U.S. patent application number 09/740561 was filed with the patent office on 2001-05-10 for method and kit for obtaining fluids and cellular material from breast ducts.
This patent application is currently assigned to The Regents of the University of California.. Invention is credited to Love, Susan M..
Application Number | 20010001059 09/740561 |
Document ID | / |
Family ID | 22077527 |
Filed Date | 2001-05-10 |
United States Patent
Application |
20010001059 |
Kind Code |
A1 |
Love, Susan M. |
May 10, 2001 |
Method and kit for obtaining fluids and cellular material from
breast ducts
Abstract
Methods, kits, and apparatus for obtaining cellular, chemical,
and other materials from breast ducts are described. A single milk
duct is accessed and washed with a washing fluid to obtain marker
materials from the lining the duct. The washing fluid is then
collected, and the marker materials in the washing fluid identified
and analyzed. Usually, the washing fluid is introduced using a
syringe through a lumen of a dual-lumen catheter. The ductal volume
is filled with the washing fluid and excess fluid flows outwardly
through a second lumen of the dual-lumen catheter, from which it is
collected.
Inventors: |
Love, Susan M.; (Pacific
Palisades, CA) |
Correspondence
Address: |
Attention: William J. Wood
Gates & Cooper
Howard Hughes Center
6701 Center Drive West, Suite 1050
Los Angeles
CA
90045
US
|
Assignee: |
The Regents of the University of
California.
|
Family ID: |
22077527 |
Appl. No.: |
09/740561 |
Filed: |
December 19, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09740561 |
Dec 19, 2000 |
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09067661 |
Apr 28, 1998 |
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Current U.S.
Class: |
435/7.1 ;
604/508 |
Current CPC
Class: |
A61B 10/0045
20130101 |
Class at
Publication: |
435/7.1 ;
604/508 |
International
Class: |
A61M 031/00 |
Goverment Interests
1. This invention was made with Government support under contract
DAMD17-96-C-6117. The government has certain rights in this
invention.
Claims
What is claimed is:
1. A method for obtaining material from a milk duct in a breast of
a patient, said method comprising: (a) locating a single milk duct;
(b) introducing a washing fluid substantially throughout the duct
without rupture; (c) collecting at least a portion of the washing
fluid from the duct; and (d) identifying materials in the washing
fluid collected from the duct.
2. A method as in claim 1, further comprising obtaining material
from at least one additional single mile duct of the same breast by
repeating steps (a) through (d) on another single milk duct.
3. A method as in claim 2, wherein the steps are repeated for all
ducts in the nipple.
4. A method as in claim 1, wherein the materials identified in the
washing fluid include ductal epithelial cells.
5. A method as in claim 4, further comprising examining the
morphology of the epithelial cells in the washing fluid to
determine if they are atypical in order to assess the likelihood of
a cancer present in the cellular lining of the duct.
6. A method as in claim 1, wherein the materials comprise molecular
species.
7. A method for obtaining material from a milk duct in a breast of
a patient, said method comprising: (a) locating at least one of the
ductal orifices on a nipple of the breast; (b) introducing a
catheter having at least one lumen through one of the ductal
orifices and into the ductal passage; (c) introducing a washing
fluid through a lumen into the ductal passage; (d) collecting the
washing fluid from the ductal passage through a lumen of the
catheter; and (e) identifying materials present in the collected
washing fluid.
8. A method as in claim 7, further comprising dilating the ductal
orifice prior to introducing the catheter.
9. A method as in claim 7, wherein the catheter includes at least
two lumens and washing fluid introducing and collecting steps are
performed through separate lumens in the catheter.
10. A method as in claim 9, wherein a preselected volume of the
washing fluid is introduced to the duct through one lumen and
excess volume flows out of the duct through another catheter
lumen.
11. A method as in claim 10, wherein the volume of washing fluid is
at least 5 ml.
12. A method as in claim 8, wherein the volume of washing fluid is
at least 10 ml.
13. A method as in claim 7, further comprising obtaining and
identifying material from at least one additional single milk duct
of the same breast by repeating steps (a) through (e) on another
single milk duct.
14. A method as in claim 13, wherein the steps are repeated for all
ducts in the nipple.
15. A method as in claim 6, wherein the material in the washing
fluid include epithelial cells.
