Confocal Microscopy of Unfixed Breast Needle Core Biopsies: A Comparison to Fixed and Stained Sections

Linda M Schiffhauer
Department of Pathology and Laboratory Medicine
Medical Center
University of Rochester
601 Elmwood AvenueBox 62614642RochesterNYUSA

J Neil Boger
Lucid, Inc
Henrietta Town Line Road
2320, 14623Brighton, RochesterNYUSA

Thomas A Bonfiglio
Department of Pathology and Laboratory Medicine
Rochester General Hospital
1425 Portland Avenue14621RochesterNYUSA

Medical Center
University of Rochester
601 Elmwood AvenueBox 62614642RochesterNYUSA

James M Zavislan email@example.com
The Institute of Optics
University of Rochester
Wilmot 31714642RochesterNYUSA

Margarita Zuley firstname.lastname@example.com
The Elizabeth Wende Breast Clinic
170 Sawgrass Drive14620RochesterNYUSA

Magee-Women's Hospital of UPMC
300 Halket Street15213PittsburghPAUSA

Christi Alessi Fox
Lucid, Inc
Henrietta Town Line Road
2320, 14623Brighton, RochesterNYUSA

BMC Cancer

Confocal Microscopy of Unfixed Breast Needle Core Biopsies: A Comparison to Fixed and Stained Sections
10.1186/1471-2407-9-265BioMed Central Page 1 of 10 (page number not for citation purposes) Research article * Corresponding author
Background: Needle core biopsy, often in conjunction with ultrasonic or stereotactic guided techniques, is frequently used to diagnose breast carcinoma in women. Confocal scanning laser microscopy (CSLM) is a technology that provides real-time digital images of tissues with cellular resolution. This paper reports the progress in developing techniques to rapidly screen needle core breast biopsy and surgical specimens at the point of care. CSLM requires minimal tissue processing and has the potential to reduce the time from excision to diagnosis. Following imaging, specimens can still be submitted for standard histopathological preparation.Methods: Needle core breast specimens from 49 patients were imaged at the time of biopsy. These lesions had been characterized under the Breast Imaging Reporting And Data System (BI-RADS) as category 3, 4 or 5. The core biopsies were imaged with the CSLM before fixation. Samples were treated with 5% citric acid and glycerin USP to enhance nuclear visibility in the reflectance confocal images. Immediately following imaging, the specimens were fixed in buffered formalin and submitted for histological processing and pathological diagnosis. CSLM images were then compared to the standard histology.Results:The pathologic diagnoses by standard histology were 7 invasive ductal carcinomas, 2 invasive lobular carcinomas, 3 ductal carcinomas in-situ (CIS), 21 fibrocystic changes/proliferative conditions, 9 fibroadenomas, and 5 other/benign; two were excluded due to imaging difficulties. Morphologic and cellular features of benign and cancerous lesions were identified in the confocal images and were comparable to standard histologic sections of the same tissue.Conclusion: CSLM is a technique with the potential to screen needle core biopsy specimens in real-time. The confocal images contained sufficient information to identify stromal reactions such as fibrosis and cellular proliferations such as intra-ductal and infiltrating carcinoma, and were comparable to standard histologic sections of the same tissue. Morphologic and cellular features of benign and cancerous lesions were identified in the confocal images. Additional studies are needed to 1.) establish correlation of the confocal and traditional histologic images for the various diseases of the breast; 2.) validate diagnostic use of CSLM and; 3.) further define features of borderline lesions such as well-differentiated ductal CIS vs. atypical hyperplasia.

Background

The "Gold Standard" for diagnosis of breast disease is tissue biopsy followed by histological processing and pathologic diagnosis. A frequently used method to perform a breast biopsy is needle core biopsy, which is less invasive than surgical biopsy and allows tissue to be removed from the breast with minimal scarring and no deformity of the breast. The procedure generally produces a specimen 1-3 mm in diameter and 0.3-2 cm long depending on the nature of the lesion. The specimens are fixed in buffered formalin and submitted for histological processing and evaluation. Specimen adequacy can be assessed in a limited fashion by radiographing the specimen core biopsies to verify removal of calcifications, if calcifications were the finding being targeted for sampling. However, specimen adequacy cannot accurately be confirmed at the time of biopsy and must await histologic examination. Further, if there are no calcifications in the targeted area, no specimen imaging is routinely done at the time of core biopsy. Potentially, this delay in determining specimen adequacy could be mitigated with the use of confocal scanning laser microscopy (CSLM). In addition, CSLM could provide the clinician with a preliminary screening diagnosis within minutes and permit immediate re-biopsy at the point of care, if necessary.

Reflectance CSLM is an optical imaging technique that provides digital images of nuclear and cellular morphology of tissue [1]. It utilizes optical sectioning to form an image of a single horizontal plane either on the surface of the sample or within the sample to a depth of 300 μm. The image records the light backscattered from intra-and inter-cellular constituents within the tissue. The technology has been used non-invasively in human skin in-vivo, producing 3-5 μm thick horizontal sections and a lateral resolution of 0.5-1.0 μm, which compares favorably with the typical 5 μm thick sections prepared for conventional histology. The technique has been applied intra-operatively for the assessment of parathyroid glands, as an exvivo application in several studies involving Mohs micrographic surgery and the use of contrast agents, and in pilot studies of ex-vivo hepatic and pancreatic tissues [2][3][4][5][6][7][8].

Reflectance confocal imaging has also been applied to imaging of breast cancer in mouse and human models [9][10][11].

Confocal imaging of breast needle core biopsies for pathological examination prior to standard histopathology can be accomplished with minimal processing of the tissue and no tissue damage in a fashion identical to published reports for CSLM of ex-vivo skin specimens [12]. Because the images represent the spacial variation of optical backscatter within the tissue, contrast agents such as acetic acid or citric acid can be used to enhance the optical contrast of the nucleus relative to the extra-cellular struc-tures such as collagen [13]. In this study, we used CSLM to image breast needle core biopsy specimens, representing a range of breast conditions, during a patient's visit at a radiology practice specializing in breast care, and created a representative set of confocal images with comparative histology.

Methods

Forty-nine patients underwent needle core biopsy between August 2001 and January 2002 at a large, freestanding breast diagnostic clinic (Elizabeth Wende Breast Clinic, Rochester, NY). This study has been reviewed and approved by an Institutional Review Board (IRB) at the University of Rochester Medical Center, Rochester, NY. The confocal imaging was performed at the clinic at the time of biopsy. Based on radiologist examination, the lesions were characterized using the Breast Imaging Reporting And Data System (BI-RADS). Biopsied cases were assigned as either category 4 or 5. Lesions in category 4 are defined as a suspicious abnormality, and lesions in category 5 as highly suggestive of malignancy. One category 3 case was also biopsied and submitted for imaging during this study. Category 3 is defined in BI-RADS as probably a benign finding.

The confocal microscope used in this study was the commercially available VivaScope 2000 (Lucid, Inc., Rochester, NY), designed specifically for imaging freshly excised surgical tissues. Details of the optical design of the confocal microscope used in this study have been published previously [14]. The system includes a diode laser illumination at a wavelength of 830 nm, maximum illumination power of 30 mW and a 30×, 0.9 numerical aperture water immersion objective lens. The lateral resolution with the 30× objective lens was 1 μm, and the vertical (axial) resolution was < 5 μm. The maximum depth of imaging was approximately 300 μm.

Core biopsies were acquired using either a vacuumassisted or non vacuum-assisted biopsy devices (11-gauge Mammotome, Ethicon Endosurgery, NJ, 14-gauge Tru-Cut, Baxter Healthcare, CA, 14-gauge Bard, AZ). The gauge of the needle was selected by the radiologist. The freshly excised needle core specimen contained 2-7 (an average of 4.1) pieces of tissue. They were radiographed to identify the pieces that contained calcium, and the piece with the highest density of calcium was selected for imaging. If the specimen did not contain calcium, the piece with the least amount of fat was selected for imaging. The remaining pieces were immediately fixed in formalin. Specimens were excluded from the study if they contained only one piece of tissue so that there would be no potential risk to standard histological processing and subsequent pathological diagnosis. Samples used in this study were fixed in formalin within 20 minutes of removal.

In this study we used two contrast agents, a 5% citric acid solution and glycerin USP. Samples treated with these contrast agents show enhanced nuclear detail and reduced stromal reflectance. The 5% citric acid affects the nuclear reflectance in the same way as 5% acetic acid does, causing compaction of the chromatin, increasing the backscattered light and making the nuclei appear bright in confocal images. The refractive index of glycerin matches that of collagen, reducing its reflectance. Non-adipose stromal areas in the core biopsy specimens treated with glycerin typically became completely translucent and facilitated the ability to image into the specimen.

Core specimens were submerged in a 5 ml fresh solution of 5% citric acid by mixing 2.5 ml of 10% citric acid and 2.5 ml of 0.9% sodium chloride irrigation solution (saline) for 30 seconds. The specimen was then removed from the solution, placed with a drop of glycerin in a tissue cassette and encapsulated with a second adhesive window that stabilized the tissue and prevented drying. The cassette was photographed and placed on the tissue stage of the microscope. The tissue was brought into focus, the laser power was adjusted for optimal image quality, and a composite mapping sequence was initiated. The composite map is a series of full field (475 × 475 μm) images in a single, horizontal plane that are automatically captured and "stitched" together to form a composite image that ranged from 4 × 4 mm to 12 × 12 mm square. This mosaic of images "cuts" an optical section into the specimen close to its surface. Areas of interest were identified and realtime imaging was performed in a 475 × 475 μm field. In areas of interest, a stack of 16 images was captured within the tissue, with each sequential image corresponding to a 3.175 μm step deeper into the tissue. The thickness of a single 16-image stack was approximately 50.4 μm. Sequential stacks of images were captured as long as image quality and resolution were maintained, to a maximum depth of 300 μm. Individual full field images were captured as needed. The complete imaging process took 10-20 minutes, although initial images were obtained in less than five minutes. Following imaging the tissue piece was fixed in buffered formalin along with the rest of the specimen and submitted for standard histological processing (Rochester General Hospital). The unaltered confocal images were reviewed and comparable photomicrographs of the histology were taken.

