Hintergrund: Das Mammakarzinom stellt weltweit die häufigste maligne Tumorerkrankung der Frau dar und wird immer noch größtenteils als primär systemische Krebsform angesehen. Nach Primärbehandlung werden 5-Jahresüberlebensraten von 80% erreicht. Jedoch überleben Patientinnen, bei denen ein Stadium IV vorliegt, im median nur 20-30 Monate. 5-15% dieser Patientinnen weisen dabei einen isolierten metastatischen Befall der Lunge auf, der als Oligometastasierung im Sinne eines stabilen Zwischenstadiums der Erkrankung angesehen werden kann und somit einer lokalen Therapie zugänglich ist. Etliche Studien weisen darauf hin, dass gerade diese Frauen von einer Resektion ihrer Lungenmetastasen deutlich mehr profitieren können, als von medikamentöser systemischer Therapie allein. Zudem kann das Rezeptorverhalten (Östrogen-, Progesteron-, HER2-Rezeptor) zwischen primärem Mammakarzinom und dessen Metastasen differieren, was in bisher noch nicht geklärtem Umfang Änderungen des Behandlungsschemas zur Folge hat. Frage- und Zielstellung: Ziel der vorliegenden Arbeit ist es, das Outcome von Patientinnen mit pulmonal metastasiertem Mammakarzinom, deren Lungenmetastasen ausschließlich mit einer neuen parenchymsparenden 1318-nm-Lasertechnik reseziert wurden, im Verlauf zu untersuchen und unabhängige prognostische Faktoren zu identifizieren. Weiterhin soll der Nachweis einer Rezeptordiskordanz speziell für pulmonale Fernmetastasen erbracht und aufgezeigt werden, in welchen Größenordnungen mit solchen Rezeptorwechseln zu rechnen ist. Patientinnen und Methoden: Im Rahmen dieser retrospektiven Studie wurde vom 01.01.1996 bis 31.12.2012 bei insgesamt 102 Patientinnen im Alter von 33 bis 78 Jahren und einem Durchschnittsalter von 58 Jahren eine kurative pulmonale Laser-Metastasenresektion mit systematischer Lymphadenektomie vorgenommen. Vorgegebene Einschlusskriterien waren die vollständige Resektion und Kontrolle des Primärtumors sowie das Fehlen von extrapulmonalen/-thorakalen Metastasen bzw. deren präoperative erfolgreiche Therapie. Eine Limitierung bezüglich der Zahl der Lungenmetastasen wurde nicht vorgegeben, allerdings mussten die technische Resektabilität und die funktionelle Operabilität aus der präoperativen Diagnostik ableitbar sein. Mit Hilfe der Kaplan-Meier-Methode wurde das Gesamtüberleben des Patientenkollektivs sowie ausgewählter Subgruppen analysiert. Das Cox-Proportional-Hazard-Modell wurde verwendet, um im uni- und multivariaten Verfahren prognostische Faktoren zu ermitteln. Zum Vergleich des Rezeptorstatus von Primärtumor und Metastasen kam der McNemare-Test zum Einsatz. Eine statistische Signifikanz wurde bei p-Werten von < 0,05 angenommen. Ergebnisse: Insgesamt wurden 936 Lungentumore entfernt, von denen sich nach histopathologischer Sicherung 716 als Metastasen des anamnestisch bekannten Mammakarzinoms erwiesen. Die Anzahl reichte von einer solitären Metastase bis zu 61 zweizeitig entfernten Metastasen (durchschnittlich 7 pro Patientin). Die Lobektomierate betrug 0,98% (n=1). In 7,8% (n=8) der Fälle waren zusätzlich lappensparende Laser-Segmentresektionen möglich. R0-Resektionen konnten bei 73,5% (n=75) der Patientinnen erreicht werden. Das mediane Gesamtüberleben betrug 43 Monate, die 5-Jahresüberlebensrate belief sich auf 46,1%. Als unabhängige prognostische Faktoren konnten der Resektionsstatus (p=0,02), der intrathorakale Lymphknotenbefall (p=0,001) und die Expression des Östrogenrezeptors (p=0,018) nachgewiesen werden. Das Risiko zu versterben war bei tumorbefallenen Lymphknoten und bei fehlender Ausprägung des Östrogenrezeptors 3,2- bzw. 2-fach erhöht. Die Anzahl der resezierten Metastasen, die Art des Lungenbefalls (uni-/bilateral), das krankheitsfreie Überleben nach Primär-Operation (</> 36 Monate) und die Expression des Progesteronrezeptors hatten keinen signifikanten Einfluss auf das Überleben. Angaben zum primären und metastatischen Hormonrezeptor- bzw. HER2-Status waren bei 88,2% (n=90) bzw. 62,7% (n=64) der Patientinnen verfügbar. Es fanden sich Diskordanzraten bzgl. des Östrogen-, Progesteron- und HER2-Rezeptors von 26,7%, 41,1% bzw. 28,1%. Eine Signifikanz der Abweichung zwischen Primärtumor und Metastasen konnte lediglich für den Östrogenrezeptor nachgewiesen werden (p=0,002). In einer Nebenbetrachtung