16. A method as in claim 15, further comprising examining the
morphology of the epithelial cells in the washing fluid to
determine if they are atypical in order to assess the likelihood of
a cancer present in the cellular lining of the duct.
17. A method as in claim 7, wherein the materials comprise
molecular species.
18. A kit for obtaining material from a milk duct of a breast, said
kit comprising: a catheter; and instructions setting forth a method
for use of the dual-lumen catheter according to claim 7.
Description
BACKGROUND OF THE INVENTION
2. 1. Field of the Invention
3. The present invention relates generally to medical methods and
apparatus for obtaining fluids and cellular materials from a
patient. More particularly, the present invention relates to
methods and apparatus for obtaining epithelial cells from the
lining of a breast milk duct.
4. Breast cancer is the most common cancer in women, with well over
100,000 new cases being diagnosed each year. Even greater numbers
of women, however, have symptoms associated with breast diseases,
both benign and malignant, and must undergo further diagnosis and
evaluation in order to determine whether breast cancer exists. To
that end, a variety of diagnostic techniques have been developed,
the most common of which are surgical techniques including core
biopsy and excisional biopsy. Recently, fine needle aspiration
(FNA) cytology has been developed which is less invasive than the
surgical techniques, but which is not always a substitute for
surgical biopsy.
5. A variety of other diagnostic techniques have been proposed for
research purposes. Of particular interest to the present invention,
fluids from the breast ducts have been externally collected,
analyzed, and correlated to some extent with the risk of breast
cancer. Such fluid collection, however, is generally taken from the
surface of the nipple and includes material from all of the ductal
structures. Information on the condition of an individual duct is
generally not provided. Information on individual ducts can be
obtained through cannulation and endoscopic or fluoroscopic
examination, but such examinations have been primarily in women
with nipple discharge or for research purposes and have generally
not examined each individual duct in the breast.
6. Since breast cancer usually arises from a single ductal system
and exists in a precancerous state for a number of years, endoscopy
in and fluid collection from individual breast ducts holds great
diagnostic promise for the identification of intermediate markers.
Of particular interest to the present invention, it would be of
great value to be able to reliably collect ductal fluids and
cellular and non-cellular marker materials (e.g. epithelial and
other cells as well as proteins, carbohydrates, and other
non-cellular marker materials) from the individual breast ducts on
a duct-by-duct basis. By examining the collected marker materials,
cancerous and pre-cancerous conditions within each duct could be
identified at a very early stage. Moreover, by associating the
condition with a specific duct, treatment could be directed
specifically at that duct in an attempt to enhance the
effectiveness of the treatment and minimize trauma to the
patient.
7. The ability to perform such diagnostic techniques, however, has
been limited. Heretofore, it has been very difficult to identify
ductal orifices in a reliable and consistent manner. That problem,
however, has been addressed by the invention reported in
co-pending, commonly assigned Application Ser. No. 08/931,786,
filed on Sep. 16, 1997, the full disclosure of which is
incorporated herein by reference. By labeling the ductal orifices,
the location of the entry orifice for each duct can be
established.
8. Even though access to all of the ducts in a breast can now be
achieved, successful diagnostic methods will depend on the ability
to collect cellular and non-cellular materials from at least, most,
and preferably all, regions of each ductal network. Breast ducts
have highly complex and convoluted three-dimensional geometries,
with more remote portions of the network having increasingly
smaller diameters. Thus, obtaining representative material samples
from throughout a ductal network represents a significant
challenge.
9. Prior attempts to obtain cellular material from individual
breast ducts have been only partly successful. As reported by the
inventor herein, in Love and Barsky (1996) The Lancet 348:997-999,
breast ducts have been cannulated with a rigid cannula and
instilled with very small volumes (0.2 ml to 0.5 ml) of saline.
Saline was recovered separately through a capillary tube, and
cellular material recovered from the saline. It was not clear,
however, if cellular material was recovered from most or all
portions of the ductal network. Unless such representative samples
can be obtained, reliable diagnostics cannot be performed. While
the paper proposes development of a two-lumen catheter, no such
catheter or its use is described in the publication.
