WO2011140374A1

WO2011140374A1 - Tissue analysis instrument

Info

Publication number: WO2011140374A1
Application number: PCT/US2011/035401
Authority: WO
Inventors: Emre Toker; Lauren Grasso-Lebeau; Mark Banister; Julie Lang; Scott Conley; Xenia Kachur
Original assignee: Surgical Tools, Llc
Priority date: 2010-05-07
Filing date: 2011-05-05
Publication date: 2011-11-10

Abstract

A tissue gross pathology containment, encapsulation, sectioning and analysis system includes a specimen container with removable side walls and a flexible base detachable into a plurality of sections wherein the container is marked with specimen placement information correlated with the three-dimensional orientation of the tissue in-vivo prior to excision, and a platform material that may include a gel-type compound to fill the container and encapsulate the specimen inside the container wherein the gel is a cured solid which is soft, transparent and easily sliceable with a surgical blade and a plurality of rods extending substantially perpendicular from the base and being spaced along the longitudinal direction of the base substantially distal from the specimen placed in the container.

Description

TISSUE ANALYSIS INSTRUMENT

Cross Reference to Related Applications

This application claims priority to U.S. Provisional Application No. 61/332,278, filed May 6, 2010, the contents of which are incorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The present invention relates in general to tissue analysis in surgical pathology and, in particular, for the identification and localization of information relating to abnormal regions in tissue. The present invention has particular advantages with respect to breast-conserving surgery procedures.

BACKGROUND OF THE INVENTION

Testing margins of surgically excised breast tissue samples for the presence of cancer during lumpectomy procedures is the standard of care (Westra, 2003), since the presence of cancer at excision margins can be an indication of cancer left behind in the breast, causing local recurrence of breast cancer, or requiring re-excisions. Current conventional techniques to detect positive surgical margins of excised breast tissue during lumpectomy procedures are gross pathologic examination, frozen section histopathology and touch imprint cytology. The average time to obtain results with these techniques is approximately 20 minutes (Prophet, Mills, & Arrington, 1992). Therefore, such techniques are used to detect positive surgical margins of excised breast tissue while the patient is on the operating table. However, outcomes of these techniques are very subjective and depend on the experience of the pathologist. Sensitivity and specificity of frozen section histopathology and touch imprint cytology varies greatly (Zgajnar, et al., 2004) (Geomini, Bremer, & Kruitwagen R, 2005) (Cikojevic, Gluncic, & Pesutic-Pisac, 2008) (Huang, 2007). The gold standard for defining positive surgical margins and sentinel lymph node status is permanent section histopathology (Westra, 2003). However, permanent section histopathology results are available only long after the patient leaves the operating room. Thus, positive surgical margins and lymph nodes identified by permanent section histopathology generally require undesirable repeat surgeries.

In gross pathologic examination of excised tissue, it is often important and sometimes critical, such as in breast-conserving surgery, to not just detect the presence of cancer at the margins of the excised tissue, but also to determine which surface of the excised tissue surface cancer was detected. Identification of cancer-positive surfaces allows the pathologist to inform the surgeon where additional tissue must be excised. Typically, each of the six surfaces of the excised tissue sample, superior, inferior, medial, lateral, anterior and posterior are each painted with a different color dye, in a process called "differential inking" to identify which surfaces cancer cells were detected on. Typically, the specimen is sectioned or sliced into slices of approximately equal thickness with the aid of a surgical blade and each slice is individually inspected for evidence of cancer at the margins (Weidner, Cote, Suster, & Weiss, 2003).

The problem that arises with differential inking is that "improper use of these inks can befuddle the microscopic findings" (Westra, 2003).

SUMMARY OF THE INVENTION

Embodiments of the present invention are directed to the identification and localization of abnormal cells in tissue. The embodiments of the invention thus allow for the placement of excised tissue within a specimen container such that the orientation of the specimen within the container is substantially correlatable to the orientation of the tissue within the human body prior to excision.

