Skip to main content
Erschienen in: Annals of Surgical Oncology 12/2012

01.11.2012 | Head and Neck Oncology

Intraoperative Molecular Assessment for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma Using One-Step Nucleic Acid Amplification (OSNA) Assay

verfasst von: Takashi Matsuzuka, MD, PhD, Katsumasa Takahashi, MD, PhD, Daisuke Kawakita, MD, PhD, Naoyuki Kohno, MD, PhD, Hiroshi Nagafuji, MD, Koichi Yamauchi, MD, PhD, Masahiro Suzuki, MD, Tomohiro Miura, MD, PhD, Nobuhiko Furuya, MD, PhD, Yasushi Yatabe, MD, PhD, Keitaro Matsuo, MD, PhD, MSc, Koichi Omori, MD, PhD, Yasuhisa Hasegawa, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 12/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Conventional intraoperative pathological examination for Sentinel node navigation surgery (SNNS) has been controversial. We evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of cervical lymph node (CLN) metastasis compared with histopathological examination in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 175 CLNs dissected from 56 patients with HNSCC who underwent surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima Medical University, between April 2008 and December 2011 were enrolled. CLN samples were sectioned into four equal pieces, with two of each used for OSNA assay and other histopathological examinations. The diagnostic value of OSNA assay in HNSCC patients in predicting the results of histopathological diagnosis was evaluated using the area under the receiver operating characteristic (AUROC) curve.

Results

OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95 % confidence interval [CI] 0.852–0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131 copies/μl (sensitivity: 82.4, 95 % CI 65.5–93.2; specificity: 99.3, 95 % CI 96.1–100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2].

