Skip to main content
Erschienen in: Obesity Surgery 1/2017

29.05.2016 | Original Contributions

Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones

verfasst von: Shiying Li, Jiande D. Z. Chen

Erschienen in: Obesity Surgery | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The goals of this experiment were to study therapeutic potential of intestinal electrical stimulation (IES) for obesity, its mechanisms involving gastrointestinal motility and hormones, and role of pulse width in diet-induced obese rats.

Methods

In a 4-week study, rats equipped with one pair of electrodes at the duodenum were assigned to receive either a sham or IES of varied pulse widths in a sequential way. Food intake was measured daily and body weight measured weekly. Blood samples were collected for the measurement of glucagon-like peptide-1 (GLP-1). Solid gastric emptying (GE) and small bowel transit (SIT) tests were performed at the end of the experiment.

Results

The results of the study were as follows: (1) Daily food intake, not affected by IES of 0.3 ms, was pulse width-dependently reduced by 1.9 g with 1 ms and by 5.7 g with 3 ms. Accordingly, body weight was pulse width-dependently reduced by 2.4 g with 1 ms and by 12.8 g with 3 ms compared to a gain of 5.6 g in sham. (2) GLP-1 level was elevated by both 0.3 and 3 ms at 15 min, but was elevated only with 3 ms at 60 min. (3) GE was delayed to 52.3 % by IES of 3 ms but not 0.3 ms, compared to that at 64.4 % with sham IES. (4) Compared to the geometric center of 7.0 with sham IES, SIT was accelerated by 3 ms to 7.8 but not by 0.3 ms.