The present invention further allows for the sectioning of tissue into slices of uniform thickness and the inspection of individual slices for the presence of cancer.

The present invention further allows for the re-assembly of the sliced tissue into substantially original form while preserving its three dimensional orientation.

In accordance with the present invention, regions on the tissue surface containing abnormal cells are identified and localized by analysis of individually sliced sections of the tissue. An associated apparatus includes a specimen container with removable side walls and a flexible base detachable into a plurality of sections wherein the container is marked with specimen placement information to correlate with the three-dimensional orientation of the tissue in-vivo prior to excision, a platform material for capturing the specimen in a single orientation in the container, wherein the platform material is soft and easily sliceable with a surgical blade. The platform material may be, in one embodiment, a gel-type compound to fill the container and encapsulate the specimen inside the container wherein the gel is a fast setting cured solid which is soft, transparent and easily sliceable with a surgical blade. The apparatus may also include a plurality of labeled rods extending substantially perpendicular from the base and being spaced along the longitudinal direction of the base substantially distal from the specimen placed in the container. BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention and further advantages thereof, reference now made to the following Detailed Description taken in conjunction with the drawings in which:

FIG. 1 is a perspective view of a specimen container in accordance with a preferred embodiment of the present invention

FIG. 2 is a perspective view of the slicing of an encapsulated tissue into sections of equal thickness in accordance with a preferred embodiment of the present invention FIG. 3 is a perspective view of a representative individual specimen slice in accordance with the preferred embodiment of the present invention.

FIG. 4 is a photograph of a specimen sample encapsulated in a gel compound in accordance with a preferred embodiment of the present invention.

FIG. 5 is a photograph of the slicing of an encapsulated specimen into sections in accordance with a preferred embodiment of the present invention.

FIG. 6 is a photograph of representative individual specimen slices in accordance with the preferred embodiment of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Embodiments of the invention are directed to a pathology gross examination apparatus comprising a specimen container with substantially transparent, removable side walls and a flexible base detachable into a plurality of sections, wherein the container is marked with specimen placement information to correlate with the three- dimensional orientation of the tissue in-vivo prior to excision. To immobilize the tissue specimen in a single orientation for further tissue processing, a platform material for capturing the specimen in a single orientation in the container is provided in the container wherein the platform material is soft and easily sliceable with a surgical blade. The platform material may be a tissue-processing compatible material such as a gel, a paraffin wax, or a porous polymer such as is used in tissue processing cassettes.

The container may be partially pre-filled with a platform material such as a gel- type compound, wherein the gel is soft and easily sliceable with a surgical blade. The pre-filled gel makes a platform upon which the tissue specimen may be placed prior to being filled with warm, liquefied gel that will subsequently set and entrap the tissue specimen within a matrix of gel and in a single orientation.

Yet another embodiment of the invention is a method for correlating the original location of a tissue biopsy, comprising providing the pathology gross examination container apparatus, then placing a tissue biopsy in said container in the same orientation with respect to the body from which it was taken according to the standard medical definitions of superior, anterior and medial then subjecting the tissue biopsy to an analytical protocol, and finally correlating any portion of the biopsy with the original body orientation.

Yet a further embodiment of the invention is directed to a pathology gross examination apparatus comprising a specimen container having removable side walls; a flexible base demarcated into a plurality of sections, wherein each individual section of the container is marked with specimen placement information to correlate with the three- dimensional orientation of the tissue in-vivo prior to excision; and a plurality of rods extending substantially perpendicularly from the flexible base and spaced along the longitudinal direction of the flexible base substantially distal from the specimen placed in the container.