Conclusions

We demonstrated that OSNA assay is useful in intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay could be applied for SNNS in HNSCC patients.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Murer K, Huber GF, Haile SR, Stoeckli SJ. Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma. Head Neck. 2011;33:1260–4.PubMedCrossRef Murer K, Huber GF, Haile SR, Stoeckli SJ. Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma. Head Neck. 2011;33:1260–4.PubMedCrossRef
2.
Zurück zum Zitat Alkureishi LW, Ross GL, Shoaib T, Soutar DS, Robertson AG, Thompson R, et al. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial. Ann Surg Oncol. 2010;17:2459–64.PubMedCrossRef Alkureishi LW, Ross GL, Shoaib T, Soutar DS, Robertson AG, Thompson R, et al. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial. Ann Surg Oncol. 2010;17:2459–64.PubMedCrossRef
3.
Zurück zum Zitat Kohno N, Ohno Y, Kihara K, Kitahara S, Tamura E, Tanabe T, et al. Feasibility of sentinel lymph node radiolocalization in neck node-negative oral squamous cell carcinoma patients. ORL J Otorhinolaryngol Relat Spec. 2003;65:66–70.PubMedCrossRef Kohno N, Ohno Y, Kihara K, Kitahara S, Tamura E, Tanabe T, et al. Feasibility of sentinel lymph node radiolocalization in neck node-negative oral squamous cell carcinoma patients. ORL J Otorhinolaryngol Relat Spec. 2003;65:66–70.PubMedCrossRef
4.
Zurück zum Zitat Kosuda S, Kusano S, Kohno N, Ohno Y, Tanabe T, Kitahara S, et al. Feasibility and cost-effectiveness of sentinel lymph node radiolocalization in stage N0 head and neck cancer. Arch Otolaryngol Head Neck Surg. 2003;129:1105–9.PubMedCrossRef Kosuda S, Kusano S, Kohno N, Ohno Y, Tanabe T, Kitahara S, et al. Feasibility and cost-effectiveness of sentinel lymph node radiolocalization in stage N0 head and neck cancer. Arch Otolaryngol Head Neck Surg. 2003;129:1105–9.PubMedCrossRef
5.
Zurück zum Zitat Matsuzuka T, Kano M, Ohtani I, Miura T, Shishido F, Omori K. Impact of sentinel node navigation technique for carcinoma of tongue with cervical node metastases. Auris Nasus Larynx. 2005;32:59–63.PubMedCrossRef Matsuzuka T, Kano M, Ohtani I, Miura T, Shishido F, Omori K. Impact of sentinel node navigation technique for carcinoma of tongue with cervical node metastases. Auris Nasus Larynx. 2005;32:59–63.PubMedCrossRef
6.
Zurück zum Zitat Terada A, Hasegawa Y, Goto M, Sato E, Hyodo I, Ogawa T, et al. Sentinel lymph node radiolocalization in clinically negative neck oral cancer. Head Neck. 2006;28:114–20.PubMedCrossRef Terada A, Hasegawa Y, Goto M, Sato E, Hyodo I, Ogawa T, et al. Sentinel lymph node radiolocalization in clinically negative neck oral cancer. Head Neck. 2006;28:114–20.PubMedCrossRef
7.
Zurück zum Zitat Matsuzuka T, Kano M, Ogawa H, Miura T, Tada Y, Matsui T, et al. Sentinel node mapping for node positive oral cancer: potential to predict multiple metastasis. Laryngoscope. 2008;118:646–9.PubMedCrossRef Matsuzuka T, Kano M, Ogawa H, Miura T, Tada Y, Matsui T, et al. Sentinel node mapping for node positive oral cancer: potential to predict multiple metastasis. Laryngoscope. 2008;118:646–9.PubMedCrossRef
8.
Zurück zum Zitat Terada A, Hasegawa Y, Yatabe Y, Hyodo I, Ogawa T, Hanai N, et al. Intraoperative diagnosis of cancer metastasis in sentinel lymph node of oral cancer patients. Oral Oncol. 2008;44:838–43.PubMedCrossRef Terada A, Hasegawa Y, Yatabe Y, Hyodo I, Ogawa T, Hanai N, et al. Intraoperative diagnosis of cancer metastasis in sentinel lymph node of oral cancer patients. Oral Oncol. 2008;44:838–43.PubMedCrossRef
9.
Zurück zum Zitat Terada A, Hasegawa Y, Yatabe Y, Hanai N, Ozawa T, Hirakawa H, et al. Follow-up after intraoperative sentinel node biopsy of N0 neck oral cancer patients. Eur Arch Otorhinolaryngol. 2011;268:429–35.PubMedCrossRef Terada A, Hasegawa Y, Yatabe Y, Hanai N, Ozawa T, Hirakawa H, et al. Follow-up after intraoperative sentinel node biopsy of N0 neck oral cancer patients. Eur Arch Otorhinolaryngol. 2011;268:429–35.PubMedCrossRef
10.
Zurück zum Zitat Yamauchi K, Fujioka Y, Kohno N. Sentinel node navigation surgery versus observation as a management strategy for early tongue carcinoma. Head Neck. 2012;34:568–72.PubMedCrossRef Yamauchi K, Fujioka Y, Kohno N. Sentinel node navigation surgery versus observation as a management strategy for early tongue carcinoma. Head Neck. 2012;34:568–72.PubMedCrossRef
11.
