BR112019011766B1 - BRUSH BIOPSY DEVICE, KIT AND METHOD - Google Patents

Abstract

Biopsy device comprising a flexible coaxial structure comprising an obturator within a housing, the obturator being adapted to be displaced relative to the housing along the coaxial axis by a force applied to a proximal end; a disruptor, at a distal end of the obturator, adapted to disrupt a tissue surface to release cells therefrom, having a first covered position within the housing and a second position freely extending beyond the housing; an element, having a fixed position in the shell, configured to limit a depth of insertion of the shell into the uterine cervix.

Description

FIELD OF INVENTION

[001] The present invention provides a system and a method for performing a biopsy of the uterus. More particularly, it is a device that disrupts and samples endometrial cells and, at the same time, removes a sample with an abrasive brush and an aspirate.

BASICS OF THE INVENTION

[002] The present technology represents improvements over US patents Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856, each of which is incorporated herein by reference in its entirety. These patents, in turn, represent an improvement over the L.U.M.C Cook Medical Tao Brush™ Endometrial Sampler, and the Pipelle endometrial biopsy device (See, Sierecki AR, Gudipudi DK, Montemarano N, Del Priore G., “Comparison of endometrial aspiration biopsy techniques: specimen adequacy.” J Reprod Med. 53 (10): 760-4, October 2008), expressly incorporated herein by reference.

[003] As shown in Figs. 1A and 1B, the Tao BrushÔ has a sphere at the tip, to reduce trauma when the brush reaches the bottom of the uterus. Figure 1A shows the brush extended from the housing, while Figure 1B shows the brush retracted. Next to the brush, on the guide wire, is an internal housing provided to center the wire, but this does not provide an interference fit and does not remove a vacuum when the guide wire is retracted. The sample obtained by the Tao Brush™ represents the cells swept or abraded from the endometrium by the bristles. See also, 4,227,537; 3,877,464; 9,078,642; 5,916,175; 5,954,670; 6,059,735; 6,610,005; 7,767,448; 8,827,923; 8,439,847; 8,251,918; 7,749,173; 5,546,265; 3,881,464; 4,108,162; 8,968,213; 8,323,211; D658,388; 5,713,369; 5,546,265; 4,235,244; 4,754,764; 4,763,670; 4,966,162; 5,146,928; 5,253,652; 4,662,381; 5,217,024; 5,279,307; 6,336,905; each of which is expressly incorporated herein by reference in its entirety.

[004] Figs. 2A and 2B show a Tao BrushÔ, with the handle at the opposite end of the brush visible.

[005] Figs. 3A-3D show the use of the Tao BrushÔ. The manufacturer (Cook Medical) provides the following instructions for use: 1. Position the screw cap test tube containing 8 ml of CytoRich® Brush Cytology Preservative (AutoCyte, Inc., Elon College, NC) in a holder for test tubes at the procedure site. 2. Place the patient in the lithotomy position. 3. Completely retract the brush sampler into the outer casing. (Figure 2) 4. Carefully insert the device at the level of the fundus of the uterus. (Figure 3A) 5. Pull the outer casing back to the cable. Rotate the brush sampler widely. (Figure 3B)

[006] Two methods are suggested: 1) Rotate the brush sampler clockwise until the reference mark on the handle indicates completion of a 360° turn, then rotate counterclockwise (opposite direction) until the reference mark on the cable indicates completion of a 360° turn; 2) Rotate the brush sampler in only one direction, completing 4 or 5 360° rotations. NOTE: The reference mark on the handle indicates completion of a 360° rotation. 6. In order to capture the endometrial material in situ, push the outer casing in relation to the brush to the tip and remove the device. (Figure 3C). The normal endometrial cavity is in a collapsed state, therefore the brush will have direct contact with the entire endometrial surface. 7. Immediately immerse the device in 8 ml of CytoRich® Brush Cytology Preservative. 8. Retract the housing to expose the brush to a preservative solution. 9. Hold the wrapper firmly and move the brush in and out of the wrapper to clean it of adherent cells and tissue. (Figure 3C) NOTE: Collections are preservative stable for periods of up to several weeks. 10. Remove the brush assembly from the test tube, replace the screw cap, and send the tube to the laboratory for processing.

[007] To Obtain Uncontaminated Endometrial Cultures 1. After inserting a sterile, non-lubricated vaginal speculum, use the swab on the ectocervix and endocervical canal with povidone-iodine solution. NOTE: Insert the swab approximately 1.5 cm into the endocervical canal to ensure use of the endocervical swab with povidone. 2. Insert the brush into the endometrial cavity following steps 3-6 in the section preceding these instructions. The reference mark on the handle indicates completion of a 360° turn. 3. Remove the sampler. 4. Clean the rounded tip of the brush with a gauze pad containing 95% alcohol. 5. Pull the casing back. Prepare for morphological assessment (if necessary), to prepare a direct smear on a sterile glass slide and spray fix immediately. 6. For culture studies, place the brush in sterile Stuarts transport medium and shake for 5 seconds.

[008] Figs. 4A and 4B show a Pipelle biopsy tool, which aspirates a sample into a housing, as shown in Figs. 5A-5C, but does not have an exposed brush.

[009] Figs. 6-7 show the design in accordance with US Patent Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856, expressly incorporated herein by reference, which improve on the Tao BrushÔ design by implementing an aspiration biopsy in addition of an abrasive tissue sampling biopsy. This is accomplished by providing an interference fit plunger near the biopsy brush, which withdraws a sample of fluid from the uterus as the brush is withdrawn into the sheath.

[0010] However, in accordance with the Tao BrushÔ design and US patents Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856, the brush is inserted at an arbitrary or estimated distance, or even resistance is met by the tip of the brush pushing against the fundus of the uterus, which can cause unnecessary tissue damage and, in some cases, complications.

[0011] US Patent Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856 discuss an intrauterine biopsy sampling device having a narrow cylindrical tube with a guidewire and biopsy sampling device at the end of the guidewire, similar to an I.U.M.C. endometrial sampler. Tao BrushÔ from Cook Medical (Bloomington, IN), modified so that arranged within the housing, is a piston-type structure which, when the wire is withdrawn through the housing, draws a vacuum and sucks the fluid surrounding the guide wire to the casing. A vacuum biopsy sampling device, such as the well-known Pipelle endometrial suction curette, produces a vacuum and draws it into the housing by a similar principle, but does not have the brush or other biopsy sampling device at its distal end.

