| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
Radiology Department, St. Joseph's Health Care, 268 Grosvenor St., London,
Ontario N6A 4V2, Canada.
2
Radiology Department, London Health Sciences Centre, University Campus, 339
Windermere Rd., London, Ontario N6A 5A5, Canada.
3
Radiology Department, St. Michael's Hospital, 160 Wellesley St. E., Ontario,
M4Y 1J3, Canada.
Received January 29, 2001;
accepted after revision May 30, 2001.
Address correspondence to D. Taves.
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIALS AND METHODS. We conducted a retrospective review of 232 lesions with indeterminate microcalcifications in 218 women who underwent stereotactically guided breast biopsies. All biopsies were performed using a standard mammography machine with an add-on unit, 121 with conventional and 111 with digital stereotactic guidance. Successful sampling of the lesion was determined by the detection of microcalcifications on specimen radiography or at pathology.
RESULTS. Using the add-on unit, 219 (94.4%) of the 232 targeted lesions were successfully sampled. The size, location, number of cores per lesion, and histology of the lesions were not different between the conventional and digital stereotactic biopsy groups (p > 0.1). Indeterminate microcalcifications were missed on biopsy in nine (7.4%) of 121 cases using conventional radiography and in only four (3.6%) of 111 cases using digital imaging. Digital stereotactic guidance allowed sampling of lesions with fewer calcifications per square centimeter (p < 0.001).
CONCLUSION. Sampling of indeterminate microcalcifications using a standard mammography machine and an add-on unit has a high accuracy, similar to rates reported for dedicated prone biopsy tables. An add-on unit offers the advantage of considerable cost and space savings. Relative to conventional radiography, digital stereotactic guidance allows lesions with fewer calcifications to be sampled and achieves a greater biopsy success rate. Immediate digital images in the biopsy room also permit rapid adjustment of alignment and minimize patient movement.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
An add-on upright stereotactic system and a dedicated prone system were both used in the initial article by Parker et al. [1] that described stereotactic core biopsy. Subsequent work aimed at optimizing stereotactic biopsy has focused predominantly on the use of dedicated prone tables, with only three articles describing the use of add-on units [9,10,11]. In a 1996 survey of United States centers involved in breast imaging, the average number of core biopsies performed per week was 5.7 (range, 0.1-30 core biopsies) [12]. The expense, both in dollars and space, of a dedicated prone stereotactic biopsy system may not be justified for many centers with such a low rate of utilization. A movable add-on stereotactic unit is an excellent alternative, allowing the adaptation of a regular mammography unit for stereotactic biopsy when needed. Patient movement and an increased incidence of vasovagal episodes are the most commonly described disadvantages of add-on units [2, 9,10,11]. Given its practical advantage, further investigation of the accuracy of stereotactic biopsy using an add-on unit is needed.
Stereotactic core biopsy has been performed at our center using a standard mammography machine with an upright add-on unit since 1990. In 1999, the add-on stereotactic system, which used conventional radiography, was replaced with one of the first add-on digital stereotactic units in Canada. This article first evaluates the accuracy of stereotactic biopsy for nonpalpable indeterminate breast microcalcification using an add-on unit and then examines the advantages of digital versus conventional radiographic guidance.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Biopsy Procedure
All biopsies were performed using a DMR regular mammography machine
(General Electric Medical Systems, Milwaukee, WI) with the patient in an
upright seated position. A Stereotix 2 conventional add-on unit (General
Electric Medical Systems) was used before May 1999, and a Seno Vision digital
add-on unit (General Electric Medical Systems) was used after May 1999.
Biopsies were performed by three radiologists who specialize in breast
imaging. A 14-gauge needle was used in all but five biopsies (when a 16-gauge
needle was used), with sampling throws of 22 mm in most patients.
