Skip to main content
Erschienen in: Clinical Orthopaedics and Related Research® 6/2014

01.06.2014 | Clinical Research

Proximal Tumor Location and Fluid-fluid Levels on MRI Predict Resistance to Chemotherapy in Stage IIB Osteosarcoma

verfasst von: Dae-Geun Jeon, MD, Won Seok Song, MD, Wan Hyeong Cho, MD, Chang-Bae Kong, MD, Sang Hyun Cho, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Primary tumor growth during neoadjuvant chemotherapy is believed to be a sign of resistance to chemotherapy (chemoresistance), and often is associated with poor histologic response, local recurrence, and poorer survival. Currently there are no proven indicators to predict poor response to chemotherapy at the time of diagnosis.

Questions/purposes

We asked (1) what clinicopathologic factors present at diagnosis predict primary tumor growth during neoadjuvant chemotherapy, (2) what factors at presentation predict survival, and (3) when the factors at presentation and the treatment-related factors are considered, what factors independently correlate with survival.

Methods

We studied 567 patients with Stage IIB osteosarcomas. The factors assessed included age, sex, location, pattern on plain radiographs (radiodense, radiolucent, mixed), MRI findings, pathologic subtype, initial tumor volume determined by MRI, tumor volume change after chemotherapy, surgical margin, and histologic response to preoperative chemotherapy. Logistic modeling was used to identify risk factors.

Results

Independent risk factors associated with primary tumor growth after neoadjuvant chemotherapy were proximal tumor location (p < 0.01; relative risk [RR], 2.41; 95% CI, 1.5–3.86) and fluid-fluid level on initial MRI (p < 0.01; RR, 5.56; 95% CI, 3.48–8.87). Among factors at presentation, large initial tumor volume (p < 0.01; RR, 1.58; 95% CI, 1.22–2.04), proximal tumor site (p < 0.01; RR, 1.61; 95% CI, 1.19–2.19), and presence of fluid-fluid level (p < 0.01; RR, 1.83; 95% CI, 1.37–2.5) independently predicted reduced event–free survival. When we consider the factors at presentation and treatment-related factors, large initial tumor volume (p < 0.01; RR, 1.54), tumor growth after neoadjuvant chemotherapy (p < 0.01; RR, 3.88), inadequate surgical margin (p < 0.01; RR, 2.42), and poor histologic response (p = 0.03; RR, 1.43) were independent poor prognostic factors of event-free survival.

Conclusions

Proximal tumor location and the presence of the fluid-fluid level on initial MRI were predictors of tumor progression and poor survival in patients presenting with Stage IIB osteosarcomas. If confirmed in other studies, patients with these risk factors should be considered for trials of other treatment strategy.