der vorliegenden Arbeit konnten bei 157 Mammakarzinom-Patientinnen mit neu aufgetretenen, radiologisch detektierten Lungenrundherden in 65,6% der Fälle Metastasen des Mammakarzinoms histologisch gesichert werden. Bei den übrigen Befunden handelte es sich um andere therapiebedürftige maligne Tumore und zu etwa 20% um benigne Befunde. Schlussfolgerungen: Die vorliegenden Ergebnisse bekräftigen den positiven Einfluss der Lungenmetastasektomie auf das Überleben ausgewählter Mammakarzinom-Patientinnen mit isolierter pulmonaler Oligometastasierung. Dabei können mit der Anwendung der parenchymsparenden 1318 nm -Lasertechnik, auch bei Vorhandensein von multiplen und beidseitigen Lungenmetastasen, in größerem Umfang als bisher berichtet, vollständige Resektionen ohne wesentlichen Funktionsverlust und somit guter Lebensqualität erreicht werden. Ungeachtet höherer Zahlen resezierter pulmonaler Metastasen werden gegenüber konventionellen Operationstechniken, auch beim pulmonal metastasierten Mammakarzinom, vergleichbare Überlebensraten erreicht. Die Anzahl der präoperativ diagnostizierten Lungenmetastasen sollte daher einen geringen Einfluss auf die Indikationsstellung zur Operation haben, weshalb diesbezüglich eine Erweiterung der Einschlusskriterien sinnvoll erscheint. Eine R0-Resektion konnte erneut als wichtigster prognostischer Parameter bestätigt werden und sollte deshalb stets oberstes Ziel des Operateurs sein. Das wesentlich schlechtere Outcome unvollständig operierter Patientinnen sowie der Vergleich mit der Literatur zur alleinigen systemischen Therapie zeigen, dass das analysierte Patientenkollektiv von einer Resektion der pulmonalen Mammakarzinom-Metastasen deutlich mehr profitieren kann, als von medikamentöser Behandlung allein. Ein intrathorakaler Lymphknotenbefall wurde, nach unserem Wissen, erstmals bei Patientinnen mit isolierten Lungenmetastasen eines Mammakarzinoms, trotz radikaler Ausräumung, als signifikante negative Einflussgröße auf das Überleben nachgewiesen. In Anlehnung an die Therapie des Lungenkarzinoms sollte trotz dessen, zumindest bis zum Vorliegen weiterführender Studien, standardmäßig eine intraoperative systematische Lymphadenektomie durchgeführt werden. Bei positivem Tumornachweis ist eine komplette Lymphknotendissektion zu erwägen, um keine Patientin von einer potenziell kurativen Therapie auszuschließen. Den vorliegenden Ergebnissen zufolge, darf des Weiteren speziell bei Verdacht auf pulmonale Mammakarzinom-Metastasen nicht von einer Konstanz der Expression der Steroidhormon- bzw. HER2-Rezeptoren, insbesondere der des Östrogenrezeptors, ausgegangen werden. Änderungen zum primären Befund treten dabei in relevanten Größenordnungen auf. Die Bestimmung eines aktuellen Rezeptorstatus sollte nach Metastasektomie obligat durchgeführt werden. Bezüglich der Frage des Ursprungs pulmonaler Rundherde bei bekanntem Mammakarzinom kann darüber hinaus durch deren Resektion mit nachfolgender histopathologischer Analyse sicher zwischen Metastasen, Lungenkarzinomen und benignen Tumoren differenziert werden. Insgesamt ermöglicht dies konkrete Therapieentscheidungen zu treffen. Um Patientinnen jedoch in zeitlich limitierter oligometastatischer Tumorausbreitung zu diagnostizieren und einer bestmöglichen Therapie, einschließlich der Resektion, zuzuführen, ist zufolge unserer Daten sowie der neueren Literatur eine konsequente, engmaschige und zudem apparative Nachsorge notwendig. Dieser Problematik wird gegenwärtig in den aktuellen Leitlinien nicht adäquat Rechnung getragen, da sich die Autoren auf ältere, heutzutage kritisch zu hinterfragende Analysen beziehen. Als Limitationen der vorgelegten Arbeit sind das retrospektive Studiendesign und die Form der Kohortenanalyse, die uneinheitliche Bestimmung des primären Rezeptorstatus sowie die Heterogenität der postoperativen Anschlusstherapien anzusehen. Zukünftig sind größere, multizentrische und randomisierte Studien notwendig, um weiterführende Daten zu generieren und die pulmonale Lasermetastasektomie beim Mammakarzinom im Rahmen multimodaler Therapien möglicherweise weiter zu etablieren sowie den Wert einer erweiterten Nachsorge zu evaluieren.:1. Einleitung und Zielstellung 1 1.1 Epidemiologie des Mammakarzinoms 1 1.2 Lungenmetastasen beim