To evaluate the influences of the contrast agents on immunohistochemical staining, we undertook an IRB-approved (University of Rochester Medical Center) compatibility study on waste mastectomy tissue to examine the effect of different combinations of 10% citric acid, 10% buffered citric acid, 5% acetic acid, glycerin USP, and a saline bath on ER/PR and HER-2/nu stains. The intent of the study was to test the effects of citric acid and acetic acid at the same molarity on breast tissue. The citric acid was buffered with 0.803 M sodium citrate to a pH of 2.4, to match the pH of 5% acetic acid and closely match its molarity of 0.839 M. We compared the appearance of immunohistochemical stains on specimens that were treated with contrast agents to control specimens that were untreated. Following treatment, all specimens were fixed in buffered formalin, submitted for standard histologic processing (University of Rochester Medical Center), and submitted for ER/PR staining, and HER-2/nu staining if cancer was suspected. Pathologists reviewed the sections and stained tissues for artifacts and immunological staining effects outside that typically seen.

Results

Needle core biopsy specimens were imaged from 49 patients whose breast lesions had been categorized as BI-RADS 3, 4 or 5. The pathologic diagnoses from standard histology were 7 invasive ductal carcinomas, 2 invasive lobular carcinomas, 3 ductal carcinomas in-situ, 21 fibrocystic changes/proliferative conditions, 9 fibroadenomas, 5 other/benign; two were excluded due to imaging difficulties.

Confocal images comparable to standard pathological sections were taken from the same piece of tissue, but not necessarily of the identical field because of differing tissue orientation and sectioning depth. Samples treated with 5% citric acid solution and glycerin showed enhanced nuclear detail and reduced stromal reflectance. The confocal images taken from the needle core biopsy samples showed a range of morphologic features associated with benign and cancerous lesions when reviewed by the three pathologists. Radiological and H&E data from 7 cases are shown (Table 1) The results of the compatibility study (Table 2) indicated that in samples of specimen 7, which was ER positive, a solution with a pH ≤ 2.4 induced a false negative ER stain ( Figure 7B, C). In specimen 1, which was PR control positive, a solution with a pH < 2.4 induced a false negative PR stain. Glycerin USP was not found to have any effect on either ER/PR or HER-2/nu staining. None of the agents induced a false positive or negative HER-2/nu stain. Hematoxylin and eosin staining was not affected by any of the preparations.

Discussion

The results of the breast needle core study confirm that confocal images can be safely obtained without compromising the ability to make a diagnosis by standard histopathologic preparation. The compatibility study indicated that current immunohistochemical stains are not affected by citric acid or acetic acid if the pH of the contrast agents is buffered to ph>2.4 and the samples are bathed in saline prior to fixation. Also, this study illustrates that CSLM can image features important in the differential diagnosis of breast disease from a range of patients that are presenting for a percutaneous needle core biopsy. However, this study was not structured to determine the sensitivity and specificity of confocal diagnostic criteria. The three pathologists that reviewed the confocal images were aware of the diagnoses from the histologically prepared specimens and were able to view the case slides while viewing the images. Overall, when viewing the breast tissue using confocal imaging, the architectural and cytologic features characteristic of each diagnosis were analogous to those seen using standard histologic processing. The diagnosis most easily made was distinguishing invasive carcinoma from benign tissue. The architectural patterns of invasion characteristic of both invasive ductal and lobular carcinoma were easily seen. Fibrosis was distinguished without difficulty from invasive carcinoma by cellularity, morphology of the nuclei, and the relationship of the nuclei to each other. For normal breast tissue, the architecture of ducts, terminal ducts and acini was clearly visible and benign alterations of these structures such as cysts, apocrine metaplasia and  fibroadenomas were obvious. Intraductal proliferations, such as usual ductal hyperplasia and ductal carcinoma in situ, showed architectural and cytologic features in confocal imaging equivalent to those seen using standard histology. Limitations that are typically encountered in standard histology, such as distinguishing atypical proliferations and low grade ductal carcinoma in situ, are expected in confocal imaging as well. One challenge for confocal imaging is viewing specimens composed predominantly of fatty tissue; however, most clinically significant lesions are not expected to be associated primarily with fat.

There are three principal technical challenges in imaging needle-core breast specimens with CSLM. The first is the limited sampling of the tissue. The second is the heterogeneous nature of breast tissue. The third is limited reflectance contrast of the epithelial tissue.

Sampling

The volume of tissue imaged precluded the ability to completely screen the specimen. Only one mosaic was taken, and from this mosaic multiple image stacks of suspicious regions were acquired. This was due to limitations in the imaging speed of the system and the protocol require- ments to fix the tissue within 20 minutes. Because of the limited sampling, frank cancers were often easily seen, but localized ductal carcinoma in situ could be overlooked. Sampling can be improved through enhancements in hardware and software. In this study the mosaic was taken over a square region that circumscribed the tissue, but much of the imaged area did not contain tissue. New versions of the software application allow for the collection of a 10 × 10 mm color macroscopic photo. From this macroscopic photo, the operation can direct the collection of imaged mosaics and stacks. Also, the tissue cassette that held the specimens did not orient the specimen in a particular direction. Using a specifically designed carrier that would orient the specimens lengthwise, the imaging time could be reduced by aligning the tissue with the mechanical motion. The system used in the study imaged 0.475 × Ductal carcinoma in situ, nuclear grade 2 0.475 mm at 9 frames per second, or 2.0 mm 2 per second. A core specimen 1.5 mm in diameter and 10 mm in length aligned in a carrier could be imaged at four depths with a fully optimized system in less than two minutes.

Fibrocystic changes

Heterogeneous nature of breast tissue

The depth of imaging (less than 0.3 mm) of the confocal microscope is a limitation for large specimens in that it allows for examination near the surface only. This depth limitation is related to refractive index inhomogeneity of the tissue and the large numerical aperture (0.9) of the imaging system. Of the three main types of tissue in the breast, the adipose tissue limits imaging depth the most. The refractive index of human mesenteric adipose tissue is 1.467 versus 1.41 for the surrounding collagen [15]. This refractive difference induces large optical abberations when attempting to image through a single layer of adipose tissue. Imaging of epithelium in collagen is possible since, as noted earlier, collagen regions of the core biopsy were translucent after treatment with glycerin due to the Infiltrating lobular carcinoma, nuclear grade 2 Figure 6 Infiltrating lobular carcinoma, nuclear grade 2. Small malignant cells are infiltrating the breast tissue in single file arrangements (arrows) and small nests in images A and B. Nuclear pleomorphism is shown.

Poorly differentiated infiltrating ductal carcinoma, nuclear grade 3 index matching of glycerin. The index matching reduces both scattering and image abberations. Ducts and glands could be seen visually as pale white structures inside the translucent specimens. The visibility of epithelial structures is believed to be from enhanced backscatter/acetowhitening of the cellular tissues. Thus, epithelial regions appeared as bright areas in the mosaic, whereas, the glycerin-perfused fibrous tissue appeared dark. In areas away from adipose tissue, epithelium could be imaged to depths greater than 0.3 mm albeit with less resolution than when at the surface. Epithelial proliferations could be detected but not graded at that depth. With advances in the design of the tissue carrier that would allow for imaging on both sides of the carrier, we believe that it will be possible to image epithelium of smaller pieces of tissue to a combined depth of almost 1 mm.

Contrast in reflectance confocal imaging

Acetic and citric acid increases the endogenous backscatter from the nucleus to increase the contrast of the images. Increasing the contrast was straight forward with the needle core specimens; a 30 second immersion induced nuclear brightening throughout the imaging depth, although the nuclear brightness was greater near the surface than deep in the tissue. This difference can be attributed to reduced optical resolution deep in the tissue and reduced effect of the acid due to pH buffering of the tissue.

The cancerous regions often appeared brighter relative to the normal epithelium in the surrounding tissue, most likely due to the larger nuclei. However, the citric acid treatment did not provide specific contrast associated with cancer. Recent work with exogenous fluorescent dyes and 1 + -+ -NA -Normal and DCIS †While 10 cases were studied, sample 4 was excluded due to inadequate tissue handling. * Preparation Protocol: Preparation 1: Control; Preparation 2: Unbuffered 10% citric acid (1 min) and saline bath (5 min); Preparation 3: Buffered 10% citric acid (1 min) and glycerin (3 min) without saline; Preparation 4: Glycerin (3 min) without saline; Preparation 5: Buffered 10% citric acid (1 min) and glycerin (3 min) and saline bath; Preparation 6: Buffered 10% citric acid (1 min) without saline bath; Preparation 7: 5% Acetic acid (5 min) without saline bath; Preparation 8: Glycerin (3 min) with saline bath (5 min); Preparation 9: Unbuffered 10% citric acid (1 min) and glycerin (3 min) with saline bath (5 min); Preparation 10: 5% Acetic acid (1 min) and glycerin (3 min) without saline bath; Preparation 11: Mixture of buffered 10% citric acid and 5% acetic acid (1 min) and glycerin (3 min) without saline bath. nano particles that attach to dysplastic or cancerous tissue may provide enhanced cancer specific contrast [16][17][18]. These dyes and nano particles require more elaborate staining protocols, including additional steps to differentiate the contrast agent. Compatibility studies will need to be carried out to ensure that they do not affect the routine prognostic studies, such as immunohistochemistry and FISH, used in the clinical care of breast cancer patients. However, these agents demonstrate our ability to specifically label cancerous regions and may aid in the rapid detection of cancer in breast specimens in the future.

Confocal scanning laser microscopy has many potential applications in the practice of surgical pathology. Rapid diagnoses or determinations of adequacy could be given on core biopsy specimens, margins could be assessed by either ex vivo tissue imaging or intraoperative consultations at the time of primary surgical excision and CSLM could aid in the selection of sections to submit for microscopic study in large primary excisions or in the evaluation of re-excision specimens. These applications could result in a decreased time to diagnosis, reduced rate of reexcision, lower cost of pathology specimen processing, and improved patient care.

Although the size of this study is limited, the cases imaged represent a spectrum of breast conditions that require biopsy as determined by radiographic examination and patient history. We show that important morphological features of breast conditions can be imaged using CSLM. Our results call for further studies of percutaneously retrieved or open surgical specimens using reflectance or fluorescence confocal imaging with either single wavelength systems or newer multi-wavelength devices. In addition, we advocate the construction of a comprehensive atlas to develop the diagnostic criteria necessary for confocal screen of breast specimens.