10. For these reasons, to enable the performance of ductal
diagnostic techniques, it will be useful to provide methods and
apparatus which permit the collection of fluids and marker
materials from individual ductal networks in a reliable and
consistent fashion. Such methods should be minimally traumatic to
the patient, should be useful for routine screening in at least
high-risk patients, and should provide cellular and non-cellular
materials suitable for reliable detection of cancerous and
pre-cancerous conditions. At least some of these objectives will be
met by the invention described hereinafter.
11. 2. Description of the Background Art
12. Publications by the inventor herein relating to breast duct
access include Love and Barsky (1996) Lancet 348: 997-999; Love
(1992) "Breast duct endoscopy: a pilot study of a potential
technique for evaluating intraductal disease," presented at 15th
Annual San Antonio Breast Cancer Symposium, San Antonio, Tex.,
Abstract 197; Barsky and Love (1996) "Pathological analysis of
breast duct endoscoped mastectomies," Laboratory Investigation,
Modern Pathology, Abstract 67. A description of the inventor's
earlier breast duct access work was presented in Lewis (1997)
Biophotonics International, pages 27-28, May/June 1997.
13. Nipple aspiration and/or the introduction of contrast medium
into breast ducts prior to imaging are described in Sartorius
(1995) Breast Cancer Res. Treat. 35: 255-266; Satorious et al.
(1977) "Contrast ductography for the recognition and localization
of benign and malignant breast lesions: An improved technique," in:
Logan (ed.), Breast Carcinoma, New York, Wiley, pp. 281-300;
Petrakis (1993) Cancer Epidem. Biomarker Prev. 2: 3-10; Petrakis
(1993) Epidem. Rev. 15: 188-195; Petrakis (1986) Breast Cancer Res.
Treat. 8: 7-19; Wrensch et al. (1992) Am. J. Epidem. 135: 130-141;
Wrensch et al. (1990) Breast Cancer Res. Treat. 15: 39-51; and
Wrensch et al. (1989) Cancer Res. 49: 2168-2174. The presence of
abnormal biomarkers in fine needle breast aspirates is described in
Fabian et al. (1993) Proc. Ann. Meet. Am. Assoc. Cancer Res. 34:
A1556. The use of a rigid 1.2 mm ductoscope to identify intraductal
papillomas in women with nipple discharge is described in Makita et
al. (1991) Breast Cancer Res. Treat. 18: 179-188. The use of a 0.4
mm flexible scope to investigate nipple discharge is described in
Okazaki et al. (1991) Jpn. J. Clin. Oncol. 21: 188-193. The
detection of CEA in fluids obtained by a nipple blot is described
in Imayama et al. (1996) Cancer 78: 1229-1234. Delivery of
epithelium-destroying agents to breasts by ductal cannulation is
described in WO 97/05898.
SUMMARY OF THE INVENTION
14. The present invention provides improved methods, kits, and
other apparatus for obtaining fluids, marker substances, cellular
material, and the like (referred to hereinafter as "marker
materials") from single milk ducts in the breasts of human female
patients. In particular, the methods of the present invention
permit reliable washing and retrieval of marker materials from an
entire network of a single milk duct to enable screening,
diagnosis, and monitoring of diseases associated with the lining of
the milk duct, particularly for identifying cancer and
pre-cancerous conditions. As the marker materials are obtained
entirely from a single ductal network, diagnosis can be made on a
duct-by-duct basis. By obtaining specimens from each one of the
multiple ductal networks in a breast, however, the presence of
disease or increased likelihood of disease in the entire breast can
also be determined.
15. In a first aspect of the present invention, a method for
obtaining marker materials from a milk duct of a breast comprises
locating a single milk duct, typically by labeling a ductal orifice
present in the nipple of the breast. A washing fluid, typically
saline, is introduced into the duct so that it passes substantially
throughout the entirely ductal network, preferably without
rupturing the duct. At least a portion of the washing fluid is then
collected from the duct, and marker materials which may be present
in the collected fluid (including fluids which might otherwise be
secreted) are identified. While in some cases it may be desirable
to collect specimens from only a single ductal network, it will
usually be preferred to repeat the steps in order to identify the
presence of marker materials in each of the ductal networks present
in the breast. Cellular marker materials may comprise epithelial
cells from the lining of the duct while the fluids will comprise
normally secreted and non-secreted fluids present in the ducts. The
epithelial and other cells obtained by the method will usually be
morphologically histochemically, and/or immunohistochemically
examined to determine if they are abnormal and to assess the
likelihood of a cancer or pre-cancerous condition present in the
cellular lining of the duct. Non-cellular marker materials include
proteins, peptides, and other chemical species which may be
secreted or otherwise released into a duct in response to a disease
or other condition to be identified.
