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Published in: Langenbeck's Archives of Surgery 7/2010

01-09-2010 | Original Article

Diagnostic utility of immunohistochemical panel in various thyroid pathologies

Authors: Arturs Ozolins, Zenons Narbuts, Ilze Strumfa, Guna Volanska, Janis Gardovskis

Published in: Langenbeck's Archives of Surgery | Issue 7/2010

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Abstract

Background

For management of thyroid nodules, distinction between benign and malignant tumours is essential. The study was performed to evaluate the diagnostic value of molecular markers in different thyroid tumours.

Materials and methods

Immunohistochemistry for CD56, HBME-1, COX-2, Ki-67, p53 and E-cadherin (E-CAD) was performed in 113 benign and 35 malignant thyroid lesions including 36 follicular adenomas (FA), 77 colloid goitres, 26 papillary thyroid carcinomas (PTC) and 9 follicular carcinomas (FC). The results were scored semiquantitatively by staining intensity (0–3 scale) and percentage of positive cells.

Results

PTC was characterised by decreased E-CAD and CD56 expression in contrast to surrounding benign thyroid tissues. HBME-1 expression was absent in benign thyroid tissues but was notably high in PTC and occasionally in FC. The expression of E-CAD and CD56 in FA was significantly higher than in the surrounding thyroid tissues. No expression of p53 was found in any group. The expression of COX-2 was low in all lesions. The proliferation activity by Ki-67 was generally low; however, it was significantly higher in cancers.

