of the patient.

Advantages of the invention:

The system to be patented has special and unique characteristics as well as competitive advantages:

1.- Fluorescence systems usually use two types of filters, an exciter and a barrier or cut filter, the cost of an excitation filter is high in addition to requiring an expensive lighting source, with the introduction In this fluorescence system using a Nitrogen Gallium Light Emitting Diode (LED) selected at a blue spectrum does not require the system of an exciter filter.

2.- The Nitrogen Gallium Light Emitting Diode (LED) gives us the blue wavelength, providing high quality light at a very low cost.

3.- The weight of the equipment is not more than 250 grams, which allows us to take it anywhere.

4.- The system works with rechargeable battery or disposable battery.

5.- The rechargeable battery holder contains connection adapters for 120-220 volts. 6.- The selection of the easy-to-use barrier filter in the system accepts the fluorescence technique with the specific fluorochrome for live tissues, so it allows the detection of the fluorochrome inside the diseased tissue in a single scan.

7.- Our technique has as one of its advantages that the fluorochrome "fluorescein isothiocyanate" is specific to react in the disease caused by the human papillomavirus, when reacting and producing fluorescence the lesions of the latter are seen in dark background, appearing color images full of nuances, selecting what the observer wants to see, this is the tissue injured by HPV.

8.- If you want to increase the image from the speculum, it can be combined with different instruments such as: magnifying glasses or magnifying glasses, colposcopes, video cameras, digital cameras, detectors or any image analyzer.

9.- The system can be used with both Graves, Pederson, or other sterilizable or disposable specula.

10.- The electrical cable chosen for the illuminator is hermetically sealed, which allows its sterilization.

11.-This visual technique of selection by speculacopy could be used in the early detection programs of dysplasia of the female genital tract with immediate and good results at the same time that the procedure is performed.

12.- Selective light source in its emission of the fluorescence band that requires only a few minutes for the training of medical and paramedical personnel.

13.- The results of fluorescence speculacopy are evaluated at the same time as the procedure and in the place where it is performed.

14.- The period of uncertainty in the patient is avoided with this procedure since it can be immediately informed of the disease and what treatment will be followed.

15.- It lowers the costs in the handling of the methods and increases the benefit for the population.

Technical description of the invention:

The characteristic details of this new system are clearly shown in the following description and in the accompanying figures, as well as an illustration of it and following the same reference signs to indicate the parts of the figures shown. The invention relates to a combination of a vaginal speculum (Serious or Pederson, etc., sterilizable or disposable) (Figure 1) with an excitation system for fluorescence by means of a high power illuminator (Figure 1-A), with an Emitting Diode of Light (LED) of Nitrogen Gallium (Figure 1-J) with which we can perform the excitation in the diseased cervix and produce the phenomenon of fluorescence by blue light using fluorochrome or Fluorescein Isothiocyanate dye as a marker of HPV-infected tissue Likewise, in order to visualize this image, the speculum contains a "Long Pass Band" barrier filter or a yellow cut (Figures 1-K and 2- D).

In order to fully describe this system, we inform you of the following definitions and basic knowledge to describe the invention.

Light Energy-Light:

The world around us is full of waves, for some of them we can see or hear, but most of these, our senses cannot detect them. In the sub-microscopic world, atoms and molecules are made up of electrons, protons, mesons, photons etc., which move undulatingly forming waves in their bonds. Appropriately stimulated, these atoms and molecules emit waves that we call: gamma rays, x-rays, ultraviolet waves, visible waves, television, radio, infrared radiation, etc. This is known as: Electromagnetic Spectrum.

The waves are described by their amplitude (peak to peak), frequency (Hz) and length (length size) called Lambda (λ).

In the electromagnetic spectrum, light waves are called according to their wavelength, measured in nanometers (nm), billionths of a meter. A nanometer is: 10- ⁹ meters

The visible spectrum, goes from deep red with 700 nm, to violet with 400 nm.

There are different types of light filters, because they let different colors of the spectrum pass, with different wavelengths, there are green, blue, red, anti-thermal etc. but no they are accurate in choosing just one wavelength, since this requires expensive filters, and specially manufactured for specific purposes.

Luminescence (Latin: lumen = light) It is the ability of a body to emit light when it is excited by a source of energy.

Scientifically speaking, luminescence is the optical radiation of a physical system produced during transfer of an excited condition to a basic condition. The light (or photonic energy) emitted is triggered by frequency energy in the x-ray, ultraviolet, infrared or visible spectrum.

The luminescence can be divided into 2 phenomena: phosphorescence and fluorescence. In phosphorescence the body continues to emit light after being excited.

The phenomenon of fluorescence has been observed for thousands of years, this phenomenon has been mentioned in Chinese literature for 3,500 years.