[0012] The device has a coaxial “straw” 1 to 3 mm in diameter by 30 to 40 cm in length 1 that can easily pass into the endometrial cavity of the uterus with little or no discomfort. It is malleable but rigid enough to apply enough force to pass through the cervix. In the center of the outer shell, which is a waterproof tube, a thinner inner insert 2 can be extended beyond the end of the tube 3 into the uterus. Next to the biopsy brush is a suction element 4, which draws liquid into the housing when the guide wire is removed. The obturator internus ruptures the uterus to loosen and collect a biopsy sample from the uterus. The tissue sampling device includes a spirally twisted flexible wire with opposing proximal and distal ends. Also included is a plastic tube covering a significant portion of the wire to provide additional rigidity without making the overall brush rigid.

[0013] Along the distal end portion of the wire is a brush that includes bristles that were used to collect a tissue sample. The bristles are fixed within the spirally twisted wire near the distal end and are tapered from smaller to larger towards the distal end of the wire. The tapering of the bristles from the distal end of the device allows for more global tissue collection of the endometrium due to the shape of the endometrial cavity. An atraumatic bulb is located at the extreme distal end of the twisted wire. The plastic tube and twisted wire are contained within a housing of shorter length than the twisted wire, so that the housing can be moved along the plastic tube to the atraumatic bulb at the distal end of the twisted wire, thus covering the brush. during brush insertion and removal after tissue collection.

[0014] Prior to insertion, the casing can be moved into position by the distal end of the twisted wire to protect the brush during insertion. Having the brush covered during insertion also increases comfort for the patient and protects the brush from collecting tissue from unintended areas. The housing is moved back to the proximal end of the stranded wire after the device has been inserted to the appropriate collection depth, exposing the brush and allowing a tissue sample to be collected. The wrapper can be moved to completely uncover the brush, or it can be moved in gradients to uncover portions of the brush. This allows the doctor to adjust the effective brush collection area based on the patient's anatomy.

[0015] The plastic tube covering the thread is marked in centimeter gradations along the plastic tube with markings indicating the exact length of the brush inserted into the uterus, starting from the distal tip of the brush to the proximal end of the plastic tube. This lets the clinician know how deep the brush is inserted into the uterus. The casing is approximately the same length as the plastic tube and in position to cover the brush bristles before insertion. The casing may be formed from a translucent material so that gradations in the plastic tube can be seen through the casing. The ability to measure insertion depth increases certainty that the tissue sample collected is from the correct area. After a tissue sample is collected from the appropriate area, while the tissue sampling device remains inserted, the housing can be moved back along the distal end of the twisted wire to cover the brush bristles before removing the brush. This allows the tissue sample to be protected on the brush inside the housing during removal.

[0016] Additionally, gradations along the flexible tube allow the doctor to measure the length of the exposed bristles. As the practitioner pulls the wrapper from its insertion position toward the handle, the more the wrapper is pulled, the more bristles are exposed. Gradations (ruler) provide visual confirmation of this measurement and allow the practitioner to be accurate by exposing only a certain length of brush bristles. This measurement allows the clinician to have better control of where tissue is sampled and allows the clinician to adjust the length of the brush based on patient-specific parameters; such as uterine size measured during previous tests or inferred based on patient history. Brush exposure control increases sampling accuracy and patient comfort.

[0017] Simultaneously with withdrawing the inner obturator back into the narrow cylindrical tube, the device creates a weak suction to collect the ruptured sample into the outer tube. The entire device is then removed from the uterus and the sample is collected by reversing the process outside the body.

[0018] Combining two or more biopsy methods in one device eliminates the pain, discomfort and inconvenience of, for example, a second procedure to obtain an adequate and accurate sample. Multiple sample collection methods, e.g., physical rupture and suction, used together, allow for a gentler application of the individual methods; for example, a soft rupture and gentle suction applied simultaneously can replace a forceful rupture, for example D&C, and powerful suction. Combining multiple gentler methods in one device is safer and more effective than any one method alone.

[0019] See (each of which is expressly incorporated herein by reference in its entirety): Yang GC, Wan LS, Del Priore G. Factors influencing the detection of uterine cancer by suction curettage and endometrial brushing. J Reprod Med 2002; 47:1005-10. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted on the SEER web site, 2007. McCluggage WG. My approach to the interpretation of endometrial biopsies and curettings. J Clin Pathol. 2006;59:801-12. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of the patients with endometrial carcinoma and hyperplasia: a meta—analysis. Cancer 2000; 89(8):1765-72. Feldman S, Berkowitz RS, Tosteson AN. Costeffectiveness of strategies to evaluate postmenopausal bleeding. Obstet Gynecol 1993; 81(6):968-75. Grimes DA. Diagnostic dilation and curettage: A reappraisal. Am J Obstet Gynecol 1982; 142:1-6. Ong S, Duffy T, Lenehan P, Murphy J. Endometrial pipelle biopsy compared to conventional dilatation and curettage. Go J Med Sci 1997; 166:47-9. Tahir MM, Bigrigg MA, Browning JJ, Brookes ST, Smith PA. A randomized controlled trial comparing transvaginal ultrasound, outpatient hysteroscopy and endometrial biopsy with inpatient hysteroscopy and curettage. Br J Obstet Gynecol 1999; 106(12):1259-64. Ferry J, Farnsworth A, Webster M, Wren B. The efficacy of the pipelle endometrial biopsy in detecting endometrial carcinoma. Aust N Z J Obstet Gynecol 1993; 33:1-76. Guido RS, Kanbour-Shakir A, Rulin M, Christopherson WA. Pipelle endometrial sampling: sensitivity in the detection of endometrial cancer. J Reprod Med 1995; 40:5535. Stovall TG, Photopulos GJ, Poston WM, Ling FW, Sandles LG. Pipelle endometrial sampling in patients with known endometrial carcinoma. Obstet Gynecol 1991; 77:954-6. Van den Bosch T, Vandendael A, Wranz PA, Lombard CJ. Endopap-versus Pipelle-sampling in the diagnosis of postmenopausal endometrial disease. Eur J Obstet Gynecol Reprod Biol 1996; 64:91-4. Huang GS, Gebb JS, Einstein MH, et al. Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. Am J Obstet Gynecol 2007; 196:243.e1-243.e5. Kozuka T. Patch testing to exclude allergic contact dermatitis caused by povidone-iodine. Dermatology 2002; 204 Suppl 1:96-8. Borja JM, Galindo PA, Gomez E, Feo F. Contact dermatitis due to povidone-iodine: allergic or irritant?. J Investig Allergol Clin Immunol 2003; 13(2):131-2. Naim NM, Mahdy ZA, Ahmad S, Razi ZRM. The Vabra aspirator versus the pipelle device for outpatient endometrial sampling. Aust N Z J Obstet Gynecol 2007; 47(2):132-6. Phillips V, McCluggage WG. Results of a questionnaire regarding criteria for adequacy of endometrial biopsies. J Clin Pathol. 2005; 58:417-9.