16. In a further aspect of the present invention, a preferred
method for obtaining marker materials from a milk duct of a breast
comprises locating at least one of the ductal orifices on the
breast nipple. A dual-lumen catheter is then introduced through the
orifice and into the ductal passage, usually over a guidewire. A
washing fluid is then introduced through one of the lumens into the
duct. Sufficient fluid is introduced so that the fluid will
substantially fill the ductal volume and will then pass outwardly
through the other of the catheter lumens so that it may be
collected externally to the breast. Marker materials, such as
epithelial and other cells, present in the collected washing fluid
may then be isolated, detected and/or examined, as generally
described above. Additionally, the ductal fluids present in the
ducts prior to introduction of the washing fluid will be diluted
and collected and may be examined for the presence of both small
molecules and macromolecules, including proteins, carbohydrates,
and other potential disease markers.
17. The volume of washing fluid introduced into the ductal network
will usually be at least 5 ml, preferably being from 5 ml to 25 ml,
usually being about 10 ml. The washing fluid will typically be
introduced through the catheter lumen using a syringe at a
generally low pressure which will not result in rupture of the
ductal network. The washing fluid will be introduced over a
relatively short time period, typically from 1 minute to 5 minutes,
and will continue to be introduced even after the initial portions
of the fluid begin to emerge from the second catheter lumen. As
before, the method will usually be repeated for each of the ductal
networks present in the breast.
18. According to yet a further aspect of the present invention, a
kit for obtaining marker materials from a breast duct comprises a
dual-lumen catheter together with instructions setting forth a
method for use as described above. The kit will usually further
comprise a package, such as a pouch, tray, tube, box, or the like.
The instructions for use may be printed on a separate piece of
paper, or optionally may be printed in whole or in part on a
portion of the packaging. Usually, the dual-lumen catheter will be
sterilized and maintained in a sterile condition within the
packaging. Optionally, other system components, such as guidewires,
saline or other washing fluid(s), cell growth and maintenance
media, cell fixation media, cell collection trays, or the like,
could be provided as part of the kit.
BRIEF DESCRIPTION OF THE DRAWINGS
19. FIG. 1 is an anterior view of a human female breast, shown in
section, and illustrating three of the six to nine ductal networks
extending inwardly from the nipple.
20. FIG. 2 is an enlarged view of the nipple of FIG. 1 illustrating
the orifices leading to each of the three ductal networks.
21. FIG. 3 is a perspective view of a dual-lumen catheter which is
useful in performing the methods of the present invention.
22. FIG. 4 is a detailed view of the distal end of the catheter of
FIG. 3, shown in section.
23. FIG. 5 illustrates use of the catheter of FIG. 3 in performing
the method of the present invention in a single ductal network.
24. FIG. 6 illustrates a kit comprising a dual-lumen catheter and
other system components, including instructions for use.
25. FIGS. 7A-7C illustrate the catheter utilized in the working
examples hereinafter.
DESCRIPTION OF THE SPECIFIC EMBODIMENTS
26. The present invention comprises methods and kits for obtaining
marker materials from one or more ductal networks in a human female
breast. A typical breast B, as illustrated in FIG. 1, includes a
nipple N and from six to nine ducts D. Three ductal networks
D.sub.1-3 extending inwardly from the nipple N into the breast
tissue are illustrated. As best seen in FIG. 2, each ductal network
D.sub.1-3 begins with an orifice O.sub.1-3 which lies at the
surface of the nipple N and extends inwardly through a ductal sinus
S.sub.1-3 and then into a branching network. Each network D
comprises a series of successively smaller lumens which are
arranged in complex, three-dimensional patterns. The networks of
each duct will overlap within the breast tissue but will not be
interconnected. The total volume of each network is usually in the
range from 0.1 ml to 0.5 ml, but the walls are somewhat compliant
so the internal volume may increase as fluid is introduced. The
present invention relies on accessing the ductal network(s) through
the orifice O of the duct D within the nipple N. Usually, there
will be from six to nine orifices which open into a like number of
ductal networks. Confirmation of the number and location of the
ductal orifices can be made by labelling the nipple as described
below.