For conventional stereotactic core biopsies, the procedure is explained to the patient, who is then positioned for scout images. Multiple attempts (one to eight) are often needed to center the target microcalcifications in the scout image and to optimize the radiographic technique for the perception of microcalcifications. Once the targeted microcalcifications are located, the compression is tightened and a two-on-one stereotactic image of the lesion is obtained. The target is identified on both stereotactic images, and a core biopsy pattern is selected. The coordinates for each core are determined from the stereoboard. The biopsy unit is zeroed manually by the technologist while the skin over the lesion is cleaned and anesthetized. The patient is then given an opportunity to hear the biopsy gun discharge. The core biopsy needle is inserted into the holder and through the skin at the zero location, and prebiopsy stereotactic images are taken to confirm the needle position. The prebiopsy images are used to ensure that the patient has not moved during preparation and freezing. Any change in target position as a result of patient movement is measured with a ruler, and the coordinates of each core in the biopsy pattern are adjusted. Next, the needle is placed in a biopsy gun (C. R. Bard, Covington, GA) and the series of biopsies are taken in the preselected pattern by adjusting the x, y, and z coordinates of the needle holder for each core. After the sample has been obtained, the patient is released from compression, the add-on arm is removed, and the tissue sample is radiographed at three different exposures (22, 23, and 24 kVp) using the mammography machine. Post-biopsy images of the breast were not routinely obtained with the conventional add-on unit.
The main advantage of the digital add-on unit is that the scout, stereotactic, prebiopsy, and sample radiographs are all obtained with the digital cassette and can be viewed within 15 sec on the display terminal located in the biopsy room. This procedure is in marked contrast to the conventional add-on unit. With the conventional unit, each of the radiographs—approximately seven per biopsy: four scout images, one stereotactic image, one needle position prebiopsy stereotactic image, and one sample radiograph—is developed in a separate room, a process requiring approximately 3 min for each image.
The digital add-on unit consists of a charge-coupled device with a 6 x 6 cm field of view incorporated into an 18 x 24 cm cassette that fits into the cassette holder of the regular mammography machine. A parallel fiberoptic connection relays the image directly from the digital cassette to the workstation. The workstation has computerized target and core biopsy pattern selection and a computerized ruler to assist with needle placement and adjustments. The digital add-on unit also has a motorized, automated needle positioner that is integrated with the workstation to facilitate biopsy planning and execution.
The procedure for the digital add-on unit follows a sequence similar to the conventional technique with only a few altered steps. The ability to magnify images, change the window and level settings of the digital display, and invert the image (black on white) decreases the number of scout images required by allowing the detection of fainter microcalcifications without a change in radiographic technique. The 12-fold reduction in time for "developing" digital images allows the biopsy needle to be realigned more than once if necessary before biopsy and permits post-biopsy images of the sampled lesion to confirm removal of microcalcifications while the patient is still in position. Even with the digital add-on unit, postbiopsy images of the breast are not routinely obtained at our center. Only one exposure of the biopsy sample is necessary with the digital add-on unit because the image can be manipulated on the computer monitor to allow optimal viewing of microcalcifications.
Pathology and Management Algorithm
Accurate sampling of the targeted lesion was defined as retrieval of
calcifications at specimen radiography or pathology
[6,
4,
13,
14]. A pathologist examined
all samples, and the presence or absence of microcalcification was reported
for each biopsy. If no calcifications were retrieved, a second core biopsy or
surgical excision was offered to the patient
[4,
6,
13,
15,
16].
Invasive malignancy or ductal carcinoma in situ diagnosed at core biopsy was considered malignant and resulted in surgical excision. When the biopsy result is atypical ductal hyperplasia, surgical excision is also recommended at our center because of the 11-58% reported rate of underestimation of malignancy [16,17,18,19,20,21]. The clinical significance of biopsies yielding lobular carcinoma in situ, atypical lobular hyperplasia, and papillary lesions is controversial [20], and some researchers agree stereotactic core biopsy might underestimate the actual lesion pathology. The reported rates of carcinoma at surgical excision after stereotactic core biopsy are 0-17% for papillary lesions, 0-50% for atypical lobular hyperplasia, and 9-34% for lobular carcinoma in situ [20, 22]. At our center, these indeterminate lesions are referred for surgical excision. Excision is also recommended for any lesion for which the core biopsy pathology results do not correspond with the mammographic findings [6, 9, 16, 19]. All other pathology results are considered benign, and the patient undergoes follow-up mammography at 6 or 12 months at the discretion of the biopsy radiologist [2, 10].