Level of Evidence

Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
Literatur
1.
Zurück zum Zitat Bacci G, Bertoni F, Longhi A, Ferrari S, Forni C, Biagini R, Bacchini P, Donati D, Manfrini M, Bernini G, Lari S. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity: histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer. 2003;97:3068–3075.PubMedCrossRef Bacci G, Bertoni F, Longhi A, Ferrari S, Forni C, Biagini R, Bacchini P, Donati D, Manfrini M, Bernini G, Lari S. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity: histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer. 2003;97:3068–3075.PubMedCrossRef
2.
Zurück zum Zitat Bacci G, Ferrari S, Ruggieri P, Biagini R, Fabbri N, Campanacci L, Bacchini P, Longhi A, Forni C, Bertoni F. Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases. Acta Orthop Scand. 2001;72:167–172.PubMedCrossRef Bacci G, Ferrari S, Ruggieri P, Biagini R, Fabbri N, Campanacci L, Bacchini P, Longhi A, Forni C, Bertoni F. Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases. Acta Orthop Scand. 2001;72:167–172.PubMedCrossRef
3.
Zurück zum Zitat Bacci G, Mercuri M, Longhi A, Ferrari S, Bertoni F, Versari M, Picci P. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution. Eur J Cancer. 2005;41:2079–2085.PubMedCrossRef Bacci G, Mercuri M, Longhi A, Ferrari S, Bertoni F, Versari M, Picci P. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution. Eur J Cancer. 2005;41:2079–2085.PubMedCrossRef
4.
Zurück zum Zitat Bacci G, Picci P, Ferrari S, Orlandi M, Ruggieri P, Casadei R, Ferraro A, Biagini R, Battistini A. Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy. Cancer. 1993;71:1224–1230.PubMedCrossRef Bacci G, Picci P, Ferrari S, Orlandi M, Ruggieri P, Casadei R, Ferraro A, Biagini R, Battistini A. Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy. Cancer. 1993;71:1224–1230.PubMedCrossRef
5.
Zurück zum Zitat Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jurgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–790.PubMedCrossRef Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jurgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–790.PubMedCrossRef
6.
Zurück zum Zitat Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol. 1996;14:848–858.PubMed Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol. 1996;14:848–858.PubMed
7.
Zurück zum Zitat Briccoli A, Rocca M, Salone M, Bacci G, Ferrari S, Balladelli A, Mercuri M. Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer. 2005;104:1721–1725.PubMedCrossRef Briccoli A, Rocca M, Salone M, Bacci G, Ferrari S, Balladelli A, Mercuri M. Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer. 2005;104:1721–1725.PubMedCrossRef
8.
Zurück zum Zitat Cho WH, Song WS, Jeon DG, Kong CB, Kim MS, Lee JA, Yoo JY, Kim JD, Lee SY. Differential presentations, clinical courses, and survivals of osteosarcomas of the proximal humerus over other extremity locations. Ann Surg Oncol. 2010;17:702–708.PubMedCrossRef Cho WH, Song WS, Jeon DG, Kong CB, Kim MS, Lee JA, Yoo JY, Kim JD, Lee SY. Differential presentations, clinical courses, and survivals of osteosarcomas of the proximal humerus over other extremity locations. Ann Surg Oncol. 2010;17:702–708.PubMedCrossRef
9.
Zurück zum Zitat Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–431.PubMed Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–431.PubMed
10.
Zurück zum Zitat Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153:106–120.PubMed Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153:106–120.PubMed
11.
Zurück zum Zitat Fellenberg J, Dechant MJ, Ewerbeck V, Mau H. Identification of drug-regulated genes in osteosarcoma cells. Int J Cancer. 2003;105:636–643.PubMedCrossRef Fellenberg J, Dechant MJ, Ewerbeck V, Mau H. Identification of drug-regulated genes in osteosarcoma cells. Int J Cancer. 2003;105:636–643.PubMedCrossRef
12.
Zurück zum Zitat Fuchs N, Bielack SS, Epler D, Bieling P, Delling G, Korholz D, Graf N, Heise U, Jurgens H, Kotz R, Salzer-Kuntschik M, Weinel P, Werner M, Winkler K. Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol. 1998;9:893–899.PubMedCrossRef Fuchs N, Bielack SS, Epler D, Bieling P, Delling G, Korholz D, Graf N, Heise U, Jurgens H, Kotz R, Salzer-Kuntschik M, Weinel P, Werner M, Winkler K. Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol. 1998;9:893–899.PubMedCrossRef
13.