Conclusion

IES pulse width-dependently reduces food intake and body weight, attributed to the delay of gastric emptying and the acceleration of small bowel transit, as well as the enhancement of GLP-1 secretion.
Literatur
1.
Zurück zum Zitat Hurt RT, Kulisek C, Buchanan LA, et al. The obesity epidemic: challenges, health initiatives, and implications for gastroenterologists. Gastroenterol Hepatol. 2010;6:780–92. Hurt RT, Kulisek C, Buchanan LA, et al. The obesity epidemic: challenges, health initiatives, and implications for gastroenterologists. Gastroenterol Hepatol. 2010;6:780–92.
4.
Zurück zum Zitat Favretti F, De Luca M, Segato G, et al. Treatment of morbid obesity with the transcend implantable gastric stimulator (IGS): a prospective survey. Obes Surg. 2004;14:666–70.CrossRefPubMed Favretti F, De Luca M, Segato G, et al. Treatment of morbid obesity with the transcend implantable gastric stimulator (IGS): a prospective survey. Obes Surg. 2004;14:666–70.CrossRefPubMed
5.
Zurück zum Zitat Greenstein RJ, Belachew M. Implantable gastric stimulation (IGS) as therapy for human morbid obesity: report from the 2001 IFSO symposium in Crete. Obes Surg. 2002;12 Suppl 1:3S–5.CrossRefPubMed Greenstein RJ, Belachew M. Implantable gastric stimulation (IGS) as therapy for human morbid obesity: report from the 2001 IFSO symposium in Crete. Obes Surg. 2002;12 Suppl 1:3S–5.CrossRefPubMed
6.
Zurück zum Zitat Cigaina V. Gastric pacing as therapy for morbid obesity: preliminary results. Obes Surg. 2002;12 Suppl 1:12S–6.CrossRefPubMed Cigaina V. Gastric pacing as therapy for morbid obesity: preliminary results. Obes Surg. 2002;12 Suppl 1:12S–6.CrossRefPubMed
7.
Zurück zum Zitat D’Argent J. Gastric electrical stimulation as therapy of morbid obesity: preliminary results from the French study. Obes Surg. 2002;12 Suppl 1:21S–5.CrossRefPubMed D’Argent J. Gastric electrical stimulation as therapy of morbid obesity: preliminary results from the French study. Obes Surg. 2002;12 Suppl 1:21S–5.CrossRefPubMed
8.
Zurück zum Zitat Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: results of the SHAPE trial. Surg Obes Relat Dis. 2009;5:31–7.CrossRefPubMed Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: results of the SHAPE trial. Surg Obes Relat Dis. 2009;5:31–7.CrossRefPubMed
9.
Zurück zum Zitat Zhang J, Tang M, Chen JD. Gastric electrical stimulation for obesity: the need for a new device using wider pulses. Obesity. 2009;17:474–80.CrossRefPubMed Zhang J, Tang M, Chen JD. Gastric electrical stimulation for obesity: the need for a new device using wider pulses. Obesity. 2009;17:474–80.CrossRefPubMed
10.
Zurück zum Zitat Zhang J, Maude-Griffin R, Zhu H, et al. Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats. Am J Physiol Gastrointest Liver Physiol. 2011;301:G912–8.CrossRefPubMed Zhang J, Maude-Griffin R, Zhu H, et al. Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats. Am J Physiol Gastrointest Liver Physiol. 2011;301:G912–8.CrossRefPubMed
11.
12.
Zurück zum Zitat Yin J, Ouyang H, Chen JD. Potential of intestinal electrical stimulation for obesity: a preliminary canine study. Obesity. 2007;15:1133–8.CrossRefPubMed Yin J, Ouyang H, Chen JD. Potential of intestinal electrical stimulation for obesity: a preliminary canine study. Obesity. 2007;15:1133–8.CrossRefPubMed
13.
Zurück zum Zitat Yin J, Zhang J, Chen JD. Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol. 2007;293:R78–82.CrossRefPubMed Yin J, Zhang J, Chen JD. Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol. 2007;293:R78–82.CrossRefPubMed
14.
Zurück zum Zitat Aberle J, Busch P, Veigel J, et al. Duodenal electric stimulation : results of a first-in-man study. Obes Surg. 2016;26:369–75.CrossRefPubMed Aberle J, Busch P, Veigel J, et al. Duodenal electric stimulation : results of a first-in-man study. Obes Surg. 2016;26:369–75.CrossRefPubMed
15.