Conclusion

Morphologic and cellular features of benign and cancerous lesions were identified in the confocal images. The images contained sufficient information to identify stromal reactions such as fibrosis, and cellular proliferations such as ductal carcinoma in situ and infiltrating carcinoma, and were comparable to standard histologicallyprepared sections of the same tissue. Confocal images can be enhanced by immersing the tissue in 5% citric acid solution for 30 seconds and then immersing and viewing it in glycerin. After confocal imaging, the tissue remains intact and available for standard histological processing, including the use of immunohistological stains. The effects of citric acid and glycerin immersion on subsequent histologic processing are demonstrated. Tissue treated with 5% acetic acid or 5%-10% citric acid should be bathed in saline for 5 minutes prior to fixation, and the pH of either acetic acid or citric acid should be buffered to pH>2.4 to preserve receptor reactivity.

Because reflectance confocal images are visually different from traditionally processed histological sections, an atlas of comparative pathology is needed. To further build an atlas, additional studies are required to develop a comprehensive understanding of the correlation of confocal images to traditionally prepared slides for the various conditions and diseases of the breast. data management for the study, selection of cases presented in the study, selection of confocal images presented in the study, drafting of the manuscript and final approval of the manuscript. All authors read and approved the final version of the manuscript.

. Representative confocal images (A) and corresponding H&E images (B) are shown in the figures [Figures, 1, 2, 3, 4, 5, 6 &7]. All scale bars are 50 μm in length.

Figure 1 Fibrocystic
1changes. CSLM (A) and H&E (B) images show the lumen of a cyst (*) lined by a layer of small, somewhat flattened epithelial cells (arrows). The nuclei of stromal cells (spindle shaped fibroblasts and rounded lymphocytes) are evident adjacent to the cyst (arrowheads).

Figure 2 Fibrocystic
2changes. CSLM (A) and H&E (B) images show the microanatomy of the branching terminal duct lobular unit and the epithelial lining of a microcyst. Fibroblasts in the surrounding stroma contain bright nuclei (arrowheads). Apocrine metaplasia Figure 3 Apocrine metaplasia. The intensity of the nuclei in the CSLM image (A) may be attributed to better permeation of the citric acid solution in this partially fragmented specimen. The fine granularity of the cytoplasm corresponds to the eosinophilic granularity of apocrine cells in the H&E (B).

Figure 4
4Ductal carcinoma in situ, nuclear grade 2. (A) Lumens of the ducts are filled with neoplastic cells with nuclear atypia (*). The nuclei in the CSLM images, represented by the irregular oval to circular granular white structures, are crowded and abnormally arranged. (B) The distinction between atypical hyperplasia and low grade ductal carcinoma in situ cannot always be made on the basis of the CSLM image.Infiltrating ductal carcinoma, nuclear grade 1 with tubular featuresFigure 5 Infiltrating ductal carcinoma, nuclear grade 1 with tubular features. (A) The well-defined nature of the infiltrating groups of cells and the relatively small, uniform nuclei (arrows) is evident in both images. Sequentially captured 16-image stacks demonstrated central lumens in some of the groups. The lumens of the tubular-like structures are better defined in the H&E image (B).

Figure 7
7Poorly differentiated infiltrating ductal carcinoma, nuclear grade 3. Although the margins of the nuclei are not sharply defined in CSLM (A), the arrangement of tumor cells in diffusely infiltrating nests and aggregates (*) is evident. Residual fat cells are seen as dark, round spaces (arrows). The H&E image (B) shows sharper definition of the nuclear features in this case.

Table 1 :
1Representative CasesRadiologic
Impression/
Technique

Patient
BI-RADS
Category

Needle Gauge
(G)

Pieces of tissue in
specimen

Pieces of tissue
imaged

Pathologic diagnosis

Calcium positive/
mammogram

1
4
11
7
1
Fibrocystic changes with
calcifications
mass/mammogram,
ultrasound

2
4
14
4
1
Fibrocystic changes with
calcifications
mass/sonogram
3
3
14
3
1
Fibrocystic changes with
apocrine metaplasia
Calcium positive/
mammogram

4
4
11
5
1
Ductal carcinoma in situ

Speculated mass/
Mammogram,
sonogram

5
4
14
3
1
Infiltrating ductal
carcinoma

Mass/mammogram,
ultrasound

6
5
14
2
1
Infiltrating lobular
carcinoma
Palpable mass/
ultrasound

7
5
14
5
1
Poorly differentiated
infiltrating ductal
carcinoma

Table 2 :
2Compatibility Study ResultsSample †
Preparation* Protocol
ER
PR
HER 2/nu
Pathologic diagnosis
Normal
Cancer
Normal
Cancer
Normal
Cancer

1A
1
NA
+
NA
+
NA
-
DCIS
1B
2
NA
+
NA
-
NA
-
DCIS
1C
3
NA
+
NA
+
NA
-
DCIS
2A
1
NA
-
NA
-
NA
+
DCIS
2B
4
NA
-
NA
-
NA
+
DCIS
2C
5
NA
-
NA
-
NA
+
DCIS
3A
1
+
NA
+
NA
NA
NA
Normal
3B
6
+
NA
+
NA
NA
NA
Normal
3C
5
+
NA
+
NA
NA
NA
Normal
5A
1
NA
-
NA
-
NA
+
DCIS
5B
5
NA
-
NA
-
NA
+
DCIS
5C
4
NA
-
NA
-
NA
+
DCIS
6A
1
+
-
+
-
NA
-
Invasive DC
6B
4
NA
-
NA
-
NA
-
Invasive DC
6C
5
NA
-
NA
-
NA
-
Invasive DC
6D
8
NA
-
NA
-
NA
-
Invasive DC
7A
1
+
NA
+
NA
NA
NA
Normal
7B
9
-
NA
+
NA
NA
NA
Normal
7C
10
-
NA
+
NA
NA
NA
Normal
7D
5
+
NA
+
NA
NA
NA
Normal
8A
5
+ weak
NA
+
NA
NA
NA
Normal (atrophic)
8B
1
+ weak
NA
+
NA
NA
NA
Normal (atrophic)
8C
1
+ weak
NA
+
NA
NA
NA
Normal (atrophic)
9A
5
NA
-
NA
-
NA
-
Invasive DC
9B
1
NA
-
NA
-
NA
-
Invasive DC
9C
1
NA
-
NA
-
NA
-
Invasive DC
10A
5
+
NA
+
NA
NA
NA
Normal
10B
3
+
NA
+
NA
NA
NA
Normal
10C
11
+
-
+
-
NA
-
Normal and DCIS
10D

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AcknowledgementsTi-Ba LLC, Rochester, NY provided the VivaScope 2000 reflectance confocal microscope used to image the specimens in the second compatibility study. The authors are grateful to Dr. Wende Logan-Young and the radiology technicians at the Elizabeth Wende Breast Clinic for their assistance with specimen selection and data acquisition, to Wanda Torres (Lucid, Inc.) and Sarah Hanson (EWBC) for their help with data acquisition and data processing, and to Cortney Jansen (Lucid, Inc.) for technical assistance. We would also like to thank Dr. Agnes Liman for her assistance in processing the second compatibility study specimens, and Ms. Laurie Baxter and Daniel Eversole (all of the University of Rochester) for technical assistance.Competing interestsLMS declares no financial or non-financial competing interests. JNB declares that he is a shareholder of Lucid, Inc. common stock. TABdeclares no financial or nonfinancial competing interests. JMZ declares that he was formerly the Vice Present of Technology at Lucid, Inc. At the time this study took place he was managing and currently manages Lucid's intellectual property portfolio on a part-time basis. He is also a shareholder of Lucid, Inc. common stock. MZ declares no financial or non-financial competing interests. CAF is an employee of Lucid, Inc. and a shareholder of common stock in the Company.Authors' contributionsLS contributed in the selection, analysis and interpretation of the confocal images and histology as well as drafting of and final approval of this manuscript. JNB contributed in the selection of the seven cases that were represented, the selection of the individual confocal images and histology that were chosen to represent the cases, the drafting of and final approval of the manuscript. TB contributed to the conception, design and execution of the first and second compatibility studies, histological analysis of the specimens in the first and second compatibility studies, the conception and design of the overall study, analysis and interpretation of the confocal images and histology, and the final approval of the manuscript. JZ contributed to the conception, design and execution of the first and second compatibility studies, the conception and design of the overall study, selection of cases that were represented in the study, selection of confocal images presented in the study, drafting of and final approval of the manuscript. MZ contributed in the conception and design of the overall study, selection of specimens core biopsy submitted to the study as well as drafting of the manuscript and final approval. CAF contributed in the design of the study, image acquisition andPre-publication historyThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/265/pre pub
In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison to histology. M Rajadhyaksha, S Gonzalez, J Zavislan, R R Anderson, R H Webb, J Invest Dermatol. 113Rajadhyaksha M, Gonzalez S, Zavislan J, Anderson RR, Webb RH: In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison to histology. J Invest Dermatol 1999, 113:293-303.

A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: Confocal reflectance microscopy. W M White, G J Tearney, B Z Pilch, R L Fabian, R R Anderson, R D Gaz, Surgery. 6White WM, Tearney GJ, Pilch BZ, Fabian RL, Anderson RR, Gaz RD: A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: Confocal reflectance microscopy. Surgery 2000, 6:1088-2001.

Confocal Examination of Nonmelanoma Cancers in Thick Skin Excisions to Potentially Guide Mohs Micrographic Surgery Without Frozen Histopathology. M Rajadhyaksha, G Menaker, T Flotte, P Dwyer, S Gonzalez, J Invest Dermatol. 117Rajadhyaksha M, Menaker G, Flotte T, Dwyer P, Gonzalez S: Confo- cal Examination of Nonmelanoma Cancers in Thick Skin Excisions to Potentially Guide Mohs Micrographic Surgery Without Frozen Histopathology. J Invest Dermatol 2001, 117:1137-1143.

Laser Microscopy Enhances Mohs Surgery for Skin Cancer. I Schneider, Medical Laser Report. 156Laser Focus WorldSchneider I: Laser Microscopy Enhances Mohs Surgery for Skin Cancer. Laser Focus World, Medical Laser Report 2001, 15(6):.

In Vivo real-time confocal reflectance microscopy: a noninvasive guide for Mohs micrographic surgery facilitated by aluminum chloride, an excellent contrast enhancer. Z Tannous, A Torres, S Gonzalez, Dermatol Surg. 298Tannous Z, Torres A, Gonzalez S: In Vivo real-time confocal reflectance microscopy: a noninvasive guide for Mohs micro- graphic surgery facilitated by aluminum chloride, an excel- lent contrast enhancer. Dermatol Surg 2003, 29(8):839-846.