FIG. 1 is a perspective view of a specimen container in accordance with a preferred embodiment of the present invention. The container 100 consists of a specimen container with side walls 101 composed of a material such as glass or plastic. The material may be substantially transparent, or it may be opaque. In a preferred embodiment the material is substantially visually transparent. Orientation information including the superior aspect 102, posterior aspect 103, and medial aspect 104 are indicated on the corresponding walls 101 of the container 100. Also indicated on the base of the container are numerical slice numbers 105, starting from the medial aspect and numbered numerically from 1 to the desired number of slices and ending with the lateral aspect. The numbering system may be either designed to be read by a human, or read by a machine. Human-readable indicia are commonly alpha-numeric systems printed, etched, embossed, stamped or otherwise made visually accessible either directly on the container, or on a label affixed to the container. Machine-readable systems include Optical Character Recognition ("OCR") where a computer-aided scanner scans the container and/or a label containing identifying digital information, then correlates the digital information with a database containing look-up tables having entries

corresponding to the specimen. Other forms of machine-readable specimen information include Radio Frequency Identification ("RFID") and bar codes. It will be apparent to one of ordinary skill in the art that there are numerous choices to use when considering the type of information encoding to use on a container used in medical sample processing. It will be appreciated that the specimen container may be constructed in various sizes to accommodate a variety of tissue sizes, for example from 1 cm x 1 cm x 1 cm to 20 cm x 20 cm x 20 cm. Other container sizes can be envisioned to accommodate larger or smaller tissue samples. The types of tissue samples will determine the size of the container, and samples as small as fine needle aspirates and punch biopsies to large pieces of organ tissue may be accommodated. It will also be appreciated that the number of slices can be selected to accommodate thinner or thicker slices as desired, for example, from 1 mm thickness to 5 mm. Other thinner or thicker slice thicknesses can be envisioned.

A platform material is used within the container to capture the specimen in a single orientation in the container so that the specimen placement information correlates with the three-dimensional orientation of the tissue in-vivo prior to excision. The platform material may be permanently attached in the container, or it may be added to the container after the end user has acquired it. In one embodiment a platform material is soft and easily sliceable with a surgical blade, such as a histological-quality gel, or a paraffin wax. In a preferred embodiment, the platform material is a gel-like substance. The container may come from the manufacturer partially filled with the gel so that a semi-solid platform is provided that holds the tissue specimen off the bottom of the container. After the tissue specimen is placed on the gel platform oriented to correlate with the in vivo tissue orientation, liquefied gel is then poured into the container, which as it cools locks the tissue specimen in one orientation.

In a particularly preferred embodiment the container can be filled with gel-type compounds 106, such as polyethylenimine and poly (ethyleneglycol) diglycidyl ether, which, when cured, becomes a soft, transparent and easily sliceable solid. These gels are typically designed for tissue processing, such as HISTO-GEL™ brand embedding gel, Richard-Allan Scientific, Kalamazoo, MI. The tissue specimen 107 can be lowered into the gel 106 prior to curing with a pair of tweezers 108 such that the specimen is suspended in the gel 106 without coming into contact with any of the walls 101 or the base 109 of the container 100. Paraffin wax can also be pre-loaded into the container to provide a platform if the container is to be used in tissue embedding operations.

The base 109 of the container 100 is composed of a flexible material such as a soft plastic, such as Solid Concepts Inc. Models SC 1000 and FC 130, and is divided into breakable sections identified by the slice numbers 105 indicated on the container 100. A plurality of anterior rods 110 and a plurality of posterior rods 111 extend substantially perpendicular from the base 109 of the container 100. The rods are composed of a hard plastic material such as Solid Concepts Inc. models Nylon 12 AF and SC 4500. The rods serve two functions. The gel slices 301 and the encapsulated specimen slice 302 are held firmly by the anterior rods 110 and the posterior rods 111 within the representative gel slice 301 in order to provide guides for the knife path during slicing, and to demarcate the boundaries.

A specimen container can be constructed in accordance with preferred embodiments of the present invention utilizing plastic injection molding techniques apparent to one of ordinary skill in plastic injection molding. In accordance with preferred embodiments of the present invention, a plurality of thermoplastic materials are suitable for construction, including polypropylenes, polyurethanes, and polycarbonates. One having ordinary skill in the art will be able to select those materials that are appropriate for the tissue processing environment where reagents such as water, alcohols, aliphatic hydrocarbon liquids such as xylene, and paraffin are in use.