Conclusions

The panel consisting of three markers, HBME-1, E-CAD and CD56, can be recommended as an adjunct to morphology criteria. HBME-1 is found in malignant lesions only and is the most sensitive and specific single marker in PTC. Decreased expression of E-CAD and CD56 distinguishes PTC from FA and FC. Both FA and FC are characterised by high expression of E-CAD and CD56. The practical use of Ki-67 is difficult due to low values. The role of adhesion factors in thyroid malignancies may be superior in comparison with cell proliferation.
Literature
1.
go back to reference Gharib H, Papini E (2007) Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin N Am 36:707–735CrossRef Gharib H, Papini E (2007) Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin N Am 36:707–735CrossRef
2.
go back to reference Topliss D (2004) Thyroid incidentaloma: the ignorant in pursuit of the impalpable. Clin Endocrinol (Oxf) 60:18–20CrossRef Topliss D (2004) Thyroid incidentaloma: the ignorant in pursuit of the impalpable. Clin Endocrinol (Oxf) 60:18–20CrossRef
3.
go back to reference Hundahl SA et al (1998) A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 83:2638–2648CrossRefPubMed Hundahl SA et al (1998) A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 83:2638–2648CrossRefPubMed
4.
go back to reference Finley DJ et al (2004) Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 89:3214–3223CrossRefPubMed Finley DJ et al (2004) Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 89:3214–3223CrossRefPubMed
5.
go back to reference Liu YY et al (2008) Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-{gamma}, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma. Eur J Endocrinol 158:375–384CrossRefPubMed Liu YY et al (2008) Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-{gamma}, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma. Eur J Endocrinol 158:375–384CrossRefPubMed
6.
go back to reference Haugen BR, Woodmansee WW, McDermott MT (2002) Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours. Clin Endocrinol (Oxf) 56:281–290CrossRef Haugen BR, Woodmansee WW, McDermott MT (2002) Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours. Clin Endocrinol (Oxf) 56:281–290CrossRef
7.
go back to reference Bancroft JD, Gamble M (2003) Theory and practice of histological techniques, international edition. Churchill Livingstone, Edinburgh Bancroft JD, Gamble M (2003) Theory and practice of histological techniques, international edition. Churchill Livingstone, Edinburgh
9.
go back to reference Altman DG, Machin D, Bryant TN, Gardner MJ (2005) Statistics with confidence, 2nd edn. BMJ, Bristol Altman DG, Machin D, Bryant TN, Gardner MJ (2005) Statistics with confidence, 2nd edn. BMJ, Bristol
10.
go back to reference Sheibani K et al (1992) Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol 23:107–116CrossRefPubMed Sheibani K et al (1992) Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol 23:107–116CrossRefPubMed
11.
go back to reference Saleh HA et al (2010) Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol 5:9CrossRefPubMed Saleh HA et al (2010) Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol 5:9CrossRefPubMed
12.
go back to reference Miettinen M, Karkkainen P (1996) Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity malignant tumours. Virchows Arch 429:213–219CrossRefPubMed Miettinen M, Karkkainen P (1996) Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity malignant tumours. Virchows Arch 429:213–219CrossRefPubMed
13.
go back to reference Sack MJ et al (1997) HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. Mod Pathol 10:668–674PubMed Sack MJ et al (1997) HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. Mod Pathol 10:668–674PubMed
14.
go back to reference Mai KT et al (2002) Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes. Histopathology 40:133–142CrossRefPubMed Mai KT et al (2002) Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes. Histopathology 40:133–142CrossRefPubMed
15.
go back to reference Ito Y et al (2005) HBME-1 expression in follicular tumor of the thyroid: an investigation of whether it can be used as a marker to diagnose follicular carcinoma. Anticancer Res 25:179–182PubMed Ito Y et al (2005) HBME-1 expression in follicular tumor of the thyroid: an investigation of whether it can be used as a marker to diagnose follicular carcinoma. Anticancer Res 25:179–182PubMed
16.
go back to reference Papotti M et al (2005) Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 18:541–546CrossRefPubMed Papotti M et al (2005) Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 18:541–546CrossRefPubMed
17.
go back to reference Prasad ML et al (2005) Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57CrossRefPubMed Prasad ML et al (2005) Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57CrossRefPubMed
18.
go back to reference Rossi ED et al (2006) Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid. Histopathology 48:795–800CrossRefPubMed Rossi ED et al (2006) Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid. Histopathology 48:795–800CrossRefPubMed
19.
go back to reference Saggiorato E et al (2005) Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer 12:305–317CrossRefPubMed Saggiorato E et al (2005) Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer 12:305–317CrossRefPubMed
20.