Confocal microscopy of excised human skin using acetic acid and crossed polarization: rapid detection of non-melanoma skin cancers. R R Anderson, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X. Proceedings of SPIE. Anderson RR, (ed), et al.: Confocal microscopy of excised human skin using acetic acid and crossed polarization: rapid detection of non-melanoma skin cancers. Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems X. Proceedings of SPIE; 22-23, 25 Jan 2000;

. San Jose, 3907USASan Jose, USA 3907:.

Evaluation of Hepatic Histology by Near-Infrared Confocal Microscopy: A Pilot Study. V Campo-Ruiz, E R Ochoa, G Y Lauwers, S Gonzalez, Human Pathology. 3310Campo-Ruiz V, Ochoa ER, Lauwers GY, Gonzalez S: Evaluation of Hepatic Histology by Near-Infrared Confocal Microscopy: A Pilot Study. Human Pathology 2002, 33(10):975-982.

Evaluation of Morphology and Microcirculation of the Pancreas by Ex Vivo and In Vivo Reflectance Confocal Microscopy. T Keck, V Campo-Ruiz, A L Warshaw, R R Anderson, C Fernandez-Del Castillo, S Gonzalez, Pancreatology. 1Keck T, Campo-Ruiz V, Warshaw AL, Anderson RR, Fernandez-del Castillo C, Gonzalez S: Evaluation of Morphology and Microcir- culation of the Pancreas by Ex Vivo and In Vivo Reflectance Confocal Microscopy. Pancreatology 2001, 1:48-57.

Reflectance Confocal Microscopy for Characterization of Mammary Ductal Structures and Development of Neoplasia in Genetically Engineered Mouse Models of Breast Cancer. A Parrish, E Halama, M Tilli, M Freedman, Furth , J Biomed Op. 10551602Parrish A, Halama E, Tilli M, Freedman M, Furth : Reflectance Con- focal Microscopy for Characterization of Mammary Ductal Structures and Development of Neoplasia in Genetically Engineered Mouse Models of Breast Cancer. J Biomed Op 2005, 10(5):051602.

Real-time imaging and characterization of human breast tissue by reflectance confocal microscopy. M T Tilli, M C Cabrera, A R Parrish, K M Torre, M K Sidaway, A L Gallagher, E Mikariou, S A Polin, M C Liu, P A Furth, J Biomed Op. 12551901Tilli MT, Cabrera MC, Parrish AR, Torre KM, Sidaway MK, Gallagher AL, Mikariou E, Polin SA, Liu MC, Furth PA: Real-time imaging and characterization of human breast tissue by reflectance con- focal microscopy. J Biomed Op 2007, 12(5):051901.

Comparison of mouse mammary gland imaging techniques and applications: reflectance confocal microscopy, GFP imaging, and ultrasound. M T Tilli, A R Parrish, I Cotarla, L P Jones, M D Johnson, P A Furth, BMC Cancer. 821Tilli MT, Parrish AR, Cotarla I, Jones LP, Johnson MD, Furth PA: Comparison of mouse mammary gland imaging techniques and applications: reflectance confocal microscopy, GFP imaging, and ultrasound. BMC Cancer 2008, 8:21.

Changing Paradigms in Dermatology: Confocal Microscopy in Clinical and Surgical Dermatology. S Gonzalez, K Swindells, M Rajadhyaksha, A Torres, Clinics in Dermatology. 210Gonzalez S, Swindells K, Rajadhyaksha M, Torres A: Changing Par- adigms in Dermatology: Confocal Microscopy in Clinical and Surgical Dermatology. Clinics in Dermatology 2003, 21:000.

Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents and limits of contrast. C Smithpeter, A K Dunn, R Drezek, R Richards-Kortum, J Biomed Opt. 3Smithpeter C, Dunn AK, Drezek R, Richards-Kortum R: Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents and limits of contrast. J Biomed Opt 1998, 3:429-436.

Confocal Examination of Non-Melanocytic Cancers in Thick Skin Excisions to potentially Guide Mohs Micrographic Surgery without Frozen Histopathology. M Rajadhyaksha, G Menaker, T J Flotte, P Dwyer, S Gonzalez, J Invest Dermatol. 1175Rajadhyaksha M, Menaker G, Flotte TJ, Dwyer P, Gonzalez S: Confo- cal Examination of Non-Melanocytic Cancers in Thick Skin Excisions to potentially Guide Mohs Micrographic Surgery without Frozen Histopathology. J Invest Dermatol 2001, 117(5):1137-43.

Determination of the refractive index of highly scattering human tissue by optical coherence tomography. G J Tearney, M E Brezinski, J F Southern, B E Bouma, M R Hee, J G Fujimoto, Opt Lett. 20Tearney GJ, Brezinski ME, Southern JF, Bouma BE, Hee MR, Fujimoto JG: Determination of the refractive index of highly scattering human tissue by optical coherence tomography. Opt Lett 1995, 20:2258-2261.

Confocal mosaicing microscopy in Mohs skin excisions: feasibility of rapid surgical pathology. D Gareau, Y Li, B Huang, A Eastman, K Nehal, M Rajadhyaksha, J Biomed Opt. 13554001Gareau D, Li Y, Huang B, Eastman A, Nehal K, Rajadhyaksha M: Con- focal mosaicing microscopy in Mohs skin excisions: feasibility of rapid surgical pathology. J Biomed Opt 2008, 13(5):054001.

Gold based nanoparticles for breast cancer diagnosis and treatment. J Xing, J Zeng, J Yang, K Tao, T Xu, W Roa, X Wang, J Chen, Proceedings of 2007 IEEE International Symposium of Circuits and Systems. 2007 IEEE International Symposium of Circuits and SystemsNew Orleans, USAXing J, Zeng J, Yang J, Tao K, Xu T, Roa W, Wang X, Chen J: Gold based nanoparticles for breast cancer diagnosis and treat- ment. Proceedings of 2007 IEEE International Symposium of Circuits and Systems, New Orleans, USA. May 27-30, 2007 .

Molecular specific optoacoustic imaging with plasmonic nanoparticles. S Mallidi, T Larson, J Aaron, K Sokolov, S Emelianov, Opt Express. Mallidi S, Larson T, Aaron J, Sokolov K, Emelianov S: Molecular spe- cific optoacoustic imaging with plasmonic nanoparticles. Opt Express 2007:6583-6588.


Ethical challenges in surgery as narrated by practicing surgeons

Kirsti Torjuul email@example.com
Faculty of Nursing
Sør-Trøndelag University College
Trondheim, Norway

Ann Nordam
Centre for Medical Ethics
University of Oslo
Norway

Venke Sørlie
Institute of Nursing and Health Sciences
Faculty of Medicine
University of Oslo
Norway

BMC Medical Ethics

Ethical challenges in surgery as narrated by practicing surgeons
10.1186/1472-6939-6-2BioMed Central Page 1 of 10 (page number not for citation purposes) Research article
Background:The aim of this study was to explore the ethical challenges in surgery from the surgeons' point of view and their experience of being in ethically difficult situations.Methods: Five male and five female surgeons at a university hospital in Norway were interviewed as part of a comprehensive investigation into the narratives of nurses and physicians about being in such situations. The transcribed interview texts were subjected to a phenomenologicalhermeneutic interpretation.Results:No differences in ethical reasoning between male and female surgeons were found. They reasoned in both action and relational ethical perspectives. Surgeons focused on their relationships with patients and colleagues and their moral self in descriptions of the ethical challenges in their work. Dialogue and personal involvement were important in their relationships with patients. The surgeons emphasized the importance of open dialogue, professional recognition, and an inclusive and accepting environment between colleagues.Conclusion:The surgeons are personally challenged by the existential realities of human life in their relationships with patients. They realized that ethical challenges are an inherent part of performing surgery and of life itself, and say that they have to learn to "live with" these challenges in a way that is confirmed both socially and by their inner moral self. This means accepting their personal and professional limitations, being uncertain, being fallible, and being humble. Living with the ethical challenges of surgery seems to contribute to the surgeons' confidence and vulnerability in their professional identity.

Background

It is important for surgeons to be and to act in a right and good way towards patients, relatives, and colleagues. Studies have shown, however, that physicians often are in doubt about the best and correct actions to take for the patients in specific situations [1][2][3]. This question is not only a medical one, but can be understood in both action ethics and relational ethics perspectives. An action ethics perspective concerns questions as to what ought to be done in ethically difficult situations and why. In this perspective, ethics often centres on difficult ethical dilemmas and decision-making. Ethical dilemmas occur when physicians have to choose between at least two alternative and equally difficult courses of actions. Because neither of the alternatives have positive outcomes, they have to choose between two evils [4]. Ethical dilemmas can also be understood as conflicts between different courses of action that result from general and mutually exclusive ethical principles in medicine [5].

A relational ethical perspective means reflecting on the challenges we encounter in our relationships with others and how to fulfil our social roles and obligations in a good way -as a human being, a surgeon, and a colleague.

It tries to answer questions such as "How can I adequately meet the challenges that confront me in the relationships in which I am involved in this situation?" [4]. The qualities that make a person a good physician are not only individual traits but they are characteristics of the relationships. One way to describe a good physician or a surgeon is to count the number of characteristics or virtues which are portrayed. According to MacIntyre [6], another way is to speak about a good physician or a surgeon. Narrative ethics focus on what life demands from us in different situations and how we ought to respond to these challenges [4,6,7].

Action and relational ethical perspectives are not interchangeable as surgeons have a dual responsibility for their actions in specific situations as well as their way of being in their relationships [4,7]. Being a good surgeon presupposes both professional competencies based on scientific and clinical knowledge and skills, and being present and showing respect and compassion for patients [4,5,8]. Physicians become involved in the patients' problems both in a professional and moral sense [9]. Traditionally, it has been assumed that compassion can impair competence and that they cannot coexist [10].

Many authors argue that the respect and trust in the physician-patient relationship have eroded in recent years in spite of the physicians' increased therapeutic capabilities [11,12]. Shorter hospital stays and organizational changes in the hospitals are said to lead to surgeons spending more time in the operating theatre and less time talking to patients and establishing a trusting relationship [7,13]. An open and honest dialogue between physicians and patients can be difficult to achieve as medicine becomes more complex, fragmented, episodic, and impersonal, according to Jones [14].