Zurück zum Zitat Gobel V, Jurgens H, Etspuler G, Kemperdick H, Jungblut RM, Stienen U, Gobel U. Prognostic significance of tumor volume in localized Ewing’s sarcoma of bone in children and adolescents. J Cancer Res Clin Oncol. 1987;113:187–191.PubMedCrossRef Gobel V, Jurgens H, Etspuler G, Kemperdick H, Jungblut RM, Stienen U, Gobel U. Prognostic significance of tumor volume in localized Ewing’s sarcoma of bone in children and adolescents. J Cancer Res Clin Oncol. 1987;113:187–191.PubMedCrossRef
14.
Zurück zum Zitat Harting MT, Lally KP, Andrassy RJ, Vaporciyan AA, Cox CS Jr, Hayes-Jordan A, Blakely ML. Age as a prognostic factor for patients with osteosarcoma: an analysis of 438 patients. J Cancer Res Clin Oncol. 2010;136:561–570.PubMedCrossRef Harting MT, Lally KP, Andrassy RJ, Vaporciyan AA, Cox CS Jr, Hayes-Jordan A, Blakely ML. Age as a prognostic factor for patients with osteosarcoma: an analysis of 438 patients. J Cancer Res Clin Oncol. 2010;136:561–570.PubMedCrossRef
15.
Zurück zum Zitat Holscher HC, Bloem JL, Vanel D, Hermans J, Nooy MA, Taminiau AH, Henry-Amar M. Osteosarcoma: chemotherapy-induced changes at MR imaging. Radiology. 1992;182:839–844.PubMed Holscher HC, Bloem JL, Vanel D, Hermans J, Nooy MA, Taminiau AH, Henry-Amar M. Osteosarcoma: chemotherapy-induced changes at MR imaging. Radiology. 1992;182:839–844.PubMed
16.
Zurück zum Zitat Ifergan I, Meller I, Issakov J, Assaraf YG. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer. 2003;98:1958–1966.PubMedCrossRef Ifergan I, Meller I, Issakov J, Assaraf YG. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer. 2003;98:1958–1966.PubMedCrossRef
17.
Zurück zum Zitat Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM, Helman LJ. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10:182–186.PubMedCrossRef Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM, Helman LJ. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10:182–186.PubMedCrossRef
18.
Zurück zum Zitat Kim MS, Cho WH, Song WS, Lee SY, Jeon DG. time dependency of prognostic factors in patients with stage II osteosarcomas. Clin Orthop Relat Res. 2007;463:157–165.PubMed Kim MS, Cho WH, Song WS, Lee SY, Jeon DG. time dependency of prognostic factors in patients with stage II osteosarcomas. Clin Orthop Relat Res. 2007;463:157–165.PubMed
19.
Zurück zum Zitat Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jung ST, Jeon DG. Relationships between plain-film radiographic patterns and clinicopathologic variables in AJCC stage II osteosarcoma. Skeletal Radiol. 2008;37:997–1001.PubMedCrossRef Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jung ST, Jeon DG. Relationships between plain-film radiographic patterns and clinicopathologic variables in AJCC stage II osteosarcoma. Skeletal Radiol. 2008;37:997–1001.PubMedCrossRef
20.
Zurück zum Zitat Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jung ST, Jeon DG. Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response. J Orthop Sci. 2009;14:292–297.PubMedCrossRef Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jung ST, Jeon DG. Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response. J Orthop Sci. 2009;14:292–297.PubMedCrossRef
21.
Zurück zum Zitat Kong CB, Song WS, Cho WH, Oh JM, Jeon DG. Local recurrence has only a small effect on survival in high-risk extremity osteosarcoma. Clin Orthop Relat Res. 2012;470:1482–1490.PubMedCentralPubMedCrossRef Kong CB, Song WS, Cho WH, Oh JM, Jeon DG. Local recurrence has only a small effect on survival in high-risk extremity osteosarcoma. Clin Orthop Relat Res. 2012;470:1482–1490.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Lee SY, Jeon DG, Cho WH, Song WS, Kim MB, Park JH. Preliminary study of chemosenstivity tests in osteosarcoma using a histoculture drug response assay. Anticancer Res. 2006;26:2929–2932.PubMed Lee SY, Jeon DG, Cho WH, Song WS, Kim MB, Park JH. Preliminary study of chemosenstivity tests in osteosarcoma using a histoculture drug response assay. Anticancer Res. 2006;26:2929–2932.PubMed
23.
Zurück zum Zitat Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, Applewhite A, Vlamis V, Rosen G. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol. 1992;10:5–15.PubMed Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, Applewhite A, Vlamis V, Rosen G. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol. 1992;10:5–15.PubMed
24.