27. The present invention relies on collecting endogenous ductal
fluids and cellular and non-cellular marker materials from the
individual ductal networks on a duct-by-duct basis. That is, fluids
and marker materials are obtained from a single duct without
obtaining material from any other ducts. This is in contrast to
prior techniques which, in some instances, are able to obtain
cellular and other materials from all milk ducts at once by
applying a mild vacuum to the nipple. It should be noted, however,
that in some instances such screening of all ducts in a single step
may be appropriate in order to identify patients showing
abnormalities for whom further, duct-specific testing according to
the present invention is appropriate.
28. As a first step of the method herein, a location of at least
one duct will be determined, typically by labeling all ductal
orifices as described in co-pending application Ser. No.
08/931,786, the full disclosure of which has previously been
incorporated herein by reference. Briefly, a portion of the
epithelial lining present exposed at the ductal orifice may be
labeled with a visible marker which allows the treating
professional to identify the entry orifice for each of the ductal
networks in the breast. Following identification of the ductal
orifice, a washing fluid will be introduced into the duct in order
to loosen and mobilize cellular material from the ductal lining,
primarily epithelial cells from the lining. The washing fluid is
introduced in an amount and a manner such that substantially the
entire volume of the duct will be washed with the fluid in order to
obtain a sample which is representative of the entire ductal
network. Cellular components from the sample will usually be of the
most interest, but ductal fluids and secreted molecular species
(both small molecules and more usually biological macromolecules
such as proteins and carbohydrates) may also be analyzed. The
washing fluid carrying the cells and other materials is then
collected, and the materials morphologically, histologically,
immunohistologically, chemically, immunologically, enzymatically,
or otherwise examined in order to determine any abnormal or disease
conditions within the ductal network, particularly cancer or a
pre-cancerous condition.
29. In the preferred embodiment, the washing fluid is introduced
using a dual-lumen catheter which permits simultaneous introduction
of the washing fluid and collection of excess washing fluid as it
flushes back outwardly from the ductal network. The fluid being
collected is usually not aspirated (since aspiration could collapse
the duct), and instead the pressure of the introduced fluid is
relied on to both flush the entire ductal network and expel the
excess fluid through the other lumen of the cannula. Optionally,
external pressure may be applied to the breast to enhance or
expedite fluid collection. Typically, the fluid is introduced using
a syringe, with the fluid being introduced at a relatively low
rate, typically in the range from 0.1 ml/sec to 5 ml/sec,
preferably from 0.5 ml/sec to 1 ml/sec. The total introduced volume
of the washing fluid is typically at least 5 ml, typically being in
the range from 5 ml to 25 ml, usually being about 10 ml, and
optionally being greater. A preferred washing fluid is physiologic
saline but contrast media and other physiologically acceptable,
sterile fluids may also be used.
30. An exemplary catheter 50 useful for performing the methods of
the present invention is illustrated in FIGS. 3 and 4. The catheter
comprises a catheter body 52, typically having a length in the
range from 3 cm to 50 cm usually from 10 cm to 25 cm. The catheter
body 52 includes at least a first lumen 54 and a second lumen 56.
The first lumen 54 terminates in a distal port 58, as best seen in
FIG. 4, while the second lumen terminates in a proximally located
port 60, typically being located by a distance d which is
approximately 0.1 cm to 1 cm, usually from 0.1 cm to 0.25 cm,
proximal of the distal port 58. Catheter body 52 will have a
relatively narrow diameter, typically having a maximum diameter in
the dual-lumen region in the range from 0.8 mm to 2.5 mm,
preferably being in the range from 0.8 mm to 1.2 mm. The diameter
of the distal, single-lumen region may be less, as in the range
from 0.5 mm to 1.5 mm, preferably from 0.6 mm to 1 mm. Proximal hub
62 includes a port 64 which is fluidly coupled to the second lumen
56 for delivering the washing fluid into the ductal network. Second
port 66 is provided both for introducing the catheter over a
guidewire and for collecting the washing fluid from the ductal
network via port 58.