Medical problems are always existential problems too because suffering, anxiety, life, death, and cure involve the core of human existence. Physicians are working with emotionally intense issues and have to accept the possibility of failures, continuing suffering, and death on the part of their patients [12]. Meeting patients who are emotionally distressed or tragically injured can make surgery emotionally challenging [15]. Patients may also elicit emotions of anger and frustration, fear, and despair in physicians [16]. Research suggests that the delivery of bad news can be particularly troubling for both patients and physicians because of the emotional component, and that physicians experience great discomfort in such situations [17]. Physicians have to function at an optimal level despite these challenges. Straume [18] regards the physicians' vulnerability as a result of their overwhelming responsibility and experience that patients' demands often exceed the physicians' ability.

Although most clinicians are aware of the uncertainty and the limitations of medicine and their responsibility to try to reduce the likelihood of error, [19,20] the boundary between medical errors and accidents is not evident [21][22][23]. Physicians may have difficulty acknowledging personal errors because they can be experienced as personal defeats and thus confirm that physicians are vulnerable [20,24].

Surgeons' relationships with their colleagues have become more important as surgery has changed from relying heavily on the performance of individual surgeons to relying on a team of providers [8,25]. Several studies have found a lack of dialogue and support structures among physicians [26,27]. Physicians are said to have no tradition for open discussions about uncertainty and conflict areas in their practice, nor are they comfortable talking openly about their personal emotions and problems [12,16,24]. Adverse events are said to be generally managed by the conspiracy of silence [20,22].

The vulnerability of patients is emphasized in the literature of medical ethics. Less is written about the vulnerability of the physicians in their relationships with patients, relatives, and colleagues. Being involved may engender feelings of helplessness and vulnerability in the physician. MacLeod [28] argues that physicians have to accept their vulnerability and be able to express and share it in order to be able to live with the tensions. Little [29] suggests that understanding the peculiarities and intensity of the patient-surgeon relationship may help the surgeons understand the vulnerability of both patients and surgeons.

Studies show that physicians seem to experience uncertainty and fallibility in different ways. Less experienced female physicians in paediatric care put on an air of certainty while the more experienced gained a kind of security by allowing themselves to feel uncertain [30]. Female physicians in geriatric care seemed to accept their own vulnerability and fallibility [31]. Experienced male physicians in pediatric care related personal security to their professional experience while the less experienced thought that advances in medical knowledge and ethical guidelines would make them more secure in their work [32]. Henriksen and Hansen [33] found that general practitioners seemed to strive for the ideal of a humble attitude towards problems; being too self-confident was regarded as a threat because of the increased risk of downfall.

Few empirical studies have been found that explore the ethical challenges of surgery from the surgeons' point of view and their experience of being in ethically difficult situations. The present study is part of a comprehensive investigation of ethical reasoning among male and female physicians and nurses within surgical units. The results of this interview study with male and female surgeons will be presented in two articles. The present study describes the surgeons' experiences of being in ethically difficult situations from a relational ethics perspective. The other paper describes the ethical dilemmas as experienced by the surgeons from an action ethical perspective. The results from the interviews with the registered nurses (RNs) working in surgical units are in progress and will be addressed in a third paper.

The aim of this study is to explore the meaning of being in ethically difficult situations in surgery as narrated by male and female surgeons.

Methods

Participants and setting

Five male and five female surgeons working on surgical units at a university hospital in Norway participated in the study. All were experienced and had been working in health care from 9 to 31 years (median = 21.5), and in surgery between 5 to 21 years (median = 13). The surgeons worked full time and were on duty when the interviews were conducted. No individual characteristics will be disclosed in order to guarantee confidentiality. The surgeons gave their informed consent to participate in the study, which was also approved by the 5 th Regional Ethics Committee in Norway.

Data collection Interviews

The interviews were conducted by the first author and lasted from 35 to 75 minutes (median = 55). They were tape recorded and subsequently transcribed verbatim. The interviewees were asked to tell about one or more ethically difficult care situations that they had experienced in their work as surgeons. What constituted an ethically difficult situation was not defined, allowing the interviewees to determine what they considered ethically difficult themselves. The aim of the interviews was to obtain as many rich narratives as possible without interrupting the surgeons' narrative flow and reflection. If the surgeons did not spontaneously reflect on the events they talked about, their reflections were sought. Questions were asked when the interviewer wanted the interviewees to elaborate on their stories or had difficulty understanding the narration.

These questions referred to the interviewees' thoughts, feelings, and actions [34]. Field notes were taken during the interview as aids to the interviewer's memory and in order to make it possible to understand the interview text in relation to its context, e.g. arrangements and interruptions. Nonverbal communications that seemed relevant were also noted, such as laughter and long pauses. The transcribed text was compared with the field notes and adjusted if necessary.

Data analysis Interpretations

The method of interpretation used was inspired by the French philosopher Paul Ricoeur's phenomenological hermeneutics [35], and developed at the University of Tromsø (Norway) and Umeå University (Sweden) and has previously been used by Lindseth et al., [36] Udén et al., [1,13] Søderberg et al., [37] and Sørlie et al. [30,32,38]. This method is useful to elucidate the narratives of people's experiences. The method of interpretation proceeds through three phases, which constitute a dialectical movement between the whole and the parts of the text and between understanding and explanation [35].

Each interview was regarded as a text. However, it was not what the texts said that was a subject matter to be investigated, but rather the focus was on the ethics expressed in them or the essential meaning of ethically good phenomena (or the essential meaning missing in ethically poor phenomena) [39]. First, a naïve reading was made of all the transcribed interviews as a whole to gain a first impression of the surgeons' experiences of being in ethically difficult situations during their clinical work. The repeated naïve reading was made as open-minded as possible, without any deliberate analysis of the text. The naïve reading shows the direction the structural analysis may take. Second, a structural analysis was performed in order to validate or refute the initial understanding obtained from the naïve reading and to explain what the text was saying. The interviews were divided into meaningful parts and patterns, i.e. one sentence, parts of a sentence, or a whole paragraph with a related meaning content. The meaning units were condensed and discussed among all the authors, and themes and subthemes were identified, and presented in 'Results'. Third, a comprehensive understanding was developed, taking into account the authors' preunderstanding, the naïve reading, and the structural analysis (results). The text was read as a whole and interpreted in relation to relevant theories of ethics and results from previous investigations into the meaning of being in ethically difficult care situations [39]. The comprehensive understanding is presented under the heading 'Discussion'. The analysis was conducted by all the authors and the interpretative agreement was considered satisfactory and to be the most useful understanding of the meaning of the surgeons' experiences of situations of ethical difficulty. The authors' interpretation was not shared or validated with the surgeons. In this study, the focus was on obtaining the meaning of the text, which cannot be validated by the interviewees. A kind of validation is accomplished by the structural analysis as the objective part of the interpretation process [39]. According to Ricoeur [35] a text has multiple but not infinite meanings. One particular phenomenological hermeneutic interpretation should therefore be seen as one of several possible interpretations and as arguments put into ongoing discourses, in this case, about ethical challenges in surgical care.

Results

Several readings of the interview texts revealed that the surgeons told about ethical challenges that confront them in their relationships with patients and colleagues and about their experiences of living with these challenges. They also reported their experiences of ethical dilemmas in surgical practice. No gender differences between the male and female surgeons were found in the analysis of the interviews. The results showed that each surgeon created many and detailed narratives. When the surgeons were asked to narrate their experiences, they did not differentiate between action and relational perspectives in their ethical reasoning. This is an analytical distinction made by the authors in order to structure the results. The authors therefore decided to separate the presentation of the results in two papers: one paper about the surgeons' experiences of being in ethically difficult situations from a relational ethics perspective and the other paper from an action ethical perspective according to the theory presented in the introduction [4]. This paper presents the ethical challenges of surgery as narrated by five male and five female surgeons.

The themes and the subthemes from the structural analysis are shown in Table 1 and presented in the text below. Direct quotations from the interviewers are included to illuminate the results.

Dialogue with patients Openness and honesty

The surgeons emphasized the importance of dialogue with patients and especially being open and honest about all aspects of their treatment and care. Talking to patients about difficult issues before or after the operation is experienced as an important part of the surgeons' responsibility. Openness and honesty is especially important when surgeons had to tell patients that they have cancer or a fatal disease, when something had gone wrong, or the operation did not turn out as successful as expected. Using frightening words such as "death" and "cancer" is also considered to be part of an open and honest dialogue. The surgeons also felt responsible for "not involving patients with bad news they were not ready to receive, and feeling one's way in what it's right to inform about". They said that if the patients are taken seriously and are talked to in a way that they understand, there is seldom difficulty reaching a mutual understanding about diagnostics and treatment.

The patients are always told the truth about their disease, although it was experienced as an emotional burden for the surgeons to disclose bad news or present difficult decisions to the patients. "It's a burden to tell the patient that we will withdraw all active treatment. You feel a bit guilty; in a way you feel that it's your fault if the treatment does not succeed". They stressed that knowing the patient from previous meetings is important to them, as is having antennae for how the patients experience their life and the present situation. "If I do not manage to achieve what I am trying to do, I always tell [the patients] what the situation is. I never try to conceal anything. That will only torment them".

Talking openly with patients is also important for the surgeons in situations when they are in doubt about the right thing to do. They experienced relief if the patient had an answer to their doubts. They said that patients who are seriously ill usually have thought about life and death issues and have a conception of their condition, and that the question of withholding or withdrawing treatment seldom comes as a surprise to them. Some patients say that they have lived a good life and do not want an operation. Others strongly want an operation even though their prognoses are poor. "We often reach an agreement about ending a treatment that either does not lead to a The surgeons are involved in many patients' lives and destinies and said that keeping a certain distance protects their feelings and is a way of caring for themselves. They said that keeping a certain distance is necessary in order to give the patient neutral advice and the most suitable medical treatment. The surgeons feel a responsibility to care in situations where they find it difficult, for instance when they dislike the patients' personality, behaviour, or values. They said they work hard to get involved and care for demanding and non-compliant patients.

Social confirmation

Professional recognition Ethical challenges are discussed in both formal and informal social arenas among the surgeons. All new patients are presented at the daily morning meeting between all the surgeons, including what had been done to them and why. Only questions and short objections to the patients' diagnostics and treatments are raised at these meetings or shortly after. The surgeons arrange separate meetings to discuss problematic cases. "We assemble the nurses, the anaesthesiologists, the surgeons, and even other specialists like the nephrologists when we have patients who reside a long time in the intensive care unit. In a way we create a meeting-place for the case and discuss whether we should withdraw a life-sustaining treatment or start additional treatment for a kidney failure for instance." The informal running dialogues during the day were equally important for the surgeons. "You have to make the decision yourself, but we always discuss the problem together before difficult decisions are made. The discussions do help and are experienced as mutual support". The surgeons expressed confidence in the consensus that usually is achieved in these discussions. "I know that I would be content to receive the treatment we agree upon myself".