SUMMARY OF THE INVENTION

[0020] A preferred embodiment of the present invention provides a narrow cylindrical tube with a biopsy sampling device and guide wire at the end, similar to an I.U.M.C. Endometrial Sampler. Tao Brush™ from Cook Medical (Bloomington, IN)., modified so that around the cylindrical tube, a cervical stop is provided that limits insertion of the tube to a fixed distance beyond the external os of the uterus.

[0021] This feature can be combined with a suction device to withdraw a liquid sample into the lumen of the narrow cylindrical tube, in accordance with US patents Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856.

[0022] The device is intended to collect tissue samples from the inner lining of the uterus (endometrium). The device has a brush at the distal end of the catheter. The brush is intended to gently sample the endometrium. The proximal end of the device has a handle to facilitate physician manipulation. The device has a relatively rigid outer casing, which can move along the length of the device (relative to the handle) to cover or expose the brush at the distal end.

[0023] The device has a skirt-type plug around the distal end of the outer casing. The skirt is intended to locate the device relative to the cervix, and can be secured in position or manually slid along the outer casing (with a tight enough fit to remain axially fixed in position after placement, so that when touching the cervix, manipulation of the guide wire and sheath will not reposition the skirt plug). A series of axial markings are preferably provided to permit quantitative alignment of the skirt plug along the housing. The skirt type tampon is preferably made of an elastomer with rounded edges, such as rubber, silicone or plastic, having sufficient elasticity to provide the desired characteristics and avoid unintentional traumatic injuries.

[0024] The device is intended to be advanced into the patient with the brush covered by the outer casing until the skirt meets the cervix and cannot advance further. After the skirt is tamponed against the cervix, the brush is advanced past the end of the sheath, moving the guidewire relative to the sheath, to expose the brush within the uterus to allow tissue sampling.

[0025] The device also has an O-ring attached to the main shaft of the catheter. The outer housing and O-ring create a seal against each other, and create suction (vacuum) at the distal end of the catheter to trap tissue samples when the guidewire and brush are withdrawn into the housing.

[0026] The device is removed from the patient with the brush covered by the outer casing. An atraumatic bulb may be provided at the end of the brush, which may seal against the distal end of the housing when the guide wire is withdrawn into the housing. A stop may be provided to limit withdrawal of the guide wire in the casing. For example, a toroidal or cylindrical member affixed in a fixed position within the housing may interfere with the Oring and thus limit retraction.

[0027] The device is preferably sterile and intended for single use only.

[0028] According to another embodiment of the invention, a multiple sample biopsy device is provided, capable of obtaining and segregating a plurality of biopsy samples taken in a single session. According to this embodiment, the biopsy instrument is placed in an anatomical orifice, such as a cervical orifice or anus. Advantageously, a protuberance provides a positional reference with respect to the outer portion of the orifice, similar to the skirt mentioned above. This protuberance may be part of the design, or an element added to achieve the desired insertion depth reference function.

[0029] The biopsy device according to this embodiment provides a plurality of biopsy sampling tools, which may be the same or different, for example, an endocervical sampler, an endometrial sampler, a puncture sampler and a suction endometrial sampler. . Each tool is provided as a device within a housing, such as a 1.5-4 mm tube, which is operable by a guide wire to extend the sampling head of the tool beyond the end of the housing, rotate relative to the housing, and retract the sampling head of the tool back into the housing.

[0030] In addition to providing control over the advancement of the biopsy tool relative to the housing, each housing is controllable to be selectively inserted into the orifice and advanced into the organ with the biopsy tool retracted in the housing and to be removed from the organ with the biopsy tool has retracted into the housing.

[0031] In some cases, the casing itself may be pivotable or angularly orientable to direct the biopsy tool to a desired region. The pivotable housing may be a single axis, that is, a curvature of the end of the housing, typically as a result of a pull on a traction element such as a cable, guide wire or filament affixed to the wall of the housing. By controlling the angle of curvature, and the angle of rotation of the casing relative to the organ, a reasonable range of control is provided.

[0032] Similarly, a punch or loop or encapsulation biopsy device can also be controlled by a pull, which can be a thread or polymer filament. Thus, the case of a single guidewire with a single degree of freedom (advance/retraction) is a simpler case, and additional controls and degrees of freedom can be provided.

[0033] In some cases, “blind” sampling can be carried out, for example, within a short canal, or in a distal portion of the organ in relation to the orifice.

[0034] In other cases, for example, within a lumen of a larger organ, some imaging orientation is preferred. Therefore, the device can be used with an endoscope and/or include an endoscopic camera, such as a 1-3mm endoscopic camera. Typically, these devices rely on optical fiber from the tip to the imager for illumination and imaging. However, according to one embodiment of the technology, the imager circuit and lens are present at the tip of the oscilloscope, which in turn is disposed near the end of the biopsy sampling device, to provide direct and efficient imaging. in real time of the biopsy procedure.

[0035] For example, On Semiconductor provides several suitable devices, such as the MT9V115 1/13" VGA imager, OV6922 1/18" M VGA imager, and OVM6946 1/18" 400x400 imager, which can be included as part of a subminiature module that transmits the image as a data stream over an electrical (or wireless) interconnect. The imager is typically provided with a field of view facing the biopsy tool, with an array of LEDs, or LED-illuminated fibers, illuminating the field. Although the chamber is not required in all modes of operation, that is, all sampling procedures, if provided, can remain inserted into the orifice throughout the procedure. The camera may be present near the end of the casing and advanced with the respective biopsy tool casing into the organ during the procedure.