31. Referring to FIG. 5, use of the catheter 50 for collecting
marker materials from a ductal network D.sub.2 will be described.
Usually, the ductal network D.sub.2 will first be accessed with a
guidewire, such as a conventional 0.014 inch guidewire(not shown).
After the guidewire is introduced, typically by a distance in the
range from 0.25 cm to 2.5 cm past the orifice O.sub.2, the catheter
50 will be introduced over the guidewire by passing distal port 58
of the first lumen 54 over the external end of the guidewire. The
distal port 58 is introduced into the ductal-network D.sub.2
typically to a depth of about 0.25 cm to 2.5 cm, usually about 0.75
cm to 1.5 cm. As discussed above, the second port 60 will be
located proximally from the first port by a distance in the range
from 0.1 cm to 1 cm, and will thus be closer to the orifice
O.sub.2. After the catheter 50 is in place, the guidewire will
typically be withdrawn and the washing fluid introduced through the
second lumen 56 via port 64 and opening 60. The washing fluid will
flow into the ductal network and will generally reach most of the
ductal volume, typically reaching at least 75% of the ductal
volume, preferably at least 85%, and sometimes as much as 95%.
32. Alternatively, the guidewire and catheter 50 may be introduced
simultaneously, typically with the distal tip of the guidewire
extending a short distance ahead of the distal end of the catheter,
usually about 0.1 cm to 1 cm. The guidewire is used to steer and
the catheter 50 follows to the desired target location in the
duct.
33. The volume of fluid introduced into the ductal network D.sub.2
will be sufficiently large so that substantially the entire volume
of the ductal network may be filled with the washing fluid and
excess fluid will flow from the network as it is displaced by
additional fluid input. Usually, only a small portion in the amount
of washing fluid being introduced will be necessary to fill the
ductal network, usually less than 1 ml, often less than 0.5 ml. The
remaining fluid will continue to be introduced and will thus flush
the cellular and other marker materials from the ductal network
into the opening 58 in the first lumen 54. Thus, that fluid will
pass outwardly through the catheter and may be collected from port
66 in the catheter. Preferably, no vacuum or other aspiration
pressure will be applied to the catheter. Instead, the fluid will
flow outwardly in response to the positive pressure created by the
inflow of washing fluid, optionally with external pressure applied
to the breast.
34. The collected fluid may be treated or analyzed in conventional
ways to identify the presence, amount(s), identities, and/or other
characteristics of any marker materials that may be present in the
collected fluids. For example, cellular materials may be
transferred to a suitable medium, such as RPMI or other growth or
maintenance medium. The cells may then be examined morphologically
under a microscope and/or histologically using suitable
histochemical and immunochemical staining reagents. Chemical and
molecular markers may be identified and/or examined chemically,
immunologically, enzymatically, or by other conventional
techniques. Such analysis techniques are well described in the
art.
35. Kits according to the present invention will comprise at least
a catheter 50 (which may be any dual- or multiple-lumen catheter
capable of accessing an individual ductal network) and instructions
for use (IFU) 80 which are combined together in a conventional
manner, typically within a container 82, which may be in the form
of a pouch, tray, box, tube, or the like. Kits will usually also
include at least a guidewire, and other kit components may also be
provided. For example, a syringe 84 may be provided, usually
pre-filled with saline or other suitable washing medium for washing
the ductal network. Additionally, a collection tray 86 for
receiving and maintaining the cellular material and the washing
fluids collected from the catheter may also be provided.
Optionally, the tray may include a suitable collection medium, such
as RPMI medium. Still further, the kits may include materials for
assaying non-cellular markers as well as components for
identification of the ductal orifice, such as described in
co-pending application Ser. No. 08/931,786, the full disclosure of
which was previously incorporated herein by reference.
36. The following examples are offered by way of illustration, not
by way of limitation.