go back to reference de Micco et al (2008) Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV. Br J Cancer 98:818–823CrossRefPubMed de Micco et al (2008) Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV. Br J Cancer 98:818–823CrossRefPubMed
21.
go back to reference Nasr MR et al (2006) Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME1 combined with CK19 immunostaining. Mod Pathol 19:1631–1637CrossRefPubMed Nasr MR et al (2006) Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME1 combined with CK19 immunostaining. Mod Pathol 19:1631–1637CrossRefPubMed
22.
go back to reference Saleh HA et al (2009) Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cytojournal 6:18CrossRefPubMed Saleh HA et al (2009) Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cytojournal 6:18CrossRefPubMed
23.
go back to reference Nga ME et al (2008) HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma. Diagn Cytopathol 36:550–556CrossRefPubMed Nga ME et al (2008) HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma. Diagn Cytopathol 36:550–556CrossRefPubMed
24.
go back to reference Scognamiglio T et al (2006) Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol 126:700–708CrossRefPubMed Scognamiglio T et al (2006) Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol 126:700–708CrossRefPubMed
25.
go back to reference Mase T et al (2003) HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 50:173–177CrossRefPubMed Mase T et al (2003) HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 50:173–177CrossRefPubMed
26.
go back to reference Park YJ et al (2007) Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules. J Korean Med Sci 22:621–628CrossRefPubMed Park YJ et al (2007) Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules. J Korean Med Sci 22:621–628CrossRefPubMed
27.
go back to reference Zeromski J et al (1992) Expression of CD56 (NKH-1) differentiation antigen in human thyroid epithelium. Clin Exp Immunol 89:474–478CrossRefPubMed Zeromski J et al (1992) Expression of CD56 (NKH-1) differentiation antigen in human thyroid epithelium. Clin Exp Immunol 89:474–478CrossRefPubMed
28.
go back to reference El Demellawy D, Nasr A, Alowami S (2009) An updated review on the clinicopathologic aspects of arrhythmogenic right ventricular cardiomyopathy. Am J Forensic Med Pathol 30:78–83CrossRefPubMed El Demellawy D, Nasr A, Alowami S (2009) An updated review on the clinicopathologic aspects of arrhythmogenic right ventricular cardiomyopathy. Am J Forensic Med Pathol 30:78–83CrossRefPubMed
29.
go back to reference El Demellawy D, Nasr A, Alowami S (2008) Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid. Diagn Pathol 3:5CrossRefPubMed El Demellawy D, Nasr A, Alowami S (2008) Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid. Diagn Pathol 3:5CrossRefPubMed
30.
go back to reference Scarpino S et al (2007) Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells. J Pathol 212:411–419CrossRefPubMed Scarpino S et al (2007) Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells. J Pathol 212:411–419CrossRefPubMed
31.
go back to reference Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575–581CrossRefPubMed Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575–581CrossRefPubMed
32.
go back to reference Eidelman S et al (1989) Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors. Am J Pathol 135:101–110PubMed Eidelman S et al (1989) Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors. Am J Pathol 135:101–110PubMed
33.
go back to reference Brabant G et al (1993) E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res 53:4987–4993PubMed Brabant G et al (1993) E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res 53:4987–4993PubMed
34.
go back to reference Soares P et al (1997) E-cadherin gene alterations are rare events in thyroid tumors. Int J Cancer 70:32–38CrossRefPubMed Soares P et al (1997) E-cadherin gene alterations are rare events in thyroid tumors. Int J Cancer 70:32–38CrossRefPubMed
35.
go back to reference von Wasielewski R et al (1997) Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas correlates with clinical outcome. Cancer Res 57:2501–2507 von Wasielewski R et al (1997) Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas correlates with clinical outcome. Cancer Res 57:2501–2507
36.
go back to reference Graff JR et al (1998) Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle's cell, and poorly differentiated human thyroid carcinoma. Cancer Res 58:2063–2066PubMed Graff JR et al (1998) Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle's cell, and poorly differentiated human thyroid carcinoma. Cancer Res 58:2063–2066PubMed
37.
go back to reference Choi YL et al (2005) Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci 20:853–859CrossRefPubMed Choi YL et al (2005) Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas. J Korean Med Sci 20:853–859CrossRefPubMed
38.
go back to reference Smyth P et al (2001) Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms. Int J Surg Pathol 9:265–272CrossRefPubMed Smyth P et al (2001) Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms. Int J Surg Pathol 9:265–272CrossRefPubMed
39.
go back to reference Fosslien E (2000) Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30:3–21PubMed Fosslien E (2000) Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30:3–21PubMed
40.
41.
go back to reference Specht MC et al (2002) Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 87:358–363CrossRefPubMed Specht MC et al (2002) Cyclooxygenase-2 expression in thyroid nodules. J Clin Endocrinol Metab 87:358–363CrossRefPubMed