Zurück zum Zitat Farley C, Cook JA, Spar BD, et al. Meal pattern analysis of diet-induced obesity in susceptible and resistant rats. Obes Res. 2003;11:845–51.CrossRefPubMed Farley C, Cook JA, Spar BD, et al. Meal pattern analysis of diet-induced obesity in susceptible and resistant rats. Obes Res. 2003;11:845–51.CrossRefPubMed
16.
Zurück zum Zitat Li S, Maude-Griffin R, Pullan AJ, et al. Gastric emptying and Ca(2+) and K(+) channels of circular smooth muscle cells in diet-induced obese prone and resistant rats. Obesity. 2013;21:326–35.CrossRefPubMed Li S, Maude-Griffin R, Pullan AJ, et al. Gastric emptying and Ca(2+) and K(+) channels of circular smooth muscle cells in diet-induced obese prone and resistant rats. Obesity. 2013;21:326–35.CrossRefPubMed
17.
Zurück zum Zitat Sallam HS, Oliveira HM, Gan HT, et al. Ghrelin improves burn-induced delayed gastrointestinal transit in rats. Am J Physiol Regul Integr Comp Physiol. 2007;292:R253–7.CrossRefPubMed Sallam HS, Oliveira HM, Gan HT, et al. Ghrelin improves burn-induced delayed gastrointestinal transit in rats. Am J Physiol Regul Integr Comp Physiol. 2007;292:R253–7.CrossRefPubMed
18.
Zurück zum Zitat Yin J, Chen JD. Mechanisms and potential applications of intestinal electrical stimulation. Dig Dis Sci. 2010;55:1208–20.CrossRefPubMed Yin J, Chen JD. Mechanisms and potential applications of intestinal electrical stimulation. Dig Dis Sci. 2010;55:1208–20.CrossRefPubMed
19.
Zurück zum Zitat Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. 2003;125:421–8.CrossRefPubMed Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. 2003;125:421–8.CrossRefPubMed
20.
Zurück zum Zitat Chen JD, Qian L, Ouyang H, et al. Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs. Gastroenterology. 2003;124:401–9.CrossRefPubMed Chen JD, Qian L, Ouyang H, et al. Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs. Gastroenterology. 2003;124:401–9.CrossRefPubMed
21.
Zurück zum Zitat Du P, Li S, O’Grady G, et al. Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach. Am J Physiol Gastrointest Liver Physiol. 2009;297:G672–80.CrossRefPubMedPubMedCentral Du P, Li S, O’Grady G, et al. Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach. Am J Physiol Gastrointest Liver Physiol. 2009;297:G672–80.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Chen JD, Lin HC. Electrical pacing accelerates intestinal transit slowed by fat-induced ileal brake. Dig Dis Sci. 2003;48:251–6.CrossRefPubMed Chen JD, Lin HC. Electrical pacing accelerates intestinal transit slowed by fat-induced ileal brake. Dig Dis Sci. 2003;48:251–6.CrossRefPubMed
23.
Zurück zum Zitat Zhang J, Chen JD. Pacing the gut in motility disorders. Curr Treat Options Gastroenterol. 2006;9:351–60.CrossRefPubMed Zhang J, Chen JD. Pacing the gut in motility disorders. Curr Treat Options Gastroenterol. 2006;9:351–60.CrossRefPubMed
24.
Zurück zum Zitat Ouyang X, Li S, Foreman R, et al. Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats. Neurogastroenterol Motil. 2015;27:406–15.CrossRefPubMed Ouyang X, Li S, Foreman R, et al. Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats. Neurogastroenterol Motil. 2015;27:406–15.CrossRefPubMed
25.
Zurück zum Zitat Li S, Chen JD. Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1580–7.CrossRefPubMed Li S, Chen JD. Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1580–7.CrossRefPubMed
26.
Zurück zum Zitat Xu J, McNearney TA, Chen JD. Gastric/intestinal electrical stimulation modulates appetite regulatory peptide hormones in the stomach and duodenum in rats. Obes Surg. 2007;17:406–13.CrossRefPubMed Xu J, McNearney TA, Chen JD. Gastric/intestinal electrical stimulation modulates appetite regulatory peptide hormones in the stomach and duodenum in rats. Obes Surg. 2007;17:406–13.CrossRefPubMed
28.
Zurück zum Zitat Naslund E, Gutniak M, Skogar S, et al. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr. 1998;68:525–30.PubMed Naslund E, Gutniak M, Skogar S, et al. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr. 1998;68:525–30.PubMed