Mammography Measurements
Characteristics of each lesion were reviewed retrospectively on the basis
of the original mammographic images. Mean diameter, number of
microcalcifications, location of the lesion, number of cores per biopsy, and
pathology diagnosis were recorded for lesions in the conventional film and the
digital groups. The mean diameter was calculated on the basis of the longest
axis in each of the non-magnified orthogonal images
[5]. No lesions were excluded
on the basis of size. For the purpose of analysis, lesions were grouped
according to size in the following categories: less than 5 mm, 5-10 mm, 11-15
mm, 16-20 mm, and greater than 20 mm
[5]. The number of
microcalcifications per lesion
[6] was recorded as (per square
centimeter) less than five, six to 15, 16-30, or more than 30. The total
number of microcalcifications per square centimeter was calculated by placing
a 1-cm2 hole over the most densely calcified part of the lesion
[23]. Finally, we noted the
quadrant in which each lesion was located.
Statistics
The overall accuracy of the add-on unit was calculated from the combined
data from both add-on units. The overall sensitivity and specificity of the
add-on units were calculated on the basis of whether the core biopsy provided
pathology results that prompted the appropriate management of the lesion:
excision versus follow-up [5,
14]. Core biopsies yielding
indeterminate pathology results (atypical ductal hyperplasia, lobular
carcinoma in situ, atypical lobular hyperplasia, or a papillary lesion) were
considered true-positive if excisional pathology results corresponded to the
core biopsy or showed malignancy (ductal carcinoma in situ, invasive ductal
carcinoma, or invasive lobular carcinoma) and false-positive if excisional
pathology results were benign. The overall data were also analyzed to
determine if any one of the studied lesion characteristics predisposed to
unsuccessful biopsy. The digital and conventional radiography groups were then
compared with one another to determine if any of the baseline characteristics
were different between the two groups. Variables analyzed included lesion
size, lesion location, number of calcifications, number of cores per biopsy,
and lesion pathology results. The variables were analyzed using a chi-square
test with a 95% confidence interval.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Microcalcifications were confirmed at specimen radiography or biopsy pathology in 219 (94.4%) of 232 cases. Microcalcifications were seen at specimen radiography alone in 206 (91.2%) of 226 cases. In six cases for which the conventional film add-on unit was used, the specimen radiographs were no longer available for confirmation.
Frank malignancy was diagnosed on core biopsy in 43 lesions (18.5%). These lesions included 36 cases of ductal carcinoma in situ, six cases of invasive ductal carcinoma, and one case of lobular carcinoma. At surgery, malignancy was confirmed in all but one case. One case of high-grade ductal carcinoma in situ with comedo necrosis at core biopsy did not show malignancy at excision. This occurrence has been described in previous reports [5, 10] and likely represents a case in which the lesion was completely removed at biopsy or was missed at mastectomy rather than an actual false-positive result. For the purpose of this report, however, it was considered a false-positive. The pathology result of seven lesions (3.0%) was "suspicious for malignancy." Surgical biopsy confirmed malignancy in six of these lesions and atypical lobular hyperplasia in the seventh. Nine lesions were indeterminate at core biopsy. Eight (3.5%) of these represented atypical ductal hyperplasia at core biopsy and one (0.4%) was an indeterminate papillary lesion. Seven of these were excised and four represented benign lesions (including the papillary lesion) and two represented ductal carcinoma in situ and one atypical lobular hyperplasia. Despite recommendations for further investigation, the remaining two patients declined surgical excision and mammographic surveillance.
For 162 lesions (69.8%), a benign diagnosis was reported for the core biopsy specimen. Three patients requested surgical biopsy, and benign findings were surgically confirmed. Two patients underwent excisional biopsy because sonographically guided biopsy results of nearby breast lesions were positive for ductal carcinoma in situ. Three patients who had benign pathology results on core biopsy underwent surgical biopsy because of incongruity between biopsy results and mammographic appearance. One patient had benign disease at surgical biopsy, one had invasive ductal carcinoma, and the third had ductal carcinoma in situ. These last two cases were false-negative results. Ninety-eight of the 154 remaining bening lesions (63.6%) had follow-up mammography with no evidence of malignancy, seven patients declined follow-up mammography, and 52 patients had not yet completed their mammographic follow-ups that were scheduled at 6 months to 1 year after their biopsy.