EXPERIMENTAL
37. A double lumen catheter which would allow a continuous flow of
saline throughout the ductal system was prepared, as illustrated in
FIG. 7. The catheter was a 3 French double lumen catheter with the
proximal lumen smaller in diameter and the distal larger to allow
aspiration. In particular, the catheter 100 had a length from the
hub 102 to the distal tip 104 of 31 cm, an outer diameter of
D.sub.O of 0.041 in, a guidewire lumen D.sub.GW of 0.019 in, and a
crescent-shaped lumen 110. The outer tip diameter D.sub.OT was
0.033 in and the lumenal tip diameter D.sub.LT was 0.017 in,
reflecting a tapered distal end 116. A side port 120 having an oval
geometry of 0.07 in.times.0.016 in formed the distal end of the
lumen 110 and was spaced-proximally of the distal tip by a distance
D.sub.S of 0.16 in. Fluid was introduced through port 130 and lumen
110 out through side port 120 into the ductal lumen. Fluid was
collected through the distal tip and back through the guidewire
lumen (after withdrawing the guidewire), and then through port 140.
Initially the catheter was tested in breasts that had been removed
surgically. Ten breasts were studied and cells were retrieved from
seven. The catheter was also used with twelve anesthetized women
prior to breast surgery. Cells were retrieved from ten of the
twelve (83%). See Table 1.
Materials and Methods
38. After general anesthesia had been administered, the patient's
breast was prepped and draped. Mild suction was applied to the
nipple to try to elicit discharge. A dissecting microscope or loupe
was used to magnify the nipple and identify orifices. A map was
made of the identified orifices. Starting with the most promising
orifice (i.e. most amount of discharge, and/or the largest),
attempts were made to cannulate one or more orifices using either a
standard set of metal dilators (galactography set by Mahan), or a
very small guide wire of the type used in angiography. Once the
duct had been cannulated and dilated to approximately 0.7-1.0 mm,
the double lumen catheter was threaded into the duct. Saline was
instilled, setting up a continuous flow until 10 cc was collected.
The procedure took about 15 minutes. If 10 cc of fluid was not
collected within the 15 minute limit, the procedure stopped
prematurely. The washings were then sent to cytology for
analysis.
Results
39. The results are show in Table 1.
1TABLE 1 patient # breast mass location duct location # duct
pathology cytology Detached breasts 1 R RLQ central 1 Ductal
acellular carcinoma comedo 2 R No cancer 6:00 3 ductal cells L L
breast 9:00, 7:00 3 Micropapillary ductal cells DCIS 3 L LLQ 12:00
3 infiltrating ductal cells ductal carcinoma 4 R RUOQ 8:00 4 DCIS
pagetoid ductal cells 5 L LUOQ 11:00 5 Intraductal ductal cells
carcinoma in situ 6 R no cancer 9:00 2 acellular L 3:00, 9:00 6:00
4 Invasive ductal acellular carcinoma, DCIS 7 L LUOQ 6:00 4
Infiltrating (1) acellular, ductal (2) ductal cells carcinoma, DCIS
8 L LOQ, 3:00 central 2 Infiltrating ductal cells lobular
carcinoma, infiltrating ductal Attached breasts 1 R RUOQ 12:00 2
adeno ca carcinoma cells 2 L retroaerolar central 1 poorly diff,
deteriorated ductal cells carcinoma 3 R RUOQ 3:00 3 tubular
deteriorated carcinoma, cells micropapillary 4 L infraaerolar 9:00
2 invasive ductal deteriorated carcinoma cells 5 R N/A (abscess)
central 1 lactiferous duct Acellular 6 L LUOQ 3-4:00 1 fiberadenoma
Benign mammary epithelial cells 7 R 3:00 fibroadenoma Abund
epithelial cells, benign mammary epithelial cells 8 R 12:00 12:00 2
Invasive ductal Acellular, rare, carcinoma ductal cells 9 R 11:00
11:00 3 Invasive acellular lobular 10 L UOQ central 1 Invasive Mod
lobular macrophage, no ductal cells 11 L LUOQ central 1 Adeno Foam
cells, carcinoma ductal cells 12 R RUOQ 3:00 2 Atyp med Foam cells,
carcinoma rare ductal cells R: right L: left RLQ: right lower
quadrant LLQ: left lower quadrant LUOQ: left upper outer quadrant
LOQ: left outer quadrant RUOQ: right upper outer quadrant UOQ:
upper outer quadrant DCIS: ductal carcinoma in situ
40. While the above is a complete description of the preferred
embodiments of the invention, various alternatives, modifications,
and equivalents may be used. Therefore, the above description
should not be taken as limiting the scope of the invention which is
defined by the appended claims.
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