The surgeons emphasized the importance of having a caring relationship with their colleagues. They said that talk-ing together and giving and receiving collegial support is necessary in order to live with the personal responsibility of being in ethically difficult situations and with the emotional burden of decision making. "People say that surgeons are a bit tough and do not talk about feelings, and that may be true. But in my experience we really care for each other. Perhaps we do not go all mushy about our feelings, but we understand when someone is in difficulty. I have experienced receiving good support in such situations. Colleagues contact you and say: "Ok, listen, a couple of years back the same thing happened to me", or: "You must not take this too hard, it could have happened to anybody". That helps".

Personal and emotional support is informally and silently shared among trusted colleagues and great value is attached to it. After having presented a difficult decision about withholding treatment at a morning meeting, one of the surgeons commented: "That same afternoon, four or five of the most experienced surgeons came to me independently, and told me that they thought that what I had done was great. They said that most surgeons were not able to do what I had done. I remember it well because I think it was so well said".

Open dialogue

The surgeons emphasized the importance of "playing with an open hand" and that openness and honesty in the relationships with colleagues presupposes a trusting atmosphere that allows everybody to feel free to voice their opinion and be listened to. They feel that it is important that everyone who is involved in the treatment and care of the patient should have an opportunity to express their opinion and to be heard before any final decision is made. Openness and honesty are particularly important when medical errors occur or when something has gone wrong during an operation. Talking about medical errors or mistakes is considered an opportunity for learning and for improving surgical routines. "You have to have an including and accepting environment that allows you to say that you could have chosen a different solution. If there is no room for you saying something like that, then there will be a tendency to conceal it. We all make mistakes and we all make wrong deliberations and sometimes choose bad solutions. We have to live with that. Therefore it's important that we try to learn from the cases where something [erratic] happens".

The surgeons focused on the necessity of dialogue and cooperation with their colleagues. "We are used to working close together in a team and it makes these difficult situations easier to handle". They found it satisfactory to work in a hospital because "there is always someone you can ask for advice when in doubt". They said they find it easier to talk to patients about difficult treatment options when the question has been discussed with experienced colleagues or senior surgeons first. This is especially important for less experienced physicians. The surgeons also make a contrast between the importance of cooperation with colleagues and the burden of being alone and being responsible decision makers.

Self-confirmation Responsibility

The surgeons said that they experience ethically difficult situations as an important part of their everyday activities that cannot be separated from the rest. "These situations are a part of our profession that are not necessarily experienced as difficult, but are sometimes unpleasant to be in". They said they have to experience these situations personally and be involved in order to understand them and to learn to live with them.

Some ethically difficult situations are experienced as dramatic and tragic, especially when the surgeons feel the personal responsibility for saving the lives of trauma patients after major accidents. "If you are not able to cope with being in this situation and be responsible, and be the leader of the trauma team trying to save peoples' lives after a serious accident, if you cannot do that but go on wondering if you have done something wrong, then I think you will find something else to do".

The surgeons told about situations where they are alone on duty and responsible for rapid deliberations and decisions in acute and emergency situations as especially challenging. "There are no other times in this job when you feel as lonely as you do in those situations". The decision whether to continue or withdraw treatment from traumatized young patients and children is experienced as especially challenging to make alone. "It's not easy [being alone]. It's the kind of decisions you often ponder about for several days afterwards, also at home. It's the sort of decisions you really try to closely think through, and it often troubles you even after you have made a decision".

The surgeons said they have to learn to live with the unpredictable consequences of their decisions. "The practice of surgery is very specific and you feel more responsible in a way than in other areas of medicine. You have the feeling of being the direct cause when things go wrong, e.g. that you operated at the wrong time, you operated incorrectly or that you should have found the right diagnosis earlier".

Uncertainty

The surgeons spoke about "living with" the inherent uncertainty of surgery and emphasized that they can never be completely sure of the right thing to do in ethically difficult situations. They have to live and work with the uncertainty of the course of the disease, the patients' chances of survival, the risk of serious and fatal complications and the uncertainty of the patients' quality of life after extensive operations. The surgeons said they have to learn to live with the uncertainty of their deliberations and operations as there can be no right answer to ethical challenges, and no criteria to guide them when they make their decisions.

Living with uncertainty is experienced as both frightening and satisfying. The surgeons said that not knowing what to do in an uncertain situation, finding a way, and succeeding in their attempt to restore health or save life is a satisfying aspect of their work. They also commented that they have to live with their doubts and fears of being too active and the risk of knowingly imposing severe complications and a poor quality of life on their patients.

Fallibility

The surgeons said that their aim is to make all patients better. Accepting the limitation of surgery and not being able to cure a particular patient or alleviate his or her suffering is not an easy task for surgeons. They commented that it feels difficult not to be able to or not to be allowed to help patients. Sometimes they feel guilty if the treatment does not succeed, but said that they have to accept the possibility of making mistakes as an essential part of the profession. "You have to face the reality of how things are. What we are dealing with are human beings in marginal situations where things can go wrong. Everybody who is dealing with these things makes errors of deliberation and judgment. It's a part of the game that you have to live with when the margins are so tight. It would not be better if you quit. Your dearly purchased experience will be of use to nobody then".

Confidence

The surgeons said that they are focused on healing and curing and that they try to operate on the patients in most situations. "I believe that surgeons feel that it's good to do something, curing, and saving lives. That is what we have learned to do. We are in a profession that can do many useful things and that is the gratifying part of practicing surgery, -that you can identify a problem and do something about it".

The clinical experience of deliberating and choosing and finding workable solutions in clinical and ethical difficult situations makes the surgeons confident. "Most surgeons are action-oriented. If not, it's almost impossible to practice surgery, because you have to makes decisions all the time and be accountable for your decisions". Receiving social confirmation from patients, relatives, and colleagues when they succeed contributed to the surgeons' experience of confidence in their own decisions and actions. The surgeons also said that having the courage of your convictions and a set of personal ethical values is equally important in order to do a "proper and conscientious job". This means acting according to the patients' best interests and the standards of their profession. Their conscience helps them to decide which action is morally wrong, to make controversial decisions, and to voice personal, professional, and moral opinions to colleagues and patients.

Humility

The surgeons emphasized that although they deal with existential issues of life and death, they do not rule over these human conditions. "The essence is that we are not almighty. We do not save lives, we just postpone death. The only thing that is certain is that we are all going to die. You are just doing repairs and trying to help the patients to live a bit longer. " "Fortunately it's not we who rule over life and death. What we can do means less than you think and that is how it should be. I think it's important that we all acknowledge this and everyone else too".

All the surgeons said they are against active euthanasia. They also commented that a humble attitude in their work helps them acknowledge their personal and professional limitations and to recognize what they cannot and ought not do. "There is a dimension in surgery of being right about having a good reason to operate and being considerate about the benefits of carrying out an operation".

Discussion

The surgeons in this study reasoned in a relational ethics perspective, focusing on dialogue, openness, and involvement in their relationships with patients and colleagues. While the surgeons in the interviews described their experience of being in ethically difficult situations, it seems at the same time that identity was central to their experience of ethics and their enactment of moral agency. The surgeons identified themselves by telling about their ethical experience, expressing the way they are living their identity. By narrating our lived experience, we give meaning to our experiences. We understand ourselves through the stories we tell and live, as well as those told about us and by interpreting them. Personal identity is said to be constructed through the stories we tell about our lives, stories which are in turn shaped by more general institutional, cultural, or national meta-narratives that live within the culture, of surgery, medicine, and society [40][41][42]. Thus, it seems that the surgeons' identity has a narrative structure and is narratively derived.

Being open and honest about all aspects of patients' treatment and care is experienced as important for the surgeons. This is even true in situations when they have to disclose bad news and tell the patient that they are not able to or did not succeed in their efforts to restore health. Openness of speech is one of the spontaneous expressions of life, designated as "utterances of life" according to the writings of Løgstrup [43]. That openness and honesty are spontaneous expressions means that they are performed in an unconstrained manner and without ulterior motives.

Human life means expressing oneself with the expectation of being met by others according to Løgstrup [43]. Openness and honesty are required in trusting relationships. When openness and honesty of speech are missing, closeness and dishonesty in the relationships result [43]. Sincerity in our relationships with others is a source of satisfaction and means being open and involved and allowing oneself to be moved and impressed by others according to Pahuus [44]. It is also probable that the surgeons' social confirmation increases when the patients meet surgeons who through dialogue turn out to be caring human beings.

Although disclosing bad news to the patient is experienced as an emotional challenge by the surgeons, concealing the truth does not seem to be an option they consider. Concealing the truth from the patient is experienced as difficult. It seems that surgeons need to share their experiences by speaking openly to patients so they can live with their demanding professional life in a satisfactory way. Therefore, honesty and openness are important because the relationships with patients are important for the surgeons' lives.

The surgeons said that it is important not to hide their uncertainty and doubts from themselves or from their patients. They accepted that uncertainty is an inherent part of their profession and realized that they often have to decide in spite of lack of scientific knowledge. They also deal with problems that may have no desirable solutions. Previous studies of surgeons [21], female physicians working in pediatrics, [30] and geriatrics [31] revealed that they are aware of and accept their own uncertainty and fallibility as inevitable in their professional lives.

The surgeons said that they sometimes feel guilty when they have to disclose the bad news to patients that the treatment did not succeed. We feel guilty when we fail to do what is required of us in a situation according to Løgstrup [43], either by not answering the ethical demand of the other or by betraying something valuable in our own life -values and beliefs we hold to be good and right. The surgeons are often in situations in which they have to use their clinical competence and practical wisdom to choose between conflicting values and obligations and being responsible for their decisions and actions. They can never know for certain in a given situation if their actions are absolutely right or wrong. They have to take risks, knowing that they may not succeed in their efforts to give patients a chance of survival.

Feeling guilty is our fundamental ethical condition as human beings according to Pahuus [44] because we have only limited possibilities at hand in particular situations and in life as a whole. Choosing one solution in a situation means excluding a multiple of other desirable possibilities. Thus, feeling guilty is a side effect of trying to give meaning and direction to our lives. Reflecting on our feelings of guilt means having a dialogue with and negotiating with our inner self, thereby evaluating what we hold to be important in our life with and for others. Feeling and being guilty is a heavy burden because human existence also contains that which is final, irreparable and cannot be changed [44]. Feeling guilty can also be understood in relation to what Ricoeur [40] has called an ethics of memory -that people never will or can and must not forget the bad or good things in history. The surgeons cannot and must not forget situations in which they failed to do the right or good thing.