29.
Zurück zum Zitat Sun Y, Qin C, Foreman RD, et al. Intestinal electric stimulation modulates neuronal activity in the nucleus of the solitary tract in rats. Neurosci Lett. 2005;385:64–9.CrossRefPubMed Sun Y, Qin C, Foreman RD, et al. Intestinal electric stimulation modulates neuronal activity in the nucleus of the solitary tract in rats. Neurosci Lett. 2005;385:64–9.CrossRefPubMed
30.
Zurück zum Zitat Zhang J, Zhu H, Chen JD. Central neuronal mechanisms of intestinal electrical stimulation: effects on duodenum distention-responsive (DD-R) neurons in the VMH of rats. Neurosci Lett. 2009;457:27–31.CrossRefPubMedPubMedCentral Zhang J, Zhu H, Chen JD. Central neuronal mechanisms of intestinal electrical stimulation: effects on duodenum distention-responsive (DD-R) neurons in the VMH of rats. Neurosci Lett. 2009;457:27–31.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology. 1999;140:1687–94.PubMed Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology. 1999;140:1687–94.PubMed
32.
Zurück zum Zitat Schwartz A, Ort T, Kajekar R, et al. Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release. Physiol Meas. 2010;31:1147–59.CrossRefPubMed Schwartz A, Ort T, Kajekar R, et al. Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release. Physiol Meas. 2010;31:1147–59.CrossRefPubMed
33.
Zurück zum Zitat Sandoval D, Dunki-Jacobs A, Sorrell J, et al. Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo. Neurogastroenterol Motil. 2013;25:700–5.CrossRefPubMedPubMedCentral Sandoval D, Dunki-Jacobs A, Sorrell J, et al. Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo. Neurogastroenterol Motil. 2013;25:700–5.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Cranley B, Kelly KA, Go VL, et al. Enhancing the anti-dumping effect of Roux gastrojejunostomy with intestinal pacing. Ann Surg. 1983;198:516–24.CrossRefPubMedPubMedCentral Cranley B, Kelly KA, Go VL, et al. Enhancing the anti-dumping effect of Roux gastrojejunostomy with intestinal pacing. Ann Surg. 1983;198:516–24.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Layzell T, Collin J. Retrograde electrical pacing of the small intestine—a new treatment for the short bowel syndrome? Br J Surg. 1981;68:711–3.CrossRefPubMed Layzell T, Collin J. Retrograde electrical pacing of the small intestine—a new treatment for the short bowel syndrome? Br J Surg. 1981;68:711–3.CrossRefPubMed
36.
Zurück zum Zitat Miedema BW, Kelly KA. The Roux stasis syndrome. Treatment by pacing and prevention by use of an ‘uncut’ Roux limb. Arch Surg. 1992;127:295–300.CrossRefPubMed Miedema BW, Kelly KA. The Roux stasis syndrome. Treatment by pacing and prevention by use of an ‘uncut’ Roux limb. Arch Surg. 1992;127:295–300.CrossRefPubMed
37.
Zurück zum Zitat Reiser SB, Schusdziarra V, Bollschweiler E, et al. Effect of enteric pacing on intestinal motility and hormone secretion in dogs with short bowel. Gastroenterology. 1991;101:100–6.CrossRefPubMed Reiser SB, Schusdziarra V, Bollschweiler E, et al. Effect of enteric pacing on intestinal motility and hormone secretion in dogs with short bowel. Gastroenterology. 1991;101:100–6.CrossRefPubMed
38.
Zurück zum Zitat Wang WF, Yin JY, De Dz Chen J. Acceleration of small bowel transit in a canine hypermotility model with intestinal electrical stimulation. J Dig Dis. 2015;16:135–42.CrossRefPubMed Wang WF, Yin JY, De Dz Chen J. Acceleration of small bowel transit in a canine hypermotility model with intestinal electrical stimulation. J Dig Dis. 2015;16:135–42.CrossRefPubMed
39.
Zurück zum Zitat Xu X, Lei Y, Chen JD. Duodenum electrical stimulation delays gastric emptying, reduces food intake and accelerates small bowel transit in pigs. Obesity. 2011;19:442–8.CrossRefPubMed Xu X, Lei Y, Chen JD. Duodenum electrical stimulation delays gastric emptying, reduces food intake and accelerates small bowel transit in pigs. Obesity. 2011;19:442–8.CrossRefPubMed
40.