Preferred embodiments of the present invention can be constructed in a plurality of sizes, ranging from several centimeters to tens of centimeters, in accordance with commonly encountered specimen sample sizes. Similarly, rod spacing can also be offered ranging from several millimeters to tens of millimeters, in accordance with commonly encountered specimen sizes.

FIG. 2 is a perspective view of the slicing of an encapsulated tissue into sections of equal thickness in accordance with a preferred embodiment of the present invention. Once the gel material 106 encapsulating the tissue specimen 107 is cured into a substantially solid form, the side walls 101 of the container 100 are removed, exposing the gel 106 encapsulating the specimen 107. A surgical blade 201 is then used to slice the gel 106 and the specimen 107 into slices of substantially equal thickness by running the surgical blade 201 in between the anterior rods 110 and posterior rods 111.

FIG. 3 is a perspective view of a representative individual specimen slice in accordance with the preferred embodiment of the present invention. A representative individual slice of the gel 301 encapsulates a representative individual specimen slice 302 of the tissue specimen 107. The gel slice 301 and the encapsulated specimen slice 302 are held firmly by the anterior rods 110 and the posterior rods 111 within the representative gel slice 301 in order to provide guides for the knife path during slicing as well as demarcate the boundaries. Each specimen slice 302 can be removed from the assembly by flexing the base 109 of the container 100. The entire specimen 107 can be reconstructed into a whole by inserting each specimen slice 302 into its original location in the assembly, aided by the numbering system M1 -M9, [etcj.

FIG. 4 is a photograph of a specimen sample 402 encapsulated in a gel compound 401 in accordance with a preferred embodiment of the present invention. The technology is applicable to many cancers in which surgical excision of the cancerous tissue is necessary including breast, prostate, melanoma, and kidney. The average sizes of breast, prostate, melanoma, and kidney specimens are estimated at 560 cm³, 60 cm³, 3 cm³, and 216 cm³, respectively.

FIG. 5 is a photograph of the slicing of an encapsulated specimen 503 into sections 502 utilizing a surgical blade 501 in accordance with a preferred embodiment of the present invention. The numbering system is used to quantitatively identify the location of the tumor in the excised specimen; for example, if the tumor is in slice 6 on the lateral orientation marker side, the pathologist can recommend that the surgeon removes more tissue in that specific area of the surgical cavity.

FIG. 6 is a photograph of representative individual specimen slices 601 each encapsulating a slice of the specimen 602 in accordance with the preferred embodiment of the present invention. The gel is designed to be compatible with 10% formalin solutions and subsequent tissue processing steps such as tissue dehydration, paraffin imbedding, and staining are not affected.

It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. Those skilled in the art will envision other modifications that come within the scope and spirit of the claims appended hereto. All patents and references cited herein are explicitly incorporated by reference in their entirety.

References

Cikojevic, Gluncic, & Pesutic-Pisac. (2008). Comparison of contact endoscopy and frozen section histopathology in the intra-operative diagnosis of laryngeal pathology. J Laryngol Otol„ \ 22(S):S36-9.

Geomini P, et al. (2005). Diagnostic accuracy of frozen section diagnosis of the adnexal mass: a metaanalysis. Gynecol Oncol., 96( 1 ): 1.

Huang, W. et al. (2007). Evaluation of intraoperative touch imprint cytology of sentinel lymph node for breast cancer. Zhonghua Z ong Liu Za Zhi, 29(8):596-9. Weidner, Cote, Suster, & Weiss. (2003). Modern Surgical Pathology. Philadelphia: Saunders.

Westra, W. (2003) Surgical pathology dissection. 2^nd ed. New York.

Prophet, Mills, & Arrington. (1992). Laboratory Methods in Histotechnology.