Mammakarzinom 3 1.3 Bedeutung d. pulmonalen Metastasektomie beim metastasierten Mammakarzinom 6 1.4 Steroidhormon- und HER2-Rezeptorstatus 10 1.5 Problem- und Zielstellung 12 2. Patientinnen und Methoden 14 2.1 Datenerfassung 14 2.2 Patientinnen, Ein- und Ausschlusskriterien 15 2.3 Methoden 17 2.3.1 Operationstechniken 17 2.3.2 Historie, Entwicklung und Grundlagen des Lasers und der Laser- Metastasektomie 20 2.3.3 Histopathologische und immunhistochemische Bestimmung des Hormon- und HER2-Rezeptorstatus 24 2.3.4 Statistische Auswertung 26 3. Ergebnisse 27 3.1 Lungenrundherd bei bekanntem Mammakarzinom 27 3.2 Allgemeine Ergebnisse 29 3.3 Langzeitüberleben 31 3.3.1 Gesamtüberleben 31 3.3.2 Resektionsstatus 34 3.3.3 Krankheitsfreies Überleben 36 3.3.4 Lymphknotenbefall 37 3.3.5 Hormonrezeptorstatus 38 3.3.6 Lungenbefall 40 3.3.7 Anzahl resezierter Metastasen 41 3.4 Mortalitätsrisikoanalyse 42 3.5 Rezeptorstatus 44 3.5.1 Hormonrezeptorstatus 44 3.5.2 Östrogenrezeptor 46 3.5.3 Progesteronrezeptor 47 3.5.4 HER2-neu-Rezeptorstatus 48 4. Diskussion 49 4.1 Lungenrundherd bei bekanntem Mammakarzinom 53 4.2 Lasermetastasektomie 57 4.3 Langzeitüberleben 59 4.3.1 Gesamtüberleben 59 4.3.2 Resektionsstatus 61 4.3.3 Anzahl resezierter Metastasen 63 4.3.4 Einseitiger versus beidseitiger Lungenbefall 66 4.3.5 Lymphknotenbefall 68 4.3.6 Krankheitsfreies Überleben 71 4.4 Mortalitätsrisikoanalyse 73 4.5 Hormon- und HER2-Rezeptorstatus 75 4.5.1 Hormonrezeptorstatus 75 4.5.2 HER2-Rezeptor 80 4.5.3 Einflussfaktoren für Rezeptordiskordanz 82 5. Zusammenfassung/Summary 84 5.1 Deutsch 84 5.2 Englisch 88 Abkürzungsverzeichnis 91 Abbildungsverzeichnis 92 Tabellenverzeichnis 93 Literaturverzeichnis 94 Anhang 108 Danksagung 108 Erklärung zur Eröffnung des Promotionsverfahrens 109 Erklärung über die Einhaltung der gesetzlichen Vorgaben im Rahmen der Dissertation 110 / Background: Breast carcinoma is the most common type of cancer in women worldwide and is still regarded as a systemic disease. After primary treatment five-year survival rates around 80% are reported. However, the mean survival time of stadium-IV classified patients is 20-30 months. 5-15% of patients appear with isolated metastases of the lungs which can be considered as an oligometastatic and, therefore, stable intermediate stage in disease process. Several studies point out that especially these women are more likely to benefit from resection of lung metastases than from systemic therapy alone. Furthermore, there is the possibility of a discordant expression of typical receptors (Estrogen-, Progesterone- and HER2-receptor) between primary breast cancer and its paired metastases. As a result a change in treatment regimen might be necessary. Objective: The aim of the present study was to evaluate long-time survival of patients with lung metastases from breast cancer who have been operated exclusively with a new parenchyma-saving and lobe-sparing 1318-nm-lasertechnique. Additionally, the identification of independent prognostic factors was of interest. Furthermore, existence and magnitude of receptor discordance, specifically for distant pulmonary metastases, should be proved. Patients and methods: Within this retrospective study between 1996 and 2012 102 patients (mean age 58; range 33-78 years) underwent curative laser metastasectomy and systematic lymphadenectomy. Inclusion criteria were complete resection of primary breast cancer and absence of extrapulmonary/-thoracal metastases or its previous total treatment. Although there were no limitations regarding the number of metastases, technical resectability and functional operability had to be assumed after the preoperative diagnostics. Kaplan-Meier-analysis was performed to assess overall survival in all patients and selected subgroups. Uni- and multivariate analyses of prognostic factors were performed using the Cox-proportional-hazard model. Comparison of the receptor status of primary breast cancer and paired lung metastases was assessed by the McNemare method. Significant results were assumed if p-values were <0.05. Results: In total 936 intrapulmonary nodules had been resected, including 716 histopathologically confirmed breast cancer metastases. The amount reached from a single metastasis up to 61 two-staged removed pulmonary