For 13 biopsies (5.6%), no calcifications were harvested. A correct pathologic diagnosis of malignancy was obtained in two of these patients. Two lesions underwent core biopsy twice, and calcifications were lacking on specimen radiography and pathology both times. These lesions were both benign at open biopsy. Two patients who did not have microcalcifications harvested at stereotactic core biopsy refused surgical excision and follow-up.
Excluding the 11 patients who refused follow-up (two with atypical ductal hyperplasia, seven with benign pathology findings, and two with no microcalcifications sampled), the sensitivity and specificity for stereotactic core biopsy using an add-on unit in our series are 94.5% and 97.0%, respectively.
Stereotactic core biopsy was complicated by minor bleeding in three cases (1.3%) and vasovagal episodes in two cases (0.9%). In three of these five patients the biopsy was terminated early, but microcalcifications were successfully harvested from four of the five lesions.
The mean number of passes performed through each lesion was 10.1 (range, 3-24 passes). The mean length of the long axis of the 229 lesions for which original mammograms were available was 13.9 mm for successful biopsies and 16.4 mm for unsuccessful biopsies, but the difference was not statistically significant (p > 0.1). No single quadrant resulted in fewer successful biopsies (p > 0.1). The number of cores per lesion and the number of microcalcifications per square centimeter did not influence the likelihood of a successful biopsy (p > 0.1).
Comparison of Add-On Units with Conventional and Digital
Guidance
Microcalcifications were confirmed on specimen radiography or biopsy
pathology in 112 (92.6%) of 121 lesions for the conventional radiography group
and 107 (96.4%) of 111 lesions for the digital group (p > 0.1)
(Table 1). For the presence of
microcalcifications at specimen radiography only, the accuracies were 87% and
95.5%, respectively (p < 0.05). The distribution of lesion
pathology (frank malignancy, suspicious for malignancy, indeterminate, benign
lesion, and lesion not sampled) was the same for the two groups (p
> 0.1). Open biopsy was avoided in 78 patients (69.6%) in the conventional
radiography group and 78 (73.6%) in the digital group. The number of core
biopsies performed for each lesion was recorded in 77 cases (63.6%) for the
conventional radiography group and 85 (76.6%) for the digital group. No
difference was seen in the number of passes per lesion, with a mean of 10.6
passes for the conventional radiography group and 9.8 for the digital group
(p > 0.1). The mean length of the lesions was 14 mm (15.2 mm for
the conventional radiography group and 12.7 mm for the digital group; range,
2.5-110 mm), but the difference was not statistically significant (p
> 0.1). The location of lesions in the breast had similar distributions
(p > 0.1) in the digital and conventional radiography groups, with
most lesions (47.4%) being located in the upper outer quadrant. The lesions in
the two groups differed significantly in the number of calcifications per
square centimeter. Lesions in the digital group had fewer calcifications than
those in the conventional radiography group (p < 0.001)
(Table 2).
|
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The add-on unit offers three distinct advantages over the prone table. The first is that the mammography machine can be used to obtain standard mammographic images when not being used in conjunction with the add-on unit. A single technologist can convert between the biopsy setup and regular mammography in less than a minute. This feature can be particularly useful and efficient when full-sized scout images or magnification images are needed before the biopsy. The second benefit is that the add-on unit is less expensive than a prone table, an advantage that may be attractive to small- and medium-sized centers that perform fewer stereotactic biopsy procedures. The digital add-on unit costs approximately $125,000 (Canadian), whereas a dedicated prone unit costs approximately $350,000 (Canadian). At an average United States center performing five biopsies every week, each biopsy done with the prone unit would cost $87 (Canadian) more than with an add-on unit, considering only the difference in machine price, if the machine is used more than 10 years. If 30 biopsies are performed each week at the busiest United States centers, the cost difference is only $14 (Canadian) per biopsy (Fig. 1). The third advantage of the add-on unit is that it saves space because it does not require a separate installation.