In 1842 Sir George Gabriel Stokes (1819-1903) described the luminescence observed in the mineral calcium fluoride and called it fluorescence.

Fluorescence is the property of certain chemical substances to absorb short waves of light energy and simultaneously produce long wavelengths. Example: Ultraviolet light (short energy) (Figure 3 -A) is absorbed first by the substance and it excites electrons in their orbits (Figures 3-B and 3-C) by passing them to longer orbit spins emitting with this change of light of greater wavelength that affects the visible spectrum (Figure 3 -D), then the electrons return to their site, extinguishing with this the radiation of light of greater wavelength, this law is known as "Law of Stokes-Adams "(Figure 3).

The fluorochrome excitation in our system is described below:

First, fluorochrome is applied by our technique in the cervix, and it is absorbed by the cells of tissues infected by the Human Papillomavirus. The blue light beam emitted by the Light Emitting Diode (LED) affects the fluorochrome inside the cells, and infected tissues. This light energy is absorbed by it in the tissues, and then the fluorochrome itself emits light at different wavelengths of the light with which it was irradiated. The physical phenomenon of fluorescence occurs: The tissue cells fluoresce. The energy of the light irradiated by the Nitrogen Gallium LED at a blue excitation is absorbed by the FITC fluorescein isothiocyanate inside the infected cells exciting their electrons, changing spins and producing the emission of photons. The photon is produced in the change of the electron in its spin, with this physical phenomenon new photons are emitted in a wavelength greater than blue, which is different than the wavelength with which the tissues and cells were originally irradiated.

To be able to see and locate this fluorochrome in the injured cells and tissues a suppressor filter is used: Band Pass Filter "band or cut-off filter" that allows the passage of a yellow and green wavelength, the purpose of these is let frequencies greater than 520 nm pass to be seen, thus infected cells and tissues.

Nowadays Fluorescence is the basis of many modern methods within the Life Sciences that at this time has its greatest objective in molecular and cellular biology, immunology, virology and oncology.

The combination of the vaginal speculum with an excitation system for fluorescence by means of the Light Emitting Diode (LED) of Nitrogen Gallium and the fluorochrome Isothiocyanate Fluorescein (FITC) for the diagnosis of diseases caused by the Human Papillomavirus in the genital tract Feminine is composed of several parts that structure the system:

1.- The vaginal speculum consists of two leaflets or leaves in the form of a "duck's beak" (Figure 1-B) that are insertable in the vagina and that when opened with smooth movements, the vaginal walls can be visualized. The speculum also has a handle (Figure 1-C) with which it allows us to perform the location of the uterine cervix with different movements, positioning the speculum in a way that does not produce a feeling of discomfort in the patient. Once in correct position, this can be fixed with its respective adjustment knob (Figure 1-E), as well as with the leaflet safety (Figure 1-D). The speculum has two entries to remove and put, the one located in the handle allows us to fix the illuminator (Figures 1-F and 4-B) and the second located in the upper leaflet allows us to put the barrier filter holder (Figures 1-G and 2-A).

2.- The illuminator contains the Light Emitting Diode (LED) of Gallium Nitrogen that provides the light to the speculum, this LED is characterized by its brilliance in the light, with hospital-grade electric cable, which allows us to sterilize it.

3.- The illuminator (Figures 1-A and 4- A) consisting of a Light Emitting Diode (LED) of Nitrogen Gallium with a blue spectrum, is placed in the distal part of the illuminator and is located in the speculum ( Figures 1-J and 4-D).

4.- The barrier filter holder (Figures 1-K and 2) is inserted into the posterior lip of the upper leaflet of the speculum by means of a pressure clip (Figures 1-G and 2-A). The filter holder is annular with 2 rings that allow the barrier filter to be accommodated easily (Figure 2-D), the filter is housed between these two rings (Figures 2-B and 2-C).

5.- The illuminator is easily installed in the speculum handle by means of the "U" adapter that is fixed in the speculum handle (Figures 1-1 and 4-B). In the same way as the filter holder, it is inserted into the speculum in the upper leaflet by means of a clamping clip (Figure 4-C).

6.- The Nitrogen Gallium LED is powered by a bipolar electrical cable that comes from a low-voltage direct current source (Figures 1-H and 4-E).

7.- The power supply consists of a battery, it can be rechargeable by an electronic system that allows recharging in 120-220 volts AC lines.

8.- The power switch is located in the electric cable, commonly called passage, which facilitates its maneuverability by the doctor when performing the scan Technique

Speculoscopy method using the vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract:

Clinical Method

We have used Fluorescein Fluorochrome Isothiocyanate (FITC) for various reasons: This is widely used by ophthalmologists, intravenously in fluorangiographies (retina), and in local solution to see corneal lesions, this means no toxicity of part from the dye to the patient.

Procedure: • Comfortably place the patient in a gynecological position. The duration of the study is approximately 10 minutes.