nodules (mean 7 per patient). The lobectomy rate was 0.98%. In 7.8% of all cases segment-resections, also performed by laser, were possible. Complete resection was achieved in 73.5% (n=75). The median overall survival time was 43 months and the five-year survival rate was 46.1%. As independent prognostic factors resection status (p=0.02), involvement of intrathoracal lymph nodes (p=0.001) and expression of estrogen receptor (p=0.018) were identified. The mortality rate in case of lymph node involvement and negative estrogen receptor status was increased by 3.2- and 2-fold, respectively. The number of resected metastases, type of lung affection (uni-/bilateral), disease free interval after primary breast surgery (</> 36 months), and expression of progesterone receptor had no significant influence on survival. Data concerning the primary and metastatic hormone receptor- and HER2-status were available in 88.2% (n=90) and 62.7% (n=64) of all cases, respectively. Discordant results appeared in 26.7%, 41.1%, and 28.1% regarding the estrogen-, progesterone- and HER2-receptor. Significance of these findings had only been proved for estrogen receptor (p=0.002). A subanalysis of the present study revealed that 65.5% of 157 breast cancer patients who presented with newly occurred radiologically detectable pulmonary nodules had histopathologically confirmed paired metastases. The remaining results showed malignancies other than known breast cancer, and in approximately 20% of all cases there were benign lesions. Conclusions: The results of the present study emphasize the favorable effect of the lung metastasectomy on survival of selected breast cancer patients with isolated pulmonary oligometastatic disease. Via the use of the parenchyma-saving 1318nm-lasertechnique even in case of distinct and bilateral pulmonary metastatic involvement, increased rates of complete resection without substantial loss of lung function can be achieved. Therefore, an adequate quality of life is provided. In comparison with conventional surgery practices, this procedure creates similar survival rates despite higher numbers of resected lung metastases. That is why the number of preoperatively diagnosed metastases should have little influence on decision upon surgery. Thus, an extension of inclusion criteria seems reasonable. Again, complete resection appeared as one of the most important prognostic parameters and should, therefore, be the main objective of the surgeon. The poorer outcome for women with incomplete resections and the results of studies on systemic therapy implicate once more that breast cancer patients are more likely to benefit from the resection of their pulmonary metastases than from medical treatment alone. Furthermore, for the first time according to our knowledge, despite radical excision intrathoracal lymph node involvement has been proved as a significant negative predictive determinant in a collective of patients with isolated pulmonary metastases of breast cancer. Nevertheless, an intraoperative systematic lymph node sampling should be considered, at least until further studies are presented. In reference to the surgical approach of lung carcinoma, as circumstances require, a complete lymph node dissection should be performed to provide potential curative treatment to those affected. Moreover, according to the present findings, in case of the appearance of lung metastases the constancy of metastatic steroid hormone- and HER2 receptor expression, especially of the estrogen receptor, cannot always be assumed. Changes in comparison to the primary carcinoma appear in a relevant number of cases. Thus, the current metastatic receptor status should be evaluated obligatorily after pulmonary metastasectomy. Regarding the origin of pulmonary nodules of patients with history of breast cancer, their surgical resection with subsequent histopathological analysis can reliably differentiate between metastases, lung carcinoma or benign tumors. Altogether this facilitates specific and accurate treatment decisions. However, to identify patients with a limited and stable oligometastatic state of disease and to introduce optimal treatment, including surgical resection, an early, continuous, and also instrument-based follow-up is