[0036] Advantageously, the video signal from the imager can be transported using the guide wire(s) controlling the biopsy tool as electrical power and/or signal carriers. Note that the operating voltage is typically low, e.g. <3.3V, therefore a dangerous condition for the patient would not be present in the event of an electrical leak. However, power-carrying members can be isolated to further reduce risk and enhance signal integrity. Wireless transmission can also be provided, for example, to a nearby wireless receiver, avoiding the need for wired transmission. In this case, the device may have an independent battery, or receive operating power over a conductor, which may advantageously include the guide wire. Since the preferred guide wire is multi-stranded, power and ground, as well as signal, can be transmitted if the strands are mutually insulated. There is no compelling reason why a guide wire needs to be deflated, which allows for increased use of an existing structure with low added cost and complexity.

[0037] The biopsy device according to this embodiment provides a cylindrical cartridge with the various biopsy tools in angularly offset positions. One was to selectively activate certain tools to provide the barrel with a single active position, in which the user-controlled manipulator provides functional control over a single tip of the plurality of biopsy tips, e.g., extension and retraction of the housing and extension, retraction and guide wire rotation. As discussed above, a function for articulating the housing by pulling on another actuation filament can also be provided. The remaining biopsy tools in the drum can remain retained in their retracted positions, e.g. locked in position.

[0038] Because the barrel has a larger diameter than the casing, the barrel is held outside the bore, and a mechanism for engaging and disengaging each respective biopsy tool is also outside the bore, which, for example, can rotate to the position to release one tool while locking the others in the retracted position. Thus, a relatively large drum, e.g. 8-20 mm, can be provided with 2-12 biopsy tools in reserve. The end of the drum mechanism advantageously serves as the skirt, to limit the insertion distance of the casing to the organ, and provide a well-defined positional reference.

[0039] According to one embodiment, each biopsy tool in the device is separate, without any change in control. Thus, for a biopsy device with four implantable biopsy tools, there are four separate casings with corresponding guide wires extending from the cartridge. This allows a doctor to select the appropriate biopsy tools for a respective procedure from generic or custom designs. Unused tools remain outside the organ while an active tool is in use. In some cases, multiple tools may be advanced to the organ, for example, when an endoscope is provided as one of the available tools, and not linked to a specific or single biopsy tool.

[0040] On the other hand, in a second embodiment, a mechanism may be provided to separately mechanically engage the casing, guide wire and pivot wire for each separate biopsy tool, with a single control system extending from the cartridge. For example, a multi-way clamp, bayonet socket, quick release mechanism or magnet may be provided to individually engage the respective biopsy tool in the active position. The cartridge is typically round, and centered in the orifice during the procedure, so that non-implanted biopsy devices are eccentric within the cartridge when not in use. As they are brought into the active position, for example by rotating a clamping/locking control, and centering the controls for that respective biopsy tool they are also connected and activated. The camera can also be attached to the active biopsy tool at this time. Alternatively, the camera is inserted before the biopsy tool, and is positioned separately from the biopsy tools.

[0041] In some cases, an electrical mechanism may be provided in the cartridge, for example, to latch lock the mechanical controls, to extend the housing to a desired insertion depth, to rotate the brush and retract the housing and/or the biopsy brush in the housing. Typically, biopsy brush extension and axial manipulation are user-controlled rather than automated, although a fully automated biopsy is possible.

[0042] It is preferred that each biopsy tool has a mechanical limiter to control and restrict movements within a predetermined range, wherein the predetermined range may differ for the various biopsy tools depending on their intended application use. Advantageously, the axial control limits are referenced to the outer surface surrounding the insertion hole, and to the end of the barrel, a ring or protuberance surrounding the barrel used to maintain this position reference without slipping into the hole.

[0043] For example, the endocervical brush will typically have the housing extending 0-2 cm beyond the orifice, and an endometrial brush will typically have the housing extending 2-10 cm past the cervix, into the uterus, and a Brush biopsy will extend 1-3 cm beyond the end of the shell. Endocervical and endometrial brushes may be provided with or without suction, which may be provided by the mechanical action of a plunger as the guide wire controlling the brush is withdrawn into the housing, or by a vacuum provided through the cartridge housing or in addition.

[0044] A punch or cup biopsy tool is typically used under visual observation with the video imager, and may be less mechanically constrained in this circumstance, as the user is assumed to have control over the device during use. .

[0045] Therefore, the present design allows multiple biopsies to be performed in a single session, from different regions of the organ, and kept segregated from each other. From the patient's perspective, this is advantageous because the sampling procedure is facilitated, and the combined time and economic expenditure will typically be less than if separate biopsy tools are employed. Furthermore, compatibility with a single imager used for a plurality of biopsy procedures is also efficient. Finally, in the case of a cartridge that disconnects from a standard cable, the cartridge provides an efficient way to arrange and label samples from a single patient, and makes pathological examination of multiple samples from the same patient and the same organ more efficient. Finally, because each sample is precisely labeled with depth relative to the orifice, clinically important information is obtained, compared to traditional biopsy tools that do not provide an accurate depth reference. Note that a memory card, such as a micro-SD card, may be associated with the cartridge, which includes video and/or manipulation history information for each biopsy tool, which is automatically recorded and maintained, and which may be easily passed on to the pathologist or be part of the patient's medical record.

[0046] Therefore, it is an object to provide a tissue sampling device, comprising: a flexible housing having at least one distal portion configured to maintain an internal vacuum; a skirt plug configured to maintain the sheath at a fixed insertion depth through the cervix within the uterus; and a displaceable structure within the housing to form a coaxial structure; the displaceable structure having a first end extending from a proximal end of the housing and a second end configured to, in a first state, extend from a distal end of the housing, and in a second state, be retracted toward the distal end of the housing. casing; the second end of the displaceable structure having a cellular sampling structure, preceded by a suction element; and the coaxial structure being configured such that a pull on the first end of the displaceable structure at the proximal end of the housing results in a retraction of the displaceable structure from the first state to the second state, to generate suction to cause a displacement of means external to the housing in the casing distal to the piston.