|
Previous articles have described frequent vasovagal episodes as one of the main disadvantages of the add-on unit [2, 9,10,11, 27]. The rate of vasovagal episodes in our series was two (0.9%) of 218 patients. We minimized the number of vasovagal episodes by explaining the procedure to the patient, allowing the patient to hear the biopsy gun sound before the biopsy, having the patient closely supervised by a technologist throughout the procedure, and having the patient drink juice before the procedure to maintain her blood glucose. Similarly, Caines et al. [9] described four vasovagal episodes for the first 125 patients who underwent stereotactic core biopsy in the upright position with their add-on unit. With experience, those authors were able to minimize vasovagal episodes so that none of their subsequent 129 patients was affected (1.6% overall). Doyle et al. [10] described a 29% vasovagal rate, and Welle and Clark [11] described a 38% vasovagal rate with patients in the upright position. The frequency of vasovagal episodes in these reports may be elevated because of lack of experience—only 14 patients and eight patients, respectively, were biopsied in the upright position. These centers did continue to use the add-on units but preferentially performed biopsies with patients in the decubitus position, thus completely eliminating vasovagal episodes. Unfortunately, some lesions are not adequately seen with the patient in the decubitus position. In these reports, and in our experience, all lesions were visible and accessible for biopsy in the upright position [2, 9,10,11, 27].
The use of prone units has been advocated over the use of add-on units because the prone position is thought to minimize patient movement [10]. Patient movement was a factor for a small number of the misses in the first half of our series as well as in the series of Caines et al. [9], who used an add-on unit with the patient sitting upright. Using the add-on unit with the patient decubitus might eliminate this problem. Parker and Burbank [2] suggested that time was an important factor in unwanted patient movement. Until now, the prone units had the advantage of offering digital guidance, thus decreasing the length of time required to perform a biopsy by eliminating many steps. The new digital add-on unit offers the same advantages. None of the instances in which lesions were missed with the digital add-on unit was attributed to patient movement. With the conventional add-on units, 20-50 min per procedure has been reported [9,10,11], whereas biopsies with the prone digital units require 15-20 min [4]. In our experience, changing from the conventional add-on unit to the digital add-on unit decreased the procedure time by half, from approximately 50 to 20 min (breast compression to specimen radiography). Most of the time savings is from the speed of displaying digital images (15 sec per image) rather than developing radiographs (3 min per image).
Our analysis suggests that no one lesion characteristic was associated with an increased risk of unsuccessful biopsy. Our findings are in agreement with two reports in which the size of the lesion [5, 6] and the number of calcifications per lesion [6] were independent of biopsy success. To our knowledge, only one study has suggested that small lesions are more often missed at stereotactic biopsy [18].
When the conventional add-on unit was replaced with the digital unit, the number of lesions missed at stereotactically guided biopsy decreased from 7.4% to 3.6% for the detection of microcalcifications at sample radiography or pathology. The number of lesions missed decreased from 13% to 4.5% if only the detection of microcalcifications at sample radiography is considered, which is a statistically significant improvement of the digital over the conventional add-on unit. Although lesion size, location in the breast, and histology of the lesions were similar, the cases sampled with the digital unit were composed of lesions with fewer calcifications per square centimeter. Increased operator experience, shortened biopsy time, postbiopsy images, and differences between conventional radiographic and digital images may contribute to the difference in successful lesion sampling between conventional and digital add-on units.
A trend toward increased accuracy with more biopsy experience has been shown by Brenner et al. [7], who reported that the accuracy for early biopsy experience was 92% compared with 97% for later experience. For the first half of the lesions sampled with conventional stereotactic guidance (60 lesions) in our series, the accuracy was 91.7%; and for the second half (60 lesions), the accuracy was similar at 93.3%. Although improved ability resulting from increased experience may account for some of the change in accuracy, it is unlikely to completely explain the difference observed in our study.