• Introduce the vaginal speculum without lubricants.

• Locate the cervix.

• Apply 5% Acetic Acid on the cervix for one minute. This acidified solution has two functions, it is a bleach of the cells in the

Intraepithelial Cervical Neoplasms (NIC), and is a coupling agent for fluorochrome (FITC) with diseased cells.

• Apply the solution of FITC (fluorescein isothiocyanate) evenly on the cervix for one minute. • Turn on the Light Emitting Diode (LED).

• Insert the suppressor filter. This is the most important step of the results, because the diagnosis is made using this filter, imaging with fluorescent tissue is positive for HPV infection, absence of fluorescent tissue negative for HPV infection, that is, a healthy patient. This is the new diagnostic image of easy interpretation, reason for the patent we are claiming.

The results are obtained at the same time the procedure is performed and in the same place.

Claims

Having sufficiently described the invention we have made, we consider that our invention, which is a New System and Specific Speculacopy Method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract within the Visual Inspection Systems in the World, and that for this reason we are claiming it as an invention of our property is contained in the following clauses:

L- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, characterized by the combination of a standard vaginal speculum: Serious, Pederson etc., sterilizable or disposable with a system to produce fluorescence by means of a specific short band Light Emitting Diode (acronym in English), mounted on the upper part of the illuminator that is located between the 2 leaflets of the speculum, holding it in the handle of the said speculum, with the purpose of emitting a blue ray of light in such a way that the Fluorescein Isothiocyanate (FITC) marker with which the tissue is stained and due to its selective characteristics of the method, only the damaged epithelial tissue in the lesions produced by the human papillomavirus produces phenomenon of fluorescence, and this tissue is observable through a suppressor filter, achieving an accurate diagnosis and At the same time the procedure is being performed, in addition to that a magnifying lens system or a colposcope can be incorporated.

2.- Vaginal speculum with a specific system and method for the diagnosis of lesions produced by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculoscopy system is characterized by the ability to be used with Common vaginal specula such as Graves, Pederson or others of this type, disposable or reusable. That in association with the specific fluorescence method, an accurate diagnosis of the lesions produced by the human papillomavirus is achieved at the same time the procedure is being performed.

3. Vaginal speculum with a specific system and method for the diagnosis of lesions produced by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by using a Diode Emitting Light (acronym in English LED) of Nitrogen Gallium with a short band within the luminous spectrum, which are required for the specific fluorescence system with the fluorescein isothiocyanate marker (FITC), achieving an accurate diagnosis at the same time The procedure is being carried out.

4.- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by the use of an illuminator In the form of the inverted letter "L", its upper and shorter part is introduced in the center of the leaflets, holding the LED, allowing ample illumination of the uterine cervix, in its longer part this is attached to the speculum handle by the adapter "U", inside are the cables that supply the electric current, using the bipolar cable from the battery. The material of the illuminator is sterilizable same as is required by the system, achieving an accurate diagnosis at the same time the procedure is being performed.

5.- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by the use of a filter of cutting or suppression of broadband that allows the passage of only the light produced by Fluorescein Isothiocyanate (FITC) during its excitation, this marker of the tissue injured by the human papillomavirus is excited by the light coming from the Emitting Diode of Light (LED), producing light, this filter suppresses the passage of light produced by the LED and provides a selective image only of the injured tissue allowing it to be identified, giving us an accurate diagnosis of dysplasia at the same time it is being made The procedure.

6.- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by the use of an adapter "U" that allows insertion by means of a clip of the illuminator to the handle of the speculum, achieving an accurate diagnosis at the same time the procedure is being carried out.

7.- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by a clip that allows fixing the barrier filter holder to the outer part of the upper leaflet of the speculum and in the same way allows us to introduce the barrier filter in the visual field so that it can identify the lesion providing us with an accurate diagnosis at the same time the procedure is being carried out .

8.- Vaginal speculum with a specific system and method for the diagnosis of lesions produced by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by a barrier filter holder, same consisting of two rings that are held by a thread themselves that allow the barrier filter to be accommodated, through this thread to remove, put and turn the filter, it is easily inserted in order to provide an accurate diagnosis at the same time in that the procedure is being carried out.

9.- Vaginal speculum with a specific system and method for the diagnosis of lesions caused by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by a rechargeable battery through a 110-220 Volt power converter in order to provide an accurate diagnosis at the same time that the procedure is being performed even in the most distant places of the population.

10.- Vaginal speculum with a specific system and method for the diagnosis of lesions produced by the Human Papillomavirus in the female genital tract, according to clause 1, the new diagnostic speculacopy system is characterized by a sealed electrical cable that It provides the electric power to the hospital-grade LED that allows its sterilization in order to provide an accurate diagnosis at the same time the procedure is being performed.