[0047] The displaceable structure may terminate at the second end in an atraumatic bulb.

[0048] The cellular sampling structure may comprise a brush.

[0049] The brush may comprise a plurality of bristles extending radially from the displaceable structure. The brush may have a cross section that tapers relative to the distance from the second end. The brush may have a helical cross-section profile.

[0050] The coaxial structure can be configured for insertion at a predetermined depth into the cervical os of a human uterus, to retrieve an endometrial biopsy sample, and to be withdrawn from the cervical os of the uterus.

[0051] The coaxial structure can further be configured to be: inserted into the cervical orifice with the structure displaceable in the second state to a predetermined depth; extended in the first state with the cell sampling structure inside the uterus; manipulated by a user by moving the first end of the displaceable structure to dislodge cells within the uterus; retracted to the second state within the uterus to cause the vacuum to draw a liquid sample surrounding the cell sampling structure to the distal end of the shell; and retracted from the cervical os with the displaceable structure in the second state.

[0052] The displaceable structure may comprise a flexible guide wire twisted into a spiral.

[0053] The casing can have an outer diameter between 1 and 3 mm and a length between 20 and 50 cm.

[0054] It is also an object to provide a mode of tissue sampling, comprising: providing a coaxial structure, comprising a flexible casing having at least one distal portion configured to maintain an internal vacuum, a skirt around the flexible casing, configured to limit a depth of insertion of the flexible shell into a human cervix; and a displaceable structure within the housing to form a coaxial structure, the displaceable structure having a first end extending from a proximal end of the housing and a second end configured to, in a first state, extend from a distal end. of the casing, and in a second state, to be retracted to the distal end of the casing, and the second end of the displaceable structure having a cellular sampling structure, preceded by a piston; and applying a pull to the first end of the displaceable structure at the proximal end of the casing to retract the displaceable structure case from the first state to the second state, generating the vacuum.

[0055] The coaxial structure can be configured for insertion into the cervical os of a human uterus to the predetermined insertion depth, to retrieve an endometrial biopsy sample, and to be withdrawn from the cervical os of the uterus.

[0056] The method may further comprise: inserting the distal portion of the coaxial structure into the cervical orifice of a uterus, with the structure displaceable in the second state to the predetermined depth; extending the distal portion of the coaxial structure to the first state with the cell sampling structure within the uterus; manipulating the first end of the displaceable structure to dislodge the cells within the uterus; retracting the coaxial structure in the second state within the uterus, causing the vacuum to draw a liquid sample surrounding the cellular sampling structure to the distal end of the casing; and retracting the distal portion of the coaxial structure from the cervical orifice with the displaceable structure in the second state.

[0057] The cell sampling structure may comprise a brush having a plurality of bristles extending radially from the displaceable structure and terminating in an atraumatic bulb.

[0058] The displaceable structure may comprise a spirally twisted flexible guide wire, further comprising twisting the guide wire to rotate the cellular sampling structure.

[0059] It is yet another object to provide a flexible coaxial biopsy device, comprising: a tubular casing having a wall configured to maintain an internal vacuum relative to an exterior of the tubular casing; a flanged member on an outer surface of the tubular casing, configured to limit an insertion depth of the tubular casing into a cervix; a displaceable wire within the tubular casing; and a cell sampling device configured to rupture a surface of a tissue, mounted on the displaceable structure distal to the element, configured to project from a distal end of the tubular casing when the displaceable element is disposed in a first state, and to be contained within of the distal end of the tubular casing when the displaceable element is arranged in a second state.

[0060] The cell sampling device may comprise a plurality of bristles extending outwardly from the displaceable wire, terminating at the distal end in an atraumatic bulb.

[0061] The device may be configured to insert into the cervical os of a human uterus to the predetermined depth, to retrieve an endometrial biopsy sample from within the uterus, and to be withdrawn from the cervical os of the uterus after the endometrial biopsy is obtained.

[0062] The device can further be configured to be: inserted into the cervical os with the wire displaceable in the second state to the predetermined depth; extended in the first state with the cell sampling device inside the uterus; manipulated by moving the first end of the displaceable wire to dislodge the endometrial cells; retracted to the second state within the uterus, to extract the vacuum to withdraw a liquid sample surrounding the cell sampling device to the distal end of the tubular casing; and retracted from the cervical os with the displaceable wire in the second state.

[0063] The device may further comprise an element that creates a negative pressure within the tubular casing when the displaceable wire is withdrawn into the tubular casing.

[0064] The biopsy brush described above can also be revised for use as an anal biopsy brush, and an endometrial biopsy brush and an anal biopsy brush can be provided together as a kit, optionally alone with a bottle of preservative solution ( for a single brush), or a plurality of preservative bottles for a kit. The kit is preferably a sterile, double-wrap package containing the biopsy brush or brushes, a bottle or bottles of preservative, and optionally a lubricant acceptable for cytological sampling, and optionally a sterile sheet or drape. disposable.

[0065] The anal biopsy brush differs from an intrauterine biopsy brush in that it will be shorter, since the working distance between the doctor or caregiver and the patient's orifice is shorter. For intrauterine use, the sheath is typically 20-25 cm long, with a 4 cm long brush and 2 cm of guide wire exposed, so that the wire is 26-31 cm long beyond the end of the cable to which it is attached, with a skirt on the casing about 4 cm from the distal end.

[0066] An anal biopsy brush housing will typically be 8-12 cm long, with the skirt approximately 4 cm from the distal end. For example, an anal biopsy brush may have an 8 cm long housing with the skirt located 4 cm from the distal end, having a 14 to 18 cm long guide wire for sampling in the rectum up to 6 cm after the tip of the anal biopsy brush. casing.

[0067] A kit may therefore include a long intrauterine biopsy device having a sheath length of about 20 cm, a short anal biopsy device having a sheath length of about 8 cm, two vials of cytological preservative, a package of cytologically acceptable water-based lubricant (e.g., surgilube®, which preferably does not include carbomers), a sterile drape, package insert labeling instructions (which may be printed on the package, as appropriate). Any lubricant should be applied to the outside of the housing, between the skirt or flange and the distal tip, with the brush in the retracted position, taking care to avoid lubricating the housing or brush end.

BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Figs. 1A, 1B, 2A and 2B, show a Tao Brush of the prior art in the extended and retracted states in relation to the casing, respectively, the internal obturator and breaker elements, which can be, for example, a brush, conical helical screw, loop or loop with brush elements or similar.

[0069] Figs. 3A-3D show illustrations of using the Tao BrushÔ.

[0070] Figs. 4A and 4B show a prior art Pipelle endometrial biopsy device in the extended and retracted states, respectively.

[0071] Figs. 5A-5C show the use of the Pipelle device in a biopsy procedure.

[0072] Figs. 6 and 7 show an improved endometrial biopsy brush with suction in accordance with US Patent Nos. 9,351,712, 8,920,336, 8,517,956 and 8,348,856.

[0073] Fig. 8 shows a guide wire and a biopsy brush according to the present invention.

[0074] Fig. 9 shows a skirt-type plug according to the present invention.

[0075] Fig. 10 shows a narrow housing with a skirt-type plug installed in accordance with the present invention.

[0076] Fig. 11 shows a biopsy device complete with handle, skirt plug, casing, guide wire, brush and O-ring, in accordance with the present invention.

[0077] Fig. 12 shows an arrangement of an independently controllable multi-sample biopsy device, which shows four different biopsy sampling tools.

[0078] Fig. 13 shows an arrangement of an independently controllable multi-sample biopsy device, which shows four different biopsy sampling tools.

[0079] Fig. 14 shows a detail of a selector that allows the manipulation of a single biopsy sampling tool in a cylindrical cartridge.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Example 1

[0080] A preferred embodiment of the present invention consists of an intrauterine biopsy device having a thin-walled outer tube of approximately 2.25 mm in outer diameter and 1.2 mm in inner diameter; the length is between 20-50 cm, for example 22 cm. This tube may be a translucent, collapsible but independent plastic tube made, for example, of nylon. The guide wire is preferably a twisted stainless steel wire of approximately 0.1-0.2 mm in diameter, having sufficient mechanical properties to transmit the forces for extension and retraction of the brush during use. At the distal end of the guide wire is a biopsy brush, shown in Figs. 8 and 11, with an atraumatic bulb at the tip. The brush can be about 4 cm long and extends about 2 cm beyond the end of the casing when extended. The O-ring preferably remains inside the casing throughout the entire travel range, to avoid problems in re-engaging the end of the casing. For example, the O-ring (or, more fully, the plunger affixed to the wire) may be, for example, 2-5 mm from the end of the casing when extended.

[0081] An anal biopsy device may also be provided, having a thin-walled outer tube of approximately 2.25 mm in outer diameter and 1.2 mm in inner diameter; length is between 8-12, for example 8 cm. This tube may be a translucent, collapsible but independent plastic tube made, for example, of nylon. The guide wire is preferably a twisted stainless steel wire of approximately 0.1-0.2 mm in diameter, having sufficient mechanical properties to transmit the forces for extension and retraction of the brush during use. At the distal end of the guide wire is a biopsy brush, shown in Figs. 8 and 11, with an atraumatic bulb at the tip. The brush for the anal biopsy device may also be 4 cm long, with the O-ring or piston 2-5 mm from the end of the housing when the brush is extended.

[0082] The wire may be marked periodically, such as in 1 cm increments, so that the physician or biopsy device operator can estimate the insertion of the brush in relation to the proximal end of the casing.

[0083] At one end, the one that enters the uterus or anus, the biopsy brush is formed. A tight-fitting O-ring around the guide wire, shown in Fig. 11, acts as a piston and creates suction when the obturator is withdrawn through the thin-walled outer tube.

[0084] In another embodiment, the O-ring may be arranged about 2.5 cm from the tip, with the brush extending about 1.5 cm from the tip, with 1 cm of uncapped wire between them. .

[0085] As shown in Figs. 9, 10 and 11, a skirt-type plug is provided around the exterior of the thin-walled tube, near the distal end, which may be in a fixed position or manually slidable. The skirt is approximately 1 cm in diameter, and may be formed from nylon, polyurethane, silicone, neoprene, or other medically acceptable plastic or rubber. Typically, the skirt is fixed in position, and may be glued (e.g., UV-activated methyl methacrylate adhesive) or molded into the housing in position.

[0086] The biopsy device is used as follows:

[0087] The brush is completely retracted into the outer casing.

[0088] The sheath is inserted, through the vagina, into the cervix, until the skirt-type plug reaches the external orifice of the cervix. The tip of the brush must be moved away from the bottom of the uterus.

[0089] The outer casing is pulled back until it stops, that is, it touches the cable. The brush is then rotated by holding the casing still and turning the handle. For example, the brush can be rotated clockwise until a reference mark on the handle indicates completion of a 360° turn, and then rotated counterclockwise until the reference mark on the handle indicates completion of a full 360° turn. -360° turn. Alternatively, the brush can be rotated in just one direction, completing 4 or 5 360° rotations. In some cases, the brush can be repositioned axially, although it should not be removed from the housing until sampling is completed.

[0090] After sampling with the brush, the guide wire is pulled on the handle, until the casing reaches the stop (for example, the edge of the handle), thus suctioning the fluid surrounding the tip into the casing and then removing the brush to the casing.

[0091] After removing the device from the vagina, the brush and fluids in the housing are immersed in a cytology preservative, such as formalin, and the sample is washed from the brush into the preservative by moving the brush in and out of the casing immersed in the fluid.

[0092] The invention can be used, for example, to sample the inside of the uterus to diagnose abnormalities. It can detect or exclude cancer. You can obtain an adequate tissue sample to determine the causes of infertility.

[0093] The anal brush is similarly used. This biopsy tool typically has a shorter housing and guidewire than an endocervical brush biopsy tool due to easier anatomical access. For example, the casing may be 10-15 cm long, and the brush may extend 2-6 cm beyond the end of the casing. As with the endocervical brush biopsy tool described above, a skirt is preferably provided, which prevents insertion of the casing into the anus beyond the casing, to provide a physical reference distance for insertion. In some cases, the skirt may be repositioned in the housing to allow the clinician the ability to determine at what insertion depth the sample should be acquired. Advantageously, readjustment requires more force than would be possible by applying unrestricted compression of the housing against the skirt plug so that the position is maintained during use, but the frictional force can be overcome when the biopsy tool is external to the body.