Zurück zum Zitat Picci P, Bacci G, Campanacci M, Gasparini M, Pilotti S, Cerasoli S, Bertoni F, Guerra A, Capanna R, Albisinni U, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy: regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–1521.PubMedCrossRef Picci P, Bacci G, Campanacci M, Gasparini M, Pilotti S, Cerasoli S, Bertoni F, Guerra A, Capanna R, Albisinni U, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy: regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–1521.PubMedCrossRef
25.
Zurück zum Zitat Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, Huvos AG, Betcher DL, Baum ES, Kisker CT, Miser JS. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol. 1997;15:76–84.PubMed Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, Huvos AG, Betcher DL, Baum ES, Kisker CT, Miser JS. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol. 1997;15:76–84.PubMed
26.
Zurück zum Zitat Rosen G, Marcove RC, Huvos AG, Caparros BI, Lane JM, Nirenberg A, Cacavio A, Groshen S. Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy. J Cancer Res Clin Oncol. 1983;106(suppl):55–67.PubMedCrossRef Rosen G, Marcove RC, Huvos AG, Caparros BI, Lane JM, Nirenberg A, Cacavio A, Groshen S. Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy. J Cancer Res Clin Oncol. 1983;106(suppl):55–67.PubMedCrossRef
27.
Zurück zum Zitat Serra M, Picci P, Ferrari S, Bacci G. Prognostic value of P-glycoprotein in high-grade osteosarcoma. J Clin Oncol. 2007;25:4858–4860; author reply 4860–4861. Serra M, Picci P, Ferrari S, Bacci G. Prognostic value of P-glycoprotein in high-grade osteosarcoma. J Clin Oncol. 2007;25:4858–4860; author reply 4860–4861.
28.
Zurück zum Zitat Shin KH, Moon SH, Suh JS, Yang WI. Tumor volume change as a predictor of chemotherapeutic response in osteosarcoma. Clin Orthop Relat Res. 2000;376:200–208.PubMedCrossRef Shin KH, Moon SH, Suh JS, Yang WI. Tumor volume change as a predictor of chemotherapeutic response in osteosarcoma. Clin Orthop Relat Res. 2000;376:200–208.PubMedCrossRef
29.
Zurück zum Zitat Song WS, Cho WH, Jeon DG, Kong CB, Kim MS, Lee JA, Eid AS, Kim JD, Lee SY. Pelvis and extremity osteosarcoma with similar tumor volume have an equivalent survival. J Surg Oncol. 2010;101:611–617.PubMedCrossRef Song WS, Cho WH, Jeon DG, Kong CB, Kim MS, Lee JA, Eid AS, Kim JD, Lee SY. Pelvis and extremity osteosarcoma with similar tumor volume have an equivalent survival. J Surg Oncol. 2010;101:611–617.PubMedCrossRef
30.
Zurück zum Zitat Song WS, Jeon DG, Kong CB, Cho WH, Koh JS, Lee JA, Yoo JY, Jung ST, Shin DS, Lee SY. Tumor volume increase during preoperative chemotherapy as a novel predictor of local recurrence in extremity osteosarcoma. Ann Surg Oncol. 2011;18:1710–1716.PubMedCrossRef Song WS, Jeon DG, Kong CB, Cho WH, Koh JS, Lee JA, Yoo JY, Jung ST, Shin DS, Lee SY. Tumor volume increase during preoperative chemotherapy as a novel predictor of local recurrence in extremity osteosarcoma. Ann Surg Oncol. 2011;18:1710–1716.PubMedCrossRef
31.
Zurück zum Zitat Suresh S, Saifuddin A. Radiological appearances of appendicular osteosarcoma: a comprehensive pictorial review. Clin Radiol. 2007;62:314–323.PubMedCrossRef Suresh S, Saifuddin A. Radiological appearances of appendicular osteosarcoma: a comprehensive pictorial review. Clin Radiol. 2007;62:314–323.PubMedCrossRef
32.
Zurück zum Zitat Wunder JS, Gokgoz N, Parkes R, Bull SB, Eskandarian S, Davis AM, Beauchamp CP, Conrad EU, Grimer RJ, Healey JH, Malkin D, Mangham DC, Rock MJ, Bell RS, Andrulis IL. TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol. 2005;23:1483–1490.PubMedCrossRef Wunder JS, Gokgoz N, Parkes R, Bull SB, Eskandarian S, Davis AM, Beauchamp CP, Conrad EU, Grimer RJ, Healey JH, Malkin D, Mangham DC, Rock MJ, Bell RS, Andrulis IL. TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol. 2005;23:1483–1490.PubMedCrossRef
Metadaten
Titel
Proximal Tumor Location and Fluid-fluid Levels on MRI Predict Resistance to Chemotherapy in Stage IIB Osteosarcoma
verfasst von
Dae-Geun Jeon, MD
Won Seok Song, MD
Wan Hyeong Cho, MD
Chang-Bae Kong, MD
Sang Hyun Cho, MD
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Clinical Orthopaedics and Related Research® / Ausgabe 6/2014
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-014-3521-1

Weitere Artikel der Ausgabe 6/2014

Clinical Orthopaedics and Related Research® 6/2014 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.