Zurück zum Zitat Yoshimoto S, Hasegawa Y, Matsuzuka T, Shiotani A, Takahashi K, Kohno N, et al. Sentinel node biopsy for oral and laryngopharyngeal squamous cell carcinoma: a retrospective study of 177 patients in Japan. Auris Nasus Larynx. 2012;39:65–70.PubMedCrossRef Yoshimoto S, Hasegawa Y, Matsuzuka T, Shiotani A, Takahashi K, Kohno N, et al. Sentinel node biopsy for oral and laryngopharyngeal squamous cell carcinoma: a retrospective study of 177 patients in Japan. Auris Nasus Larynx. 2012;39:65–70.PubMedCrossRef
12.
Zurück zum Zitat Ross GL, Soutar DS, Gordon MacDonald D, Shoaib T, Camilleri I, Roberton AG, et al. Sentinel node biopsy in head and neck cancer: preliminary results of a multicenter trial. Ann Surg Oncol. 2004;11:690–6.PubMedCrossRef Ross GL, Soutar DS, Gordon MacDonald D, Shoaib T, Camilleri I, Roberton AG, et al. Sentinel node biopsy in head and neck cancer: preliminary results of a multicenter trial. Ann Surg Oncol. 2004;11:690–6.PubMedCrossRef
13.
Zurück zum Zitat Broglie MA, Haile SR, Stoeckli SJ. Long-term experience in sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma. Ann Surg Oncol. 2011;18:2732–8.PubMedCrossRef Broglie MA, Haile SR, Stoeckli SJ. Long-term experience in sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma. Ann Surg Oncol. 2011;18:2732–8.PubMedCrossRef
14.
Zurück zum Zitat Civantos FJ, Zitsch RP, Schuller DE, Agrawal A, Smith RB, Nason R, et al. Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1–T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial. J Clin Oncol. 2010;28:1395–400.PubMedCrossRef Civantos FJ, Zitsch RP, Schuller DE, Agrawal A, Smith RB, Nason R, et al. Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1–T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial. J Clin Oncol. 2010;28:1395–400.PubMedCrossRef
15.
Zurück zum Zitat Rassekh CH, Johnson JT, Myers EN. Accuracy of intraoperative staging of the N0 neck in squamous cell carcinoma. Laryngoscope. 1995;105:1334–6.PubMedCrossRef Rassekh CH, Johnson JT, Myers EN. Accuracy of intraoperative staging of the N0 neck in squamous cell carcinoma. Laryngoscope. 1995;105:1334–6.PubMedCrossRef
16.
Zurück zum Zitat Civantos FJ, Gomez C, Duque C, Pedroso F, Goodwin WJ, Weed DT, et al. Sentinel node biopsy in oral cavity cancer: correlation with PET scan and immunohistochemistry. Head Neck. 2003;25:1–9.PubMedCrossRef Civantos FJ, Gomez C, Duque C, Pedroso F, Goodwin WJ, Weed DT, et al. Sentinel node biopsy in oral cavity cancer: correlation with PET scan and immunohistochemistry. Head Neck. 2003;25:1–9.PubMedCrossRef
17.
Zurück zum Zitat Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13:4807–16.PubMedCrossRef Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13:4807–16.PubMedCrossRef
18.
Zurück zum Zitat Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, et al. Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res. 2009;15:2879–84.PubMedCrossRef Tamaki Y, Akiyama F, Iwase T, Kaneko T, Tsuda H, Sato K, et al. Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res. 2009;15:2879–84.PubMedCrossRef
19.
Zurück zum Zitat Schem C, Maass N, Bauerschlag DO, Carstensen MH, Loning T, Roder C, et al. One-step nucleic acid amplification—a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group. Virchows Arch. 2009;454:203–10.PubMedCrossRef Schem C, Maass N, Bauerschlag DO, Carstensen MH, Loning T, Roder C, et al. One-step nucleic acid amplification—a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group. Virchows Arch. 2009;454:203–10.PubMedCrossRef
20.
Zurück zum Zitat Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer. 2008;122:2562–7.PubMedCrossRef Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer. 2008;122:2562–7.PubMedCrossRef
21.
Zurück zum Zitat Yaguchi Y, Sugasawa H, Tsujimoto H, Takata H, Nakabayashi K, Ichikura T, et al. One-step nucleic acid amplification (OSNA) for the application of sentinel node concept in gastric cancer. Ann Surg Oncol. 2011;18:2289–96.PubMedCrossRef Yaguchi Y, Sugasawa H, Tsujimoto H, Takata H, Nakabayashi K, Ichikura T, et al. One-step nucleic acid amplification (OSNA) for the application of sentinel node concept in gastric cancer. Ann Surg Oncol. 2011;18:2289–96.PubMedCrossRef
22.
Zurück zum Zitat Yamamoto H, Sekimoto M, Oya M, Yamamoto N, Konishi F, Sasaki J, et al. OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan. Ann Surg Oncol. 2011;18:1891–8.PubMedCrossRef Yamamoto H, Sekimoto M, Oya M, Yamamoto N, Konishi F, Sasaki J, et al. OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan. Ann Surg Oncol. 2011;18:1891–8.PubMedCrossRef
23.
Zurück zum Zitat Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000;28:E63.PubMedCrossRef Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000;28:E63.PubMedCrossRef