42.
go back to reference Casey MB et al (2004) Expression of cyclooxygenase-2 and thromboxane synthase in non-neoplastic and neoplastic thyroid lesions. Endocr Pathol 15:107–116CrossRefPubMed Casey MB et al (2004) Expression of cyclooxygenase-2 and thromboxane synthase in non-neoplastic and neoplastic thyroid lesions. Endocr Pathol 15:107–116CrossRefPubMed
43.
go back to reference Cornetta AJ et al (2002) Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis. Laryngoscope 112:238–242CrossRefPubMed Cornetta AJ et al (2002) Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis. Laryngoscope 112:238–242CrossRefPubMed
44.
go back to reference Kim SJ et al (2003) Immunohistochemical expression of COX-2 in thyroid nodules. Korean J Intern Med 18:225–229PubMed Kim SJ et al (2003) Immunohistochemical expression of COX-2 in thyroid nodules. Korean J Intern Med 18:225–229PubMed
45.
go back to reference Nose F et al (2002) Up-regulation of cyclooxygenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase. Am J Clin Pathol 117:546–551CrossRefPubMed Nose F et al (2002) Up-regulation of cyclooxygenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase. Am J Clin Pathol 117:546–551CrossRefPubMed
46.
go back to reference Haynik DM, Prayson RA (2005) Immunohistochemical expression of cyclooxygenase 2 in follicular carcinomas of the thyroid. Arch Pathol Lab Med 129:736–741PubMed Haynik DM, Prayson RA (2005) Immunohistochemical expression of cyclooxygenase 2 in follicular carcinomas of the thyroid. Arch Pathol Lab Med 129:736–741PubMed
47.
go back to reference Saad AG et al (2006) Proliferative activity of human thyroid cells in various age groups and its correlation with the risk of thyroid cancer after radiation exposure. J Clin Endocrinol Metab 91:2672–2677CrossRefPubMed Saad AG et al (2006) Proliferative activity of human thyroid cells in various age groups and its correlation with the risk of thyroid cancer after radiation exposure. J Clin Endocrinol Metab 91:2672–2677CrossRefPubMed
48.
go back to reference Ziad el A et al (2008) Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving. Folia Histochem Cytobiol 46:461–464CrossRefPubMed Ziad el A et al (2008) Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving. Folia Histochem Cytobiol 46:461–464CrossRefPubMed
49.
go back to reference Novosel I et al (2006) p53, bcl-2 and Ki-67 in the diagnosis of insular thyroid gland cancer. Case report with a review of literature. Lijec Vjesn 128:264–267PubMed Novosel I et al (2006) p53, bcl-2 and Ki-67 in the diagnosis of insular thyroid gland cancer. Case report with a review of literature. Lijec Vjesn 128:264–267PubMed
50.
go back to reference Akslen LA, Varhaug JE (1995) Oncoproteins and tumor progression in papillary thyroid carcinoma: presence of epidermal growth factor receptor, c-erbB-2 protein, estrogen receptor related protein, p21-ras protein, and proliferation indicators in relation to tumor recurrences and patient survival. Cancer 76:1643–1654CrossRefPubMed Akslen LA, Varhaug JE (1995) Oncoproteins and tumor progression in papillary thyroid carcinoma: presence of epidermal growth factor receptor, c-erbB-2 protein, estrogen receptor related protein, p21-ras protein, and proliferation indicators in relation to tumor recurrences and patient survival. Cancer 76:1643–1654CrossRefPubMed
51.
go back to reference Martinez J, Georgoff I, Levine AJ (1991) Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev 5:151–159CrossRefPubMed Martinez J, Georgoff I, Levine AJ (1991) Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev 5:151–159CrossRefPubMed
52.
go back to reference Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093CrossRefPubMed Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093CrossRefPubMed
53.
go back to reference Morita N, Ikeda Y, Takami H (2008) Clinical significance of p53 protein expression in papillary thyroid carcinoma. World J Surg 32:2617–2622CrossRefPubMed Morita N, Ikeda Y, Takami H (2008) Clinical significance of p53 protein expression in papillary thyroid carcinoma. World J Surg 32:2617–2622CrossRefPubMed
54.
go back to reference Dobashi Y et al (1993) Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma. Am J Surg Pathol 17:375–381CrossRefPubMed Dobashi Y et al (1993) Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma. Am J Surg Pathol 17:375–381CrossRefPubMed
55.
go back to reference Chen BK et al (1999) Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage. Int J Oncol 15:893–898PubMed Chen BK et al (1999) Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage. Int J Oncol 15:893–898PubMed
56.
go back to reference Kobayashi T et al (1995) Clinicopathological findings and p53 expression of thyroid cancer in children. Surg Today 25:217–221CrossRefPubMed Kobayashi T et al (1995) Clinicopathological findings and p53 expression of thyroid cancer in children. Surg Today 25:217–221CrossRefPubMed
Metadata
Title
Diagnostic utility of immunohistochemical panel in various thyroid pathologies
Authors
Arturs Ozolins
Zenons Narbuts
Ilze Strumfa
Guna Volanska
Janis Gardovskis
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
Langenbeck's Archives of Surgery / Issue 7/2010
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-010-0690-6

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