Washington DC.

Zgajnar, Frkovic-Grazio, Besic, Hocevar, Vidergar- ralj, Gerljevic, et al. (2004). Low sensitivity of the touch imprint cytology of the sentinel lymph node in breast cancer patients— results of a large series. Journal of Surgical Oncology, 85: 82-86.

Claims

CLAIMS What is claimed is:

1 . A pathology gross examination apparatus comprising:

a specimen container with removable side walls and a flexible base detachable into a plurality of sections, wherein the container is marked with specimen placement information to correlate with the three-dimensional orientation of the tissue in-vivo prior to excision; and

a platform material for capturing the specimen in a single orientation in the container, wherein the platform material is soft and easily sliceable with a surgical blade.

2. The pathology gross examination apparatus according to claim 1, wherein a plurality of rods extends substantially perpendicular from the base and is spaced along the longitudinal direction of the base substantially distal from the specimen placed in the container.

3. The pathology gross examination apparatus according to claim 1 , wherein individual specimen slices can be removed from and re-inserted into the apparatus in their original sequence by reference to the specimen placement information.

4. The pathology gross examination apparatus according to claim 1 , wherein the side walls are substantially visually transparent.

5. The apparatus of claim 1 wherein the platform material comprises a paraffin-like compound that at least partially fills the container, wherein the paraffin is soft and easily sliceable with a surgical blade.

6. The apparatus of claim 1 wherein the platform material comprises a gel-like compound permeable to tissue processing reagents.

7. The apparatus of claim 1 wherein the platform material at least partially fills the container, and wherein the platform material is soft and easily sliceable with a surgical blade.

8. The apparatus of claim 1 wherein the specimen placement information comprises a human-readable numbering system.

9. The apparatus of claim 1 wherein the specimen placement information comprises a machine-readable numbering system.

10. The apparatus of claim 9 wherein the machine readable numbering system is selected from the group consisting of bar codes, OCR, and RF1D.

1 1 . A method for correlating the original location of a tissue biopsy, comprising: (a) providing the container apparatus of claim 1 ;

(b) placing a tissue biopsy in said container in the same orientation with respect to the body from which it was taken;

(c) subjecting the tissue biopsy to an analytical protocol; and

(d) correlating any portion of the biopsy with the original body orientation.

12. A pathology gross exam ination apparatus comprising:

a specimen container having removable side walls;

a flexible base demarcated into a plurality of sections, wherein each individual section of the container is marked with specimen placement information to correlate with the three-dimensional orientation of the tissue in-vivo prior to excision; and

a plurality of rods extending substantially perpendicularly from the flexible base and spaced along the longitudinal direction of the flexible base substantially distal from the specimen placed in the container.

13. The apparatus of claim ! 2 wherein a platform material for capturing the specimen in a single orientation is located in the container, wherein the platform material is soft and easily sliceable with a surgical blade.

14. The apparatus of claim 12 wherein the platform material comprises a gel-type compound that at least partially fills the container, wherein the gel is soft and easily sliceable with a surgical blade.

15. The apparatus of claim 12 wherein the platform material comprises a paraffin-like compound that at least partially fills the container, wherein the paraffin is soft and easily sliceable with a surgical blade.

16. The apparatus of claim 12 wherein the specimen placement information comprises a human-readable numbering system.

17. The apparatus of claim 12 wherein the specimen placement information comprises a machine-readable numbering system,

18. The apparatus of claim 1 7 wherein the machine readable numbering system is selected from the group consisting of bar codes, OCR, and RFID.

19. The apparatus of claim 12 wherein the side walls are substantially visually transparent.

20. A method for correlating the original location of a tissue biopsy, comprising:

(a) providing the container apparatus of claim 12;

(b) placing a tissue biopsy in said container in the same orientation with respect to the body from which it was taken; (c) subjecting the tissue biopsy to an analytical protocol; and

(d) correlating any portion of the biopsy with the original body orientation.