necessary. This matter is still only slightly taken into account, while the authors of the current guidelines refer to out of date studies, which have to be seen critically. As limitations of the present investigation, the retrospective study design, inconsistent evaluation of the primary receptor status, and also heterogeneity of postoperative medical therapy must be mentioned. In the future larger, multicentric, prospective, randomized trials are necessary to acquire further data, to conceivably continue to establish the pulmonary laser metastasectomy in multimodal therapy settings and also to determine the value of an extended follow-up.  :1. Einleitung und Zielstellung 1 1.1 Epidemiologie des Mammakarzinoms 1 1.2 Lungenmetastasen beim Mammakarzinom 3 1.3 Bedeutung d. pulmonalen Metastasektomie beim metastasierten Mammakarzinom 6 1.4 Steroidhormon- und HER2-Rezeptorstatus 10 1.5 Problem- und Zielstellung 12 2. Patientinnen und Methoden 14 2.1 Datenerfassung 14 2.2 Patientinnen, Ein- und Ausschlusskriterien 15 2.3 Methoden 17 2.3.1 Operationstechniken 17 2.3.2 Historie, Entwicklung und Grundlagen des Lasers und der Laser- Metastasektomie 20 2.3.3 Histopathologische und immunhistochemische Bestimmung des Hormon- und HER2-Rezeptorstatus 24 2.3.4 Statistische Auswertung 26 3. Ergebnisse 27 3.1 Lungenrundherd bei bekanntem Mammakarzinom 27 3.2 Allgemeine Ergebnisse 29 3.3 Langzeitüberleben 31 3.3.1 Gesamtüberleben 31 3.3.2 Resektionsstatus 34 3.3.3 Krankheitsfreies Überleben 36 3.3.4 Lymphknotenbefall 37 3.3.5 Hormonrezeptorstatus 38 3.3.6 Lungenbefall 40 3.3.7 Anzahl resezierter Metastasen 41 3.4 Mortalitätsrisikoanalyse 42 3.5 Rezeptorstatus 44 3.5.1 Hormonrezeptorstatus 44 3.5.2 Östrogenrezeptor 46 3.5.3 Progesteronrezeptor 47 3.5.4 HER2-neu-Rezeptorstatus 48 4. Diskussion 49 4.1 Lungenrundherd bei bekanntem Mammakarzinom 53 4.2 Lasermetastasektomie 57 4.3 Langzeitüberleben 59 4.3.1 Gesamtüberleben 59 4.3.2 Resektionsstatus 61 4.3.3 Anzahl resezierter Metastasen 63 4.3.4 Einseitiger versus beidseitiger Lungenbefall 66 4.3.5 Lymphknotenbefall 68 4.3.6 Krankheitsfreies Überleben 71 4.4 Mortalitätsrisikoanalyse 73 4.5 Hormon- und HER2-Rezeptorstatus 75 4.5.1 Hormonrezeptorstatus 75 4.5.2 HER2-Rezeptor 80 4.5.3 Einflussfaktoren für Rezeptordiskordanz 82 5. Zusammenfassung/Summary 84 5.1 Deutsch 84 5.2 Englisch 88 Abkürzungsverzeichnis 91 Abbildungsverzeichnis 92 Tabellenverzeichnis 93 Literaturverzeichnis 94 Anhang 108 Danksagung 108 Erklärung zur Eröffnung des Promotionsverfahrens 109 Erklärung über die Einhaltung der gesetzlichen Vorgaben im Rahmen der Dissertation 110

The purpose of this study was to identify central neuronal sites activated by stimulation of cardiac ischemia-sensitive afferent neurons and determine whether electrical stimulation of left vagal afferent fibers modified the pattern of neuronal activation. Fos-like immunoreactivity (Fos-LI) was used as an index of neuronal activation in selected levels of cervical and thoracic spinal cord and brain stem. Adult Sprague-Dawley rats were anesthetized with urethane and underwent intrapericardial infusion of an "inflammatory exudate solution" (IES) containing algogenic substances that are released during ischemia (10 mM adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine) or occlusion of the left anterior descending coronary artery (CoAO) to activate cardiac ischemia-sensitive (nociceptive) afferent fibers. IES and CoAO increased Fos-LI above resting levels in dorsal horns in laminae I-V at C2 and T4 and in the caudal nucleus tractus solitarius. Dorsal rhizotomy virtually eliminated Fos-LI in the spinal cord as well as the brain stem. Neuromodulation of the ischemic signal by electrical stimulation of the central end of the left thoracic vagus excited neurons at the cervical and brain stem level but inhibited neurons at the thoracic spinal cord during IES or CoAO. These results suggest that stimulation of the left thoracic vagus excites descending inhibitory pathways. Inhibition at the thoracic spinal level that suppresses the ischemic (nociceptive) input signal may occur by a short-loop descending pathway via signals from cervical propriospinal circuits and/or a longer-loop descending pathway via signals from the nucleus tractus solitarius.