Example 2

[0094] According to a second embodiment, a multiple sample biopsy device is provided, capable of obtaining and segregating a plurality of biopsy samples taken in a single session. This therefore requires a plurality of biopsy brushes or tools, and a plurality of housings in which the tools are extended and retracted.

[0095] As discussed above, a positional insertion depth reference may be provided, such as a skirt type plug. However, when the multi-biopsy tool system has a mechanism held outside the orifice, the diameter of the tool can be large enough to act as the plug without additional structures.

[0096] According to one design, each biopsy tool is separate, including a housing control and guide wire. A set of biopsy tools is housed in an external tube housing. The tube has a tapered internal profile at the distal end so that a single biopsy tool can be advanced past the end of the housing into the orifice or channel from which a biopsy is to be taken. In some cases, endoscopic guidance of the biopsy is desired, in which case a second housing that supports the endoscope and illumination can also be advanced. The endoscope housing can also inject saline for visualization, although in the case of a brush biopsy this is unfavorable as the saline will wash away dislodged cells and reduce the positional accuracy of sampling. An inert gas, such as CO2, can also be injected through the casing in a known manner.

[0097] For example, the biopsy brush may be provided in a 3 mm tube, with 6 separate brushes provided within a housing. A stop may be provided at the proximal end of each housing within the housing to prevent over-withdrawal. Markings may be provided on each shell to inform the physician of the depth of insertion. In some cases, the physician may wish to sample incrementally at a series of depths in the orifice, and, advantageously, each respective casing may have a plug that limits its depth of insertion, and provides the physician with haptic feedback when that depth is reached. This plug can be a simple O-ring or clamp, which is adjusted by the doctor for each biopsy sampling tool before the procedure. The guide wire for each sampling tool may also have depth limits. Naturally, the retracted position with the biopsy tool fully withdrawn into the housing represents an extreme, and a clamp or limit may be provided at the manipulating end to control how far the guide wire can be extended beyond the end of the housing.

[0098] In this first design, each biopsy brush may be of the known type, with the optional addition of insertion and retraction limiters, and, in fact, housing for arranging a multiple biopsy sample session may be provided independently of the biopsy brushes. biopsy.

[0099] In general, the housing obviates the need for a separate skirt plug, although the housing may terminate in a skirt plug.

Example 3

[00100] According to a second design of the multi-sample biopsy device, a single manipulator extends from a housing, which itself contains a plurality of biopsy tools.

[00101] As discussed above, an insertion depth positional reference may be provided, such as a skirt-type plug. However, when the multi-biopsy tool system has a mechanism held outside the orifice, the diameter of the tool can be large enough to act as the plug without additional structures.

[00102] Thus, a selectively engageable coupling is provided between a single guide wire and the various tools. The coupling thus connects the guide wire, which extends to a doctor's manipulation interface, such as a gripping member, a handle, or a pivot mechanism, to the individual guide wire for each tool. Advantageously, the plurality of tools is provided in a rotating drum, which serves as a housing. Each biopsy tool, when engaged with the manipulation guide wire, can be advanced with its respective housing an insertion distance, and then the biopsy head advanced beyond the housing, and twisted or manipulated to obtain a biopsy sample. The biopsy head is then withdrawn back into the housing, the housing with biopsy head caps is then withdrawn back into the cartridge, and the barrel twisted so that another biopsy tool can then be engaged.

[00103] Therefore, the coupling is a coaxial coupling, which separately connects and controls the casing and the guide wire within each respective casing. For example, inside the cartridge, the end of the casing may terminate in a steel ring, which is magnetically permeable. Thus, a magnetic coupling can be used to connect and disconnect the housings. Additionally, inactive biopsy tools can also be held in place by another magnet, which is typically an electromagnet, or a permanent magnet with an electromagnetic release. The guide wire can be selectively connected to the external manipulation guide wire with a spring-loaded clamp. When the barrel is rotated, the spring-loaded clamp is released, and re-engages upon reaching the next detent position with the next biopsy tool aligned with the spring-loaded clamp. Within the barrel, the biopsy tool guide wire extends beyond the proximal end of the biopsy tool housing.

[00104] The barrel is typically at least as long as the desired insertion depth of the shell into the patient. Thus, if it is desired to have an insertion depth of 12 cm, the drum mechanism can be 13 to 16 cm long.

[00105] As shown in Fig. 12, a plurality of similar brushes are provided in a cartridge. In Fig. 13, a plurality of different brushes are provided in the cartridge. The cartridge has an exit port for the attached biopsy tool. Each brush has its own associated housing, which can be independently advanced onto the patient depending on which tool is engaged. A mechanism at the proximal end of the housing controls the selection of the drum position by a rotation angle, the locking of the casing of the respective active tool for tool feed control, the clamp clamping of the guide wire of the respective active tool for control of the guide wire for manipulation by the physician and, in some cases, other controls, such as casing deflection angle. Fig. 12 shows a bulb provided immediately proximal to each sampling brush, which is provided for drawing a sampling vacuum when the respective brush is withdrawn back into the housing.

[00106] Fig. 14 shows an end view of a portion of the mechanism in the drum, in which one guide wire is free to be manipulated by the doctor, while access for manipulating the other guide wires is locked. In Fig. 13, only one biopsy tool has this feature. Biopsy sampling tools may be, for example, an endocervical sampler, an endometrial sampler, a punch sampler, and a suction endometrial sampler.

[00107] In some cases, the housing itself may be pivotable or angularly orientable to direct the biopsy tool to a desired region. The pivotable housing may be a single axis geometry, i.e., a curvature of the end of the housing, typically as a result of a pull on a traction element, such as a cable, guide wire or filament affixed to the wall of the housing, not shown in the illustrations. figures. By controlling the bending angle and rotation angle of the casing relative to the organ, a reasonable range of control is provided. Similarly, a punch or loop or encapsulation biopsy device can also be controlled by a pull, which can be a thread or polymer filament. Thus, the case of a single guide wire with a single degree of freedom (advance/retraction) is a simpler case, and additional controls and degrees of freedom can be provided. Controls for these tools can also be selectively engaged through a mechanism, or provided individually to the user. An endoscopic imager (not shown in the figures) may preferably be provided as a feature of the housing so that it can be used with various biopsy tools within the housing. For example, a 1-3 mm endoscopic camera with fiber optic illumination can be provided, for example the On Semiconductor OVM6946 1/18” 400x400 imager.