Zurück zum Zitat Lin X, Peters LJ, Hayes J, et al. Entrainment of segmental small intestinal slow waves with electrical stimulation in dogs. Dig Dis Sci. 2000;45:652–6.CrossRefPubMed Lin X, Peters LJ, Hayes J, et al. Entrainment of segmental small intestinal slow waves with electrical stimulation in dogs. Dig Dis Sci. 2000;45:652–6.CrossRefPubMed
41.
Zurück zum Zitat Bjorck S, Kelly KA, Phillips SF. Mechanisms of enhanced canine enteric absorption with intestinal pacing. Am J Physiol. 1987;252:G548–53.PubMed Bjorck S, Kelly KA, Phillips SF. Mechanisms of enhanced canine enteric absorption with intestinal pacing. Am J Physiol. 1987;252:G548–53.PubMed
42.
Zurück zum Zitat Collin J, Kelly KA, Phillips SF. Absorption from the jejunum is increased by forward and backward pacing. Br J Surg. 1979;66:489–92.CrossRefPubMed Collin J, Kelly KA, Phillips SF. Absorption from the jejunum is increased by forward and backward pacing. Br J Surg. 1979;66:489–92.CrossRefPubMed
43.
Zurück zum Zitat Sun Y, Chen JD. Intestinal electric stimulation accelerates whole gut transit and promotes fat excrement in conscious rats. Int J Obes. 2009;33:817–23.CrossRef Sun Y, Chen JD. Intestinal electric stimulation accelerates whole gut transit and promotes fat excrement in conscious rats. Int J Obes. 2009;33:817–23.CrossRef
44.
Zurück zum Zitat Tosetti C, Corinaldesi R, Stanghellini V, et al. Gastric emptying of solids in morbid obesity. Int J Obes Relat Metab Disord. 1996;20:200–5.PubMed Tosetti C, Corinaldesi R, Stanghellini V, et al. Gastric emptying of solids in morbid obesity. Int J Obes Relat Metab Disord. 1996;20:200–5.PubMed
45.
Zurück zum Zitat Wright RA, Krinsky S, Fleeman C, et al. Gastric emptying and obesity. Gastroenterology. 1983;84:747–51.PubMed Wright RA, Krinsky S, Fleeman C, et al. Gastric emptying and obesity. Gastroenterology. 1983;84:747–51.PubMed
46.
Zurück zum Zitat Zahorska-Markiewicz B, Jonderko K, Lelek A, et al. Gastric emptying in obesity. Hum Nutr Clin Nutr. 1986;40:309–13.PubMed Zahorska-Markiewicz B, Jonderko K, Lelek A, et al. Gastric emptying in obesity. Hum Nutr Clin Nutr. 1986;40:309–13.PubMed
47.
Zurück zum Zitat Zhang J, Sha W, Zhu H, et al. Blunted peripheral and central responses to gastric mechanical and electrical stimulations in diet-induced obese rats. J Neurogastroenterol Motil. 2013;19:454–66.CrossRefPubMedPubMedCentral Zhang J, Sha W, Zhu H, et al. Blunted peripheral and central responses to gastric mechanical and electrical stimulations in diet-induced obese rats. J Neurogastroenterol Motil. 2013;19:454–66.CrossRefPubMedPubMedCentral
48.
Zurück zum Zitat Ouyang H, Yin J, Chen JD. Gastric or intestinal electrical stimulation-induced increase in gastric volume is correlated with reduced food intake. Scand J Gastroenterol. 2006;41:1261–6.CrossRefPubMed Ouyang H, Yin J, Chen JD. Gastric or intestinal electrical stimulation-induced increase in gastric volume is correlated with reduced food intake. Scand J Gastroenterol. 2006;41:1261–6.CrossRefPubMed
49.
Zurück zum Zitat Zhao X, Yin J, Chen J, et al. Inhibitory effects and mechanisms of intestinal electrical stimulation on gastric tone, antral contractions, pyloric tone, and gastric emptying in dogs. Am J Physiol Regul Integr Comp Physiol. 2009;296:R36–42.CrossRefPubMed Zhao X, Yin J, Chen J, et al. Inhibitory effects and mechanisms of intestinal electrical stimulation on gastric tone, antral contractions, pyloric tone, and gastric emptying in dogs. Am J Physiol Regul Integr Comp Physiol. 2009;296:R36–42.CrossRefPubMed
Metadaten
Titel
Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones
verfasst von
Shiying Li
Jiande D. Z. Chen
Publikationsdatum
29.05.2016
Verlag
Springer US
Erschienen in
Obesity Surgery / Ausgabe 1/2017
Print ISSN: 0960-8923
Elektronische ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-016-2238-5

Weitere Artikel der Ausgabe 1/2017

Obesity Surgery 1/2017 Zur Ausgabe

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.