Background: Effects of cardiovascular (CV) risk factors on the diameter of the thoracic aorta have not been fully studied. This study examined the associations between CV risk factors and diameter of thoracic aorta. Materials and Methods: Study population comprised of 1273 asymptomatic adults aged ≥18 years from Central Appalachia region of the United States who participated in a coronary artery screening between January 2014 and December 2016. Descriptive statistics and multiple linear regression analyses were performed to examine associations between multiple CV risk factors and diameters of the thoracic aorta. Results: Mean (±SD) age of participants was 57.9±9.7 years; that of body mass index (BMI) was 29.4±5.9. The mean aortic sinus, ascending aorta, and descending aorta diameter were 34.1±4.4 mm, 33.8±4.4 mm, and 26.0±3.6 mm, respectively. Increasing age, being male, and having a higher BMI were associated with wider aortic sinus, ascending aorta, and descending aorta diameters. Hypertension (p < 0.05) and obesity (p < 0.0001) were significantly associated with wider diameter for all measured aortic diameters. Participants with diabetes had wider descending aorta compared to those without (26.6±3.9 mm vs. 25.9±3.5 mm, P = 0.012). Participants who had ever smoked a cigarette had significantly wider descending aorta diameter compared to never smokers (26.3±3.6 mm vs. 25.9±3.5 mm, p = 0.031). Conclusions: The study results suggest that decreasing BMI and management of CV risk factors such as hypertension and modifying behavioral risk factors such as smoking are likely to be emphasized in order to decrease the rate of aortic dilatation and subsequent aortic dissection, if aortic dilatation is detected during a CT scan.

Introduction: As the number of minimally invasive technologies increases in the field of thoracic surgery, so have the number of learning curve analyses performed for these innovations. Variation in learning curve methodology makes between-study comparisons and evidence syntheses difficult. Furthermore, poorly described and reported learning curve analyses make the results difficult to apply to different clinical settings. The objective of this systematic review is to characterize the variability in the methods used to construct and describe learning curves, with the goal of identifying shortcomings and potential areas for improvement in this line of research. Methods: A search of Ovid Medline, Ovid Embase, EBSCO CINAHL, and Web of Science was performed. Studies of learning curves of anatomical lung resection operations in adult patients published in the English language were eligible for inclusion. Two reviewers independently assessed studies for eligibility, and extracted relevant data. Results: The search yielded 56 articles eligible for inclusion in the present review. A variety of methods were used to construct the learning curve, with chronological grouping of cases being the most commonly used technique in 22 (39.29%) studies, followed by the cumulative sum method, employed in 21 (37.50%) studies. A total of 15 unique metrics were used for learning curve analyses; operative time was the most common metric, used in 39 (69.64%) studies. A large proportion of studies failed to provide details on learning curve parameters such as competency thresholds, surgeon’s prior experience, case complexity, and learning curve definition. Considerable heterogeneity was found in the methods and reporting standards of learning curve evaluations in minimally invasive thoracic surgery. Conflicts of Interest: None. Funding Source: Boris Family Centre for Robotic Surgery. / Thesis / Master of Science (MSc)

Purpose The purpose of this study was to quantify the number of surgical programs currently training osteopathic residents and to solicit advice for current osteopathic medical students who are interested in pursuing a surgical residency. Methods A questionnaire was sent to all listed Electronic Residency Application Service® (ERAS®) email contacts for the following specialties: General Surgery, Neurological Surgery, Orthopedic Surgery, Otolaryngology, Urology, Integrated Vascular Surgery, Integrated Plastic Surgery, and Integrated Thoracic Surgery. The questionnaire was sent a total of three times. Results Two hundred sixty-four of the 1,040 surgical residency programs responded to the questionnaire. Of these responses, 19% were formerly American Osteopathic Association (AOA) accredited programs. About 47.3% of responding programs indicated they are not currently training an osteopathic physician. One hundred thirteen programs provided additional comments on how osteopathic medical students may improve the competitiveness of their residency applications. These comments included increasing volumes of research activities, performing well on the United States Medical Licensing Exam (USMLE), and completing a sub-internship in the desired field or at a specific institution. Conclusion Osteopathic students still face many barriers to matching into surgical residencies. This study provides concrete steps students may take to increase the competitiveness of their application.