The surgeons said that they experience a relief when the patients give answers to their own uncertainty and doubts about the right or good thing to do. It seems as if the surgeons are relieved when patients want to decide for themselves and take responsibility for their lives, appreciating that they do not hand over this responsibility to the surgeons. The surgeons in this study do not fit into the traditional and stereotypical picture of the paternalistic and authoritarian physicians [45]. On the contrary, the surgeons in this study seem to value being in a dialogue with patients and acknowledging their autonomy. Having to take responsibility for patients' lives is experienced as an ethical challenge and a personal burden in situations when the patients are unable to express their autonomy.

The surgeons emphasized the importance of being personally involved with the patients by focusing on patients as persons and their quality of life as much as their medical treatment. However, they experienced the challenge of finding the balance between involvement and distance in the relationships, between caring for the patients and themselves, and in giving professional and neutral information. Distance based on knowledge, skills, and experience with previous cases and situations is necessary in order to help the patients in a professional manner [43,46]. Personal involvement in a situation is necessary in order to know which fundamental values are threatened in both the patients' and the surgeons' lives. The aim of a dialogue is to abolish the distance between patients and surgeons in order to establish a space for mutual understanding. Involvement does not only mean acting according to the patients' expectations because surgeons are also responsible for their professional conduct as well as their moral integrity. Professional distance means taking the other's perspective in the situation, reflecting, deliberating, and using one's experience of similar cases. The surgeons also learned from their experiences through discussions and dialogue with experienced and trusted colleagues. They may throw new light on situations and increase the surgeons' abilities to deliberate and decide in their patients' best interests [46]. Finding the 'right' balance between involvement and distance in a situation is an expression of what Aristotle [47] calls practical wisdom (phronesis) or the practical knowledge of virtuous persons. A virtuous person is able to find the middle path between two extremes. The right and good thing to do in a particular situation involves "to the right person, to the right extent, at the right time, with the right motive, and in the right way" according to Aristotle [47].

In their narratives, the surgeons focused on cooperation and the relationships with their colleagues. They experienced being listened to and together they seem to create and recreate a collegial environment where they can express their doubts and admit their errors of deliberation and decisions.

The surgeons said that they experience taking difficult decisions alone as a burden. Working in a hospital is experienced as satisfying because they appreciate working together. They seemed to accept that they are mutually dependent on each other and appreciated the support they receive in dialogue with colleagues. Interdependence and exchange is a fundamental way of human lives according to the ethics of Løgstrup [43]. He calls this "display of life" which means that human beings are fundamentally dependent on one another and that we always are giving and receiving something in our relationships with others. This also means that each individual is challenged to take care of that part of the other's life that is in one's own power.

To be seen and listened to by colleagues, be taken seriously, and comforted when something goes wrong is an answer to fundamental human needs. Openness about personal doubts and failures also make the surgeons vulnerable. The interdependency among surgeons in this study is not experienced as a burden, but as mutual support. The surgeons' acceptance and appreciation of their collegial dependency may be an answer to why surgeons are able to stand in ethical difficult situations and live with them in a satisfying way. The dialogue with colleagues reduces the surgeons' doubts, although their doubts cannot and do not disappear.

The surgeons receive social confirmation for being good surgeons through dialogues with patients, relatives, and colleagues. Their experience of being of use to society as a whole also confirms their identity as good surgeons. To be confirmed is to be seen, listened to, and accepted by other persons. A person's identity is dependent on other persons in good or bad relationships according to Ricoeur [40], as well as an inner voice from the person's own consciousness.

The surgeons in this study emphasized the importance of dialogue with patients and colleagues. All identities are socially bestowed, socially sustained, and socially transformed and people make meanings of their actions by participating in communicative contexts. We all need recognition and social confirmation from others in order to construct our identities [41,48]. Thus the self-image of a surgeon can be maintained only in social contexts in which others are willing to recognize him or her in this identity.

There is a close relationship between identity management and values in a society since human beings usually want to be something they find valuable. What constitutes morality is created, recreated and communicated in social relations [41,49]. Narratives are a display of moral identity according to Jordens and Little [42], where the speakers present themselves as experienced, knowledgeable, and ethical. Institutional settings provide the narrative auspices under which identities are articulated. Telling stories is necessary for moral agency as we must be able to account for our actions and the actions of relevant others. We also tell stories as a sort of self-examination by selfexposure. We often find out what we think and who we are by listening to what we say.

The modern self is described as multi-voiced and dialogical and moral action is determined through a process of inner dialogue. To open up to the different voices within and enter into a dialogue, one can either reach consensus with oneself or experience conflict and dissatisfaction with oneself [41,49]. The surgeons' identities are constructed through negotiation with themselves, their patients, and colleagues within a context of social organization. The view of ourselves is shaped by the values of the larger society and what collectively is tacitly deemed to be right and good actions. Conversely, one's conception of how ethical the collective group is arises through one's personal view of what constitutes right and good actions [21,49]. Surgeons attempt to reconcile their relational experiences and their actions with their identity as moral agents as they live and practice relationally with others within the institutional values of their workplace.

The modernization and secularization of western societies emphasize the ideology of individual autonomy and freedom of choice. At the same time, the way in which social structures control and restrict individual performance and freedom becomes less visible. It is not in every person's or profession's power to choose, in other words, act as his/ her conscience directs [41]. The surgeons in this study seem to have a wide range of freedom to act in a way that is confirmed both from their patients, colleagues, society and by their inner selves.

According to the surgeons, their choices of actions and ways of being in relationships with patients and colleagues have to be accepted and confirmed by their inner moral selves. They speak about "having the courage of your own conviction", "taking a stand", "having a personal set of ethical values" as important in order to "live with" the ethical challenges of surgery. The surgeons in this study revealed their identities through their narratives about being in ethically difficult situations.

Being a surgeon means having the necessary specialized knowledge, skills, and experience to perform complicated, extensive, and technically advanced operations in principally uncertain and unpredictable situations. This identity is socially sustained through dialogues with patients, relatives, and colleagues. To have an identity as a surgeon is also to understand that one is vulnerable and exposed in these relationships and to know what is at stake in one's own life as well as in the lives of the patients and colleagues.

In this study uncertainty, fallibility, and humility seem to be equally important in the surgeons' identities as are their responsibility and confidence. The social importance and benefit of their work to patients and society is confirmed both socially and by their moral selves. This seems to outweigh their personal uncertainty and vulnerability. Thus, surgeons seem to appreciate their work and have learned to live with, and to a certain extent even appreciate, its most difficult dimensions. The meaning of being a surgeon is to be able to live with the tensions of contradictions, ambivalence, dilemmas, and paradoxes in their practice and to find workable solutions in these situations.

VS participated in the design of the study, read the interviews, participated in the analysis and helped to draft the manuscript.

All authors have read and approved the final manuscript.

Table 1 :
1Themes and subthemes that emerged from the structural analysis of interviews with the surgeons.meaningful life afterwards or leads to a life that would be experienced as a heavy burden". The surgeons said that they become personally involved with their patients, focusing on patients as persons and their quality of life as much as on their medical treatment. Being involved and knowing the patients' background and what they really want in life makes difficult ethical decisions easier to handle. The surgeons explained that caring for the patient can be felt as a personal, emotional burden. "It's not easy when people you have established a relationship with die. The only way to run away from it is to relinquish your responsibility. But that means disassociating yourself from or rejecting the patient. So you have to care, to be involved and to be a human being".Themes
Subthemes

Dialogue with patients
Openness and honesty
Involvement

Social confirmation
Professional recognition
Open dialogue

Self confirmation
Responsibility
Uncertainty
Fallibility
Confidence
Humility

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AcknowledgementsThis study was supported by Sør-Trøndelag University College, Faculty of Nursing, Norway. This study is part of a larger ethical project which includes studies from different medical specialties. The authors are grateful to the participants in the study and to Ms Jill Almvang, Fulbright Scholar Marjory Schaffer, University of Oslo and Assistant Professor Stewart Clark, Norwegian University of Science and Technology, Trondheim for the linguistic revision.Competing interestsThe author(s) declare that they have no competing interests.Authors' contributionsKT participated in the design of the study, carried out the interviews, participated in the analysis and completed the manuscript.AN read the interviews, participated in the analysis and helped to draft the manuscript.Pre-publication historyThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6939/6/2/prepub
Ethical reasoning in nurses' and physicians' stories about care episodes. G Udén, A Norberg, A Lindseth, V Marhaug, J Adv Nurs. 9Udén G, Norberg A, Lindseth A, Marhaug V: Ethical reasoning in nurses' and physicians' stories about care episodes. J Adv Nurs 1992, 9:1028-1034.

Ethics in research and surgical practice. D L Lasalle, Am J Surg. 6LaSalle DL: Ethics in research and surgical practice. Am J Surg 1997, 6:589-591.

L B Mccullough, J W Jones, B A Brody, Surgical Ethics. New York, OxfordOxford University PressMcCullough LB, Jones JW, Brody BA, Eds: Surgical Ethics New York, Oxford: Oxford University Press; 1998.

The role of caring in nursing ethics. In Quality development in nursing care. A Lindseth, University Health Service Studies. 1992Lindseth A: The role of caring in nursing ethics. In Quality devel- opment in nursing care. From practice to science Edited by: Udén G. Linköping: University Health Service Studies; 1992:97-106.

T L Beauchamp, J F Childress, Principles of biomedical ethics 5th edition. OxfordOxford University PressBeauchamp TL, Childress JF: Principles of biomedical ethics 5th edition. Oxford: Oxford University Press; 2001.

After Virtue -A study in moral theory 2nd edition. A Macintyre, Harvard University PressCambridge, Massachusetts and LondonMacIntyre A: After Virtue -A study in moral theory 2nd edition. Cam- bridge, Massachusetts and London: Harvard University Press; 2001.

The ethical foundational experience. From understanding rules to experiential knowledge Oslo: Universitetsforlaget AS. H Nerheim, in NorwegianNerheim H: The ethical foundational experience. From understanding rules to experiential knowledge Oslo: Universitetsforlaget AS; 1991. (in Norwegian)

Human values in the care of the surgical patient. L Peterson, Arch Surg. 1Peterson L: Human values in the care of the surgical patient. Arch Surg 2000, 1:46-50.