24.
Zurück zum Zitat Germani RM, Civantos FJ, Elgart G, Roberts B, Franzmann EJ. Molecular markers of micrometastasis in oral cavity carcinomas. Otolaryngol Head Neck Surg. 2009;141:52–8.PubMedCrossRef Germani RM, Civantos FJ, Elgart G, Roberts B, Franzmann EJ. Molecular markers of micrometastasis in oral cavity carcinomas. Otolaryngol Head Neck Surg. 2009;141:52–8.PubMedCrossRef
25.
Zurück zum Zitat Ferris RL, Xi L, Seethala RR, Chan J, Desai S, Hoch B, et al. Intraoperative qRT-PCR for detection of lymph node metastasis in head and neck cancer. Clin Cancer Res. 2011;17:1858–66.PubMedCrossRef Ferris RL, Xi L, Seethala RR, Chan J, Desai S, Hoch B, et al. Intraoperative qRT-PCR for detection of lymph node metastasis in head and neck cancer. Clin Cancer Res. 2011;17:1858–66.PubMedCrossRef
26.
Zurück zum Zitat Tao L, Lefevre M, Ricci S, Saintigny P, Callard P, Perie S, et al. Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT-PCR detection of cytokeratin 19 mRNA. Br J Cancer. 2006;94:1164–9.PubMedCrossRef Tao L, Lefevre M, Ricci S, Saintigny P, Callard P, Perie S, et al. Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT-PCR detection of cytokeratin 19 mRNA. Br J Cancer. 2006;94:1164–9.PubMedCrossRef
27.
Zurück zum Zitat Zhong LP, Zhao SF, Chen GF, Ping FY, Xu ZF, Hu JA. Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction. Arch Oral Biol. 2006;51:1112–9.PubMedCrossRef Zhong LP, Zhao SF, Chen GF, Ping FY, Xu ZF, Hu JA. Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction. Arch Oral Biol. 2006;51:1112–9.PubMedCrossRef
28.
Zurück zum Zitat Xu Y, Zhao X, Guan M, Li B, Zhou Y, Zhou F. Determination of lymph node micrometastases in patients with supraglottic carcinoma. Acta Otolaryngol. 2007;127:1188–95.PubMedCrossRef Xu Y, Zhao X, Guan M, Li B, Zhou Y, Zhou F. Determination of lymph node micrometastases in patients with supraglottic carcinoma. Acta Otolaryngol. 2007;127:1188–95.PubMedCrossRef
29.
Zurück zum Zitat Zhong LP, Chen WT, Zhang CP, Zhang ZY. Increased CK19 expression correlated with pathologic differentiation grade and prognosis in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:377–84.PubMedCrossRef Zhong LP, Chen WT, Zhang CP, Zhang ZY. Increased CK19 expression correlated with pathologic differentiation grade and prognosis in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:377–84.PubMedCrossRef
30.
Zurück zum Zitat Yamauchi K, Fujioka Y, Kogashiwa Y, Kohno N. Quantitative expression study of four cytokeratins and p63 in squamous cell carcinoma of the tongue: suitability for sentinel node navigation surgery using one-step nucleic acid amplification. J Clin Pathol. 2011;64:875–9.PubMedCrossRef Yamauchi K, Fujioka Y, Kogashiwa Y, Kohno N. Quantitative expression study of four cytokeratins and p63 in squamous cell carcinoma of the tongue: suitability for sentinel node navigation surgery using one-step nucleic acid amplification. J Clin Pathol. 2011;64:875–9.PubMedCrossRef
Metadaten
Titel
Intraoperative Molecular Assessment for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma Using One-Step Nucleic Acid Amplification (OSNA) Assay
verfasst von
Takashi Matsuzuka, MD, PhD
Katsumasa Takahashi, MD, PhD
Daisuke Kawakita, MD, PhD
Naoyuki Kohno, MD, PhD
Hiroshi Nagafuji, MD
Koichi Yamauchi, MD, PhD
Masahiro Suzuki, MD
Tomohiro Miura, MD, PhD
Nobuhiko Furuya, MD, PhD
Yasushi Yatabe, MD, PhD
Keitaro Matsuo, MD, PhD, MSc
Koichi Omori, MD, PhD
Yasuhisa Hasegawa, MD, PhD
Publikationsdatum
01.11.2012
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 12/2012
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2409-0

Weitere Artikel der Ausgabe 12/2012

Annals of Surgical Oncology 12/2012 Zur Ausgabe

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Deutlich weniger Infektionen: Wundprotektoren schützen!

08.05.2024 Postoperative Wundinfektion Nachrichten

Der Einsatz von Wundprotektoren bei offenen Eingriffen am unteren Gastrointestinaltrakt schützt vor Infektionen im Op.-Gebiet – und dient darüber hinaus der besseren Sicht. Das bestätigt mit großer Robustheit eine randomisierte Studie im Fachblatt JAMA Surgery.

Chirurginnen und Chirurgen sind stark suizidgefährdet

07.05.2024 Suizid Nachrichten

Der belastende Arbeitsalltag wirkt sich negativ auf die psychische Gesundheit der Angehörigen ärztlicher Berufsgruppen aus. Chirurginnen und Chirurgen bilden da keine Ausnahme, im Gegenteil.

Update Chirurgie

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

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.