Bien que la spirométrie incitative (SI) face partie intégrante des soins périopératoires, son utilisation et impact chez les patients demeurent incertaines, particulièrement lorsqu’elle est initiée en préopératoire. Dans cette étude clinique randomisée prospective à simple insu, l'objectif primaire était de déterminer si un programme préopératoire d'exercice inspiratoire basé sur la SI avait un impact sur les complications pulmonaires après une chirurgie thoracique. Un total de 141 patients à risque de complications pulmonaires a été analysé, soit 72 dans le groupe SI + soins usuels et 69 dans le groupe soins usuels. L'incidence de complications pulmonaires était de 38,3%. Une diminution significative de l’atélectasie pulmonaire avec impact clinique a été observée chez le groupe SI + soins usuels en comparaison au groupe soins usuels (SI + soins usuels 9,7% vs soins usuels 23,2%, p = 0,031). L'impact semblait bénéficier davantage aux patients ayant eu une VATS ou lobectomie pulmonaire. Dans une analyse multivariée tenant compte des facteurs confondants, le groupe soins usuels développait plus d’atélectasie pulmonaire avec impact clinique que le groupe SI + soins usuels (OR 3,046, IC95% :1,108 - 8,372). L'incidence des autres complications pulmonaires était similaire entre les deux groupes. Le séjour hospitalier était de < 3 jours dans 34,7% du groupe SI + soins usuels et dans 20,3% du groupe soins usuels (p = 0,062). Donc, l'initiation de la spirométrie incitative en préopératoire chez les patients à risque de complications pulmonaires pourrait faire partie des stratégies de prévention utilisées en préhabilitation. / Although incentive spirometry (IS) is an integral part of perioperative care, its impact on pulmonary complications remains unclear, particularly when initiated preoperatively. In this randomized, single-blind prospective clinical study, the primary objective was to determine if a preoperative inspiratory exercise program based on IS had an impact on pulmonary complications after a thoracic surgery. A total of 141 patients at risk of pulmonary complications were analyzed, 72 in the IS + usual care group and 69 in the usual care group. In our study, the incidence of pulmonary complications was 38.3%. A significant decrease in pulmonary atelectasis with clinical impact was observed in the IS + usual care group compared to the usual care group (IS + usual care 9.7% vs usual care 23.2%, p = 0.031). The impact seemed to benefit patients who had a VATS or pulmonary lobectomy. In a multivariable analysis considering confounding factors, the usual care group developed more pulmonary atelectasis with clinical impact than the IS + usual care group (OR 3.046, 95%CI:1.108 - 8.372). The incidence of other pulmonary complications was similar between the two groups. The hospital stay was < 3 days in 34.7% of the IS + usual care group and in 20.3% of the usual care group (p = 0,062). In conclusion, the initiation of IS preoperatively in patients at risk of pulmonary complications could be part of the prevention strategies used in prehabilitation.

No description available.