Ethical aspects of clinical practice. P L Nandi, Arch Surg. 1Nandi PL: Ethical aspects of clinical practice. Arch Surg 2000, 1:22-25.

Engagement and suffering in responsible caregiving: on overcoming maleficience in health care. D S Scultz, F A Carnevale, Theor Med. 3Scultz DS, Carnevale FA: Engagement and suffering in responsi- ble caregiving: on overcoming maleficience in health care. Theor Med 1996, 3:189-207.

The physician role in transition: is Hippocrates sick?. O G Aasland, Soc Sci Med. 2Aasland OG: The physician role in transition: is Hippocrates sick? Soc Sci Med 2001, 2:171-173.

Unhappy doctors: what are the causes and what can be done?. N Edwards, M J Kornacki, J Silversin, BMJ. 7341Edwards N, Kornacki MJ, Silversin J: Unhappy doctors: what are the causes and what can be done? BMJ 2002, 7341:835-838.

The stories of physicians, registered nurses and enrolled nurses about ethically difficult care episodes in surgical care. G Udén, A Norberg, S Norberg, Scand J Caring Sci. 4Udén G, Norberg A, Norberg S: The stories of physicians, regis- tered nurses and enrolled nurses about ethically difficult care episodes in surgical care. Scand J Caring Sci 1995, 4:245-253.

Declining altruism in medicine. R Jones, BMJ. 7338Jones R: Declining altruism in medicine. BMJ 2002, 7338:624-625. (March 16)

Ethics and philosophy lecture: surgery. Is it an impairing profession?. T Krizek, J Am Coll Surg. 3Krizek T: Ethics and philosophy lecture: surgery. Is it an impairing profession? J Am Coll Surg 2002, 3:352-366.

Psychosocial challenges facing physicians of today. B B Arnetz, Soc Sci Med. 2Arnetz BB: Psychosocial challenges facing physicians of today. Soc Sci Med 2001, 2:203-213.

Communicative competence in the delivery of bad news. C Gillotti, T Thomson, K Mcneilis, Soc Sci Med. 7Gillotti C, Thomson T, McNeilis K: Communicative competence in the delivery of bad news. Soc Sci Med 2002, 7:1011-1023.

The end of beneficience?. K Straume, Tidsskr Nor Laegeforen. 4in NorwegianStraume K: The end of beneficience? Tidsskr Nor Laegeforen 2001, 4:495-497. (in Norwegian)

K M Hunter, Doctors' stories. The narrative structure of medical knowledge Princetown. New JerseyPrincetown University PressHunter KM: Doctors' stories. The narrative structure of medical knowledge Princetown, New Jersey: Princetown University Press; 1991.

M M Rosenthal, L Mulcahy, S Lloyd-Bostock, Medical Mishaps. Pieces of the puzzle. Buckingham-PhiladelphiaOpen University PressRosenthal MM, Mulcahy L, Lloyd-Bostock S, Eds: Medical Mishaps. Pieces of the puzzle Buckingham-Philadelphia: Open University Press; 1999.

Forgive and remember. Managing medical failure Chicago and London: The University of. C L Bosk, Chicago PressBosk CL: Forgive and remember. Managing medical failure Chicago and London: The University of Chicago Press; 1979.

Why are doctors so unhappy?. R Smith, BMJ. 7294Smith R: Why are doctors so unhappy? BMJ 2001, 7294:1073-1074. (Jun 2)

Too much medicine?. R Moniham, R Smith, BMJ. 324Moniham R, Smith R: Too much medicine? BMJ 2002, 324:859-860. (April 13)

The collegial culture and "medical errors. R Førde, Medical errors Edited by: Syse A. Førde R, Førde OH. Osloin NorwegianFørde R: The collegial culture and "medical errors". In Medical errors Edited by: Syse A, Førde R, Førde OH. Oslo: Gyldendal Akademisk; 2000:183-194. (in Norwegian)

Ethics and evidence based surgery. G M Stirrat, J Med Ethics. 3Stirrat GM: Ethics and evidence based surgery. J Med Ethics 2004, 3:160-165.

Siegal I: Ethics and communication in the surgeon-patient relationship. M D Wertheimer, S L Bertman, H B Wheeler, J Med Educ. 10Wertheimer MD, Bertman SL, Wheeler HB, Siegal I: Ethics and communication in the surgeon-patient relationship. J Med Educ 1985, 10:804-806.

Living with conflicts -ethical dilemmas and moral distress in the health care system. S Kälvemark, A T Höglund, M G Hansson, P Westerholm, B Arnetz, Soc Sci Med. 6Kälvemark S, Höglund AT, Hansson MG, Westerholm P, Arnetz B: Living with conflicts -ethical dilemmas and moral distress in the health care system. Soc Sci Med 2004, 6:1075-1084.

On reflection: doctors learning to care for people who are dying. R D Macleod, Soc Sci Med. 11MacLeod RD: On reflection: doctors learning to care for peo- ple who are dying. Soc Sci Med 2001, 11:1719-1727.

Ethics in surgical practice. J M Little, Br J Surg. 6Little JM: Ethics in surgical practice. Br J Surg 2001, 6:769-770.

Women physicians' narratives about being in ethically difficult care situations in pediatrics. V Sørlie, A Lindseth, G Udén, A Norberg, Nurs Ethics. 1Sørlie V, Lindseth A, Udén G, Norberg A: Women physicians' nar- ratives about being in ethically difficult care situations in pediatrics. Nurs Ethics 2000, 1:47-62.

Integrity in the care of elderly people, as narrated by female physicians. A Nordam, V Sørlie, R Førde, Nurs Ethics. 4Nordam A, Sørlie V, Førde R: Integrity in the care of elderly peo- ple, as narrated by female physicians. Nurs Ethics 2003, 4:388-403.

Male physicians' narratives about being in ethically difficult care situations in paediatrics. V Sørlie, R Førde, A Lindseth, A Norberg, Soc Sci Med. 5Sørlie V, Førde R, Lindseth A, Norberg A: Male physicians' narra- tives about being in ethically difficult care situations in paediatrics. Soc Sci Med 2001, 5:657-667.

The threatened self: general practitioners' self-perception in relation to prescribing medicine. K Henriksen, E H Hansen, Soc Sci Med. 1Henriksen K, Hansen EH: The threatened self: general practi- tioners' self-perception in relation to prescribing medicine. Soc Sci Med 2004, 1:47-55.

Research interviewing -Context and narrative. E G Mishler, Harvard University PressCambridge, Massachusetts and LondonMishler EG: Research interviewing -Context and narrative Cambridge, Massachusetts and London: Harvard University Press; 1986.

Ricoeur P: Interpretation Theory. Discourse and the surplus of meaning Texas. Texas University PressRicoeur P: Interpretation Theory. Discourse and the surplus of meaning Texas: Texas University Press; 1976.

Registered nurses' and physicians' reflections on their narratives about ethically difficult care episodes. A Lindseth, V Marhaug, A Norberg, G Udén, J Adv Nurs. 2Lindseth A, Marhaug V, Norberg A, Udén G: Registered nurses' and physicians' reflections on their narratives about ethically difficult care episodes. J Adv Nurs 1994, 2:245-250.

Intensive care: situations of ethical difficulty. A Söderberg, A Norberg, J Adv Nurs. 12Söderberg A, Norberg A: Intensive care: situations of ethical difficulty. J Adv Nurs 1993, 12:2008-2014.

The meaning of being in ethically difficult care situations in pediatric care as narrated by female registered nurses. V Sørlie, L Jansson, A Norberg, Scand J Caring Sci. 3Sørlie V, Jansson L, Norberg A: The meaning of being in ethically difficult care situations in pediatric care as narrated by female registered nurses. Scand J Caring Sci 2003, 3:285-292.

A phenomenological hermeneutical method for researching lived experience. A Lindseth, A Norberg, Scand J Caring Sci. 2Lindseth A, Norberg A: A phenomenological hermeneutical method for researching lived experience. Scand J Caring Sci 2004, 2:145-53.

Oneself as another (French original 1990, Editions du Seuil). (English translation by Blamey K) Chicago and London. P Ricoeur, University of Chicago PressRicoeur P: Oneself as another (French original 1990, Editions du Seuil). (English translation by Blamey K) Chicago and London: University of Chicago Press; 1992.

Everyday Life Philosophers Norway: Universitetsforlaget. M Gullestad, Gullestad M: Everyday Life Philosophers Norway: Universitetsforlaget; 1996.

In this scenario, I do this, for this reason': narrative, genre and ethical reasoning in the clinic. C F Jordens, M Little, Soc Sci Med. 9Jordens CF, Little M: 'In this scenario, I do this, for this reason': narrative, genre and ethical reasoning in the clinic. Soc Sci Med 2004, 9:1635-45.

The ethical demand (Dan. Original 1956, Copenhagen, Gyldendal). (English translation by Jensen TI. K E Løgstrup, Philadelphia: Fortress PressLøgstrup KE: The ethical demand (Dan. Original 1956, Copenhagen, Gyldendal). (English translation by Jensen TI.) Philadelphia: Fortress Press; 1997.

Life itself -a life philosophical interpretation of Christian thoughts Århus, Denmark: Philosophia. M Pahuus, in DanishPahuus M: Life itself -a life philosophical interpretation of Christian thoughts Århus, Denmark: Philosophia; 1993. (in Danish)

Paternalism, patient autonomy, and moral deliberation in the physician -patient relationship. E Falkum, R Førde, Soc Sci Med. 2Falkum E, Førde R: Paternalism, patient autonomy, and moral deliberation in the physician -patient relationship. Soc Sci Med 2001, 2:239-248.

Closeness and Distance. Foundation, values and ethical theories in working with humans beings Oslo: Gyldendal Akademiske. J O Henriksen, A J Vetlesen, in NorwegianHenriksen JO, Vetlesen AJ: Closeness and Distance. Foundation, values and ethical theories in working with humans beings Oslo: Gyldendal Akademiske; 2000. (in Norwegian)

The world's classics. Aristotle , The Nicomachean ethics Oxford. Oxford University PressAristotle: The Nicomachean ethics Oxford: Oxford University Press. The world's classics; 1980.

Invitation to sociology. A humanistic perspective Great Britain: Penguin books. P Berger, Berger P: Invitation to sociology. A humanistic perspective Great Britain: Penguin books; 1983.

Am I still ethical? The socially-mediated process of nurses' moral identity. G A Doane, Nurs Ethics. 6Doane GA: Am I still ethical? The socially-mediated process of nurses' moral identity. Nurs Ethics 2002, 6:623-636.