With the digital unit, the time the patient is asked to remain stationary with the breast in compression is decreased by more than half. This probably contributes to a greater biopsy success rate for the digital add-on unit by minimizing patient and therefore target microcalcification movement [2, 10].
At our center, sample radiography is performed with the mammography machine and cannot be performed until the patient has been removed from compression. Therefore, successful sampling of microcalcifications is not confirmed until all samples have been harvested. Postbiopsy images are not routinely obtained for conventional or digitally guided stereotactic core biopsy at our center. However, the ease and speed of acquiring post-biopsy images with the digital unit give the radiologist the opportunity to confirm lesion sampling by comparing pre- and postbiopsy images before moving the patient. This advantage of the digital system likely contributed to improved accuracy, and probably allowed lesions with fewer microcalcifications to be targeted and successfully sampled.
The line pair resolution of the Stereotix 2 conventional film add-on unit is 16-20 line pairs per millimeter, depending on the quality of film used. For the Seno Vision digital add-on unit, the resolution is only 12 line pairs per millimeter. The ability of the Seno Vision to depict breast lesions and microcalcifications in particular is made comparable if not superior to conventional radiography by its increased dynamic range. The increased dynamic range includes image magnification of as much as four times and control of image contrast through window and level settings. Better perception of microcalcifications through magnification of images, image contrast adjustment, or inversion of the image could contribute to more accurate targeting of lesion and the ability to correctly target lesions with fewer microcalcifications (Fig. 2A,2B,2C,2D). This finding corresponds to our early clinical experience, in which a subset of lesions with few and faint microcalcifications was not triaged for stereotactic biopsy because they would not be detectable on conventional stereotactic images. The digital add-on unit now allows sampling of any lesion that can be seen on a regular mammogram and characterized on magnification images.
|
|
|
|
Mammographic assessment of microcalcifications is more difficult than for masses [28]; therefore, many microcalcifications will be considered indeterminate and scheduled for core biopsy. An add-on stereotactic biopsy unit is an excellent alternative to a dedicated prone unit. The accuracy of the add-on and prone units is similar, but the add-on unit is less expensive and is combined with a regular mammography machine, thus saving space and reducing initial and replacement capital costs. In our experience, vasovagal episodes and increased patient movement were not problematic; and others have shown that these concerns can be virtually eliminated by using the add-on unit with the patient in the decubitus position. Replacing the conventional add-on unit with a digital unit has shortened the length of the procedure, which decreases patient discomfort by minimizing the amount of time she undergoes breast compression. The digital unit's shorter procedure time also reduces patient movement, likely contributing to improved accuracy. With the digital unit, target images can be magnified and contrast can be adjusted, allowing lesions with fewer microcalcifications per square centimeter to be targeted and achieving a greater biopsy success rate than the conventional add-on unit.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K Faulkner, S McCormack, and K Bennison A retrospective analysis of digital stereotaxis in breast screening Br. J. Radiol., July 1, 2007; 80(955): 563 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Koskela, M. Sudah, M. H. Berg, V. J. Karja, P. K. Mustonen, V. Kataja, and R. S. Vanninen Add-on Device for Stereotactic Core-Needle Breast Biopsy: How Many Biopsy Specimens Are Needed for a Reliable Diagnosis? Radiology, September 1, 2005; 236(3): 801 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Yang, G. J. Whitman, M. M. Johnson, M. Bolanos-Clark, A. C. Kushwaha, K. K. Hunt, and P. J. Dempsey Needle Localization for Excisional Biopsy of Breast Lesions: Comparison of Effect of Use of Full-Field Digital versus Screen-Film Mammographic Guidance on Procedure Time Radiology, April 1, 2004; 231(1): 277 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Kirshenbaum, T. Voruganti, C. Overbeeke, M. D. Kirshenbaum, P. Patel, G. Kaplan, V. Maker, C. August, and R. P. Cavallino Stereotactic Core Needle Biopsy of Nonpalpable Breast Lesions Using a Conventional Mammography Unit with an Add-On Device Am. J. Roentgenol., August 1, 2003; 181(2): 527 - 531. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