Claims (14)

1. Tissue sampling device for endometrial biopsy characterized by comprising: a flexible casing (1) having a distal portion (7) configured to maintain an internal vacuum; a skirt-type plug (5), configured to support an external cervical canal of a human or animal, to maintain the casing at a fixed insertion depth through the cervical canal into a uterus of a human or animal; and a displaceable structure (2) within the housing, configured to form a coaxial structure (11); the displaceable structure having a first end (6) extending from a proximal end of the housing, and a second end (14) configured to, in a first state (8), extend from the distal portion (7) of the flexible housing (1) into the uterus, and in a second state (9), be retracted into the distal portion (7) of the flexible casing (1); the second end (14) of the displaceable structure having a cellular sampling structure (10), extending beyond a suction element (4) configured to slide against an inner wall of the distal portion to draw internal vacuum; and the coaxial structure (11) being configured for insertion at a predetermined depth (16) through the cervical canal into the uterus limited by a skirt-type plug (5), to obtain a biopsy sample, and to be removed from the cervical canal with the structure movable in the second state; and the coaxial structure (11) being configured such that a pull on the first end (6) of the displaceable structure (2) at the proximal end of the casing (1) results in a retraction of the displaceable structure (2) from the first state (8) for the second state (9), to generate the vacuum to cause a displacement of the medium external to the casing into the flexible casing (1) distal to the suction element (4). 2. Device, according to claim 1, characterized by the fact that the displaceable structure (2) ends at the second end (14) in an atraumatic bulb (12). 3. Device according to claim 1 or 2, characterized in that the cell sampling structure (10) comprises a brush (13). 4. Device according to claim 3, characterized in that the brush comprises a plurality of bristles extending radially from the displaceable structure (2). 5. Device according to any one of claims 3 or 4, characterized in that the brush (13) has a cross section that tapers in relation to the distance from the second end (14). 6. Device according to any one of claims 3 to 5, characterized by the fact that the brush (13) has a helical cross-section profile. 7. Device according to any one of claims 1 to 6, characterized in that the coaxial structure (11) is configured for insertion at a predetermined depth (16) through the cervical canal into the uterus of a human, to to retrieve an endometrial biopsy sample, and to be removed from the cervical canal of the uterus substantially uncontaminated. 8. Device according to any one of claims 1 to 6, characterized in that the coaxial structure (11) is further configured to be: inserted through the cervical canal into the uterus with the structure displaceable in the second state (9 ) to a predetermined depth (16) within the uterus; extended to the first state (8) with the cell sampling structure (10) within the uterus; manipulated by a user by moving the first end (6) of the displaceable structure to dislodge endometrial cells within the uterus; retracted to the second state (9) within the uterus, to cause the vacuum to draw a liquid sample surrounding the cell sampling structure (10) to the distal portion (7) of the flexible casing (1); and retracted from the cervical canal with the displaceable structure in the second state (9) to avoid contamination. 9. Device according to any one of claims 1 to 8, characterized in that the displaceable structure (2) comprises a flexible guide wire twisted in a spiral. 10. Device according to any one of claims 1 to 9, characterized in that the casing (1) has an outer diameter between 1 and 3 mm and a length between 20 and 50 cm. 11. Device according to any one of claims 1 to 10, characterized in that the skirt-type plug (5) comprises a flanged element on an external surface of the flexible casing (1), and the flexible casing (1) is configured for insertion through the cervical canal into a human uterus to the predetermined depth (16), to retrieve an endometrial biopsy sample from the interior of the uterus, and to be withdrawn from the cervical canal of the uterus after the biopsy sample is taken. endometrium be obtained, being further configured to be: inserted through the cervical canal into the uterus with the displaceable structure (2) in the second state (9) to the predetermined depth (16) with the distal end (3) of the flexible casing ( 1) inside the uterus; extended in the first state (8) with the cell sampling structure (10) within the uterus; manipulated by moving the first end (6) of the displaceable structure (2) to dislodge endometrial cells; retracted to the second state (9) within the uterus, to extract the vacuum to withdraw a liquid sample surrounding the cell sampling structure (10) to the distal portion of the flexible casing (1); and retracted from the cervical canal with the displaceable structure (2) in the second state (9). 12. Device according to any one of claims 1 to 11, characterized by the fact that the suction element (4) that creates a negative pressure within the flexible casing (1) when the displaceable structure (2) is removed to the flexible casing (1) in the second state (9) comprises a piston. 13. Device according to any one of claims 1 to 12, characterized in that it comprises: a plurality of flexible casings (20), each having a respective suction element (21) configured to maintain an internal vacuum in a distal portion ( 7) a respective flexible casing (20); a respective displaceable structure (22) within each flexible casing (20), configured to form a set of coaxial structures; and a housing (23), configured to selectively affix a respective displaceable structure (20) to a user interface (24), such that when engaged, tension and compression are passed from the user interface (24) to the structure displaceable (20) to transition the displaceable structure (20) between the first state (8) and the second state (9); and when disengaged, tension and compression are not passed from the user interface (24) to the displaceable structure (20). 14. Device for multiple sample biopsy characterized by comprising: a plurality of flexible casings (20); a displaceable structure within each casing (22) to form a coaxial structure; each displaceable structure (22) having a first end extending from a proximal end of the flexible housing (20) and a second end (26) configured to, in a first state (8), extend from a distal portion ( 7) of the flexible housing (20) to expose a biopsy device (25) comprising a cell sampling structure, and in a second state (9), be retracted into the distal portion (7) of the flexible housing (20) to protect the biopsy device (25), wherein the coaxial structure is configured to be withdrawn from a channel after obtaining the biopsy in the second state (9); and a housing (23), configured to selectively affix a respective displaceable structure (22) to a user interface (24), such that when engaged, tension and compression are passed from the user interface (24) to the displaceable structure (22) to transition the displaceable structure (22) between the first state (8) and the second state (9) and, when disengaged, tension and compression are not passed from the user interface (24) to the displaceable structure (22).