Frontal motor vehicle collisions (MVCs) resulted in 10,813 fatalities and 937,000 injuries in 2014, which is more than any other type of MVC. In order to mitigate the injuries and fatalities resulting from MVCs, new safety restraint technologies and more biofidelic anthropomorphic test devices (ATDs) have been developed. However, the biofidelity of these new ATDs must be evaluated, and the mechanisms of injury must be understood in order to accurately predict injury. Evaluating the biomechanical response, injury mechanisms, and injury threshold of the thorax are particularly important because the thorax is one of the most frequently injured body regions in MVCs. Furthermore, sustaining a severe thoracic injury in an MVC significantly increases mortality risk. The overall objective of this dissertation was to evaluate the biomechanical responses of human surrogates under various frontal loading conditions. This objective was divided into three sub-objectives: 1) to evaluate the biofidelity of the current frontal impact ATDs, 2) to evaluate the effect of different safety restraints on occupant responses, and 3) to evaluate rib material properties with respect to sex, age, structural response, and loading history. In order to meet sub-objectives 1 and 2, full-scale frontal sled tests were performed on three different human surrogates: the 50th percentile male Hybrid III (HIII) ATD, the 50th percentile male Test Device for Human Occupant Restraint (THOR-M) ATD, and approximately 50th percentile male post-mortem human surrogates (PMHS). All surrogates were tested under three safety restraint conditions: knee bolster (KB), KB and steering wheel airbag (KB/SWAB), and knee bolster airbag and SWAB (KBAB/SWAB). The kinematic, lower extremity, abdominal, thoracic, and neck responses were then compared between surrogates and restraint conditions. In order to assess biofidelity, the ATD responses were compared to the PMHS responses. For both the kinematic and thoracic responses, the HIII and THOR-M had comparable biofideltiy. However, the HIII responses were slightly more biofidelic. The ATDs experienced similar lower extremity kinetics, but very different kinetics at the upper and lower neck due to differences in design. Evaluation of the different restraint conditions showed that the SWAB and KBAB both affected injury risk. The SWAB decreased head injury risk for all surrogates, and increased or decreased thoracic injury risk, depending on the surrogate. The KBAB decreased the risk of femur injury, but increased or decreased tibia injury risk depending on the surrogate and injury metric used to predict risk. In order to meet sub-objective 3, the tensile material properties of human rib cortical bone and the structural properties of whole ribs were quantified at strain rates similar to those observed in frontal impacts. The rib cortical bone underwent coupon tension testing, while the whole ribs underwent bending tests intended to simulate loading from a frontal impact. The rib material properties accounted for less than 50% of the variation observed in the whole rib structural properties, indicating that other factors, such as rib geometry, were also influencing the structural response of whole ribs. Age was significantly negatively correlated with the modulus, yield stress, failure strain, failure stress, plastic strain energy density, and total strain energy density. However, sex did not significantly influence any of the material properties. Cortical bone material properties were quantified from the ribs that underwent the whole rib bending tests and subject-matched, untested (control) ribs in order to evaluate the effect of loading history on material properties. Yield stress and yield strain were the only material properties that were significantly different between the previously tested and control ribs. The results of this dissertation can guide ATD and safety restrain design. Additionally, this dissertation provides human surrogate response data and rib material property data for the validation of finite element models, which can then be used to evaluate injury mitigation strategies for MVCs. / PHD

Unintentional injuries present a major threat to the health and welfare of humans. Over 120,000 deaths and over 30,000,000 non-fatal injuries are estimated annually in the United States. The leading causes of nonfatal injuries vary with age, but falls, motor vehicle collisions (occupants), and being struck by or against are among the top 4 leading causes of unintentional injury for all ages. The loading mechanism that cause forces to be transmitted to the body during these events can cause a wide assortment of injury types with a range of severities. Understanding the biomechanical response to loading in these environments can facilitate efforts in injury mitigation. Biomechanical responses can be quantified by performing controlled laboratory experiments with human volunteers and surrogates, such as anthropomorphic test devices (ATDs) and post mortem human surrogates (PMHSs). The overall objective of this dissertation is to quantify the biomechanical response to loading regimes present in motor vehicle collisions, falls, and when being struck by or against an object using human volunteers and surrogates. Specifically, the research will achieve the following: quantify the dynamic responses of human volunteers, Hybrid III ATD, and PMHSs in low-speed frontal sled tests; quantify the neck response of human volunteers and PMHSs in low-speed frontal sled tests; quantify the kinetic and kinematic responses of PMHSs and the Hybrid III ATD in high-speed frontal sled tests; characterize thoracic loading as a result of same level falls using a Hybrid III ATD; and quantify the ability of children to swing sword-like toys and the human kinematic response that could be anticipated as a result of forceful impact using a Hybrid III 6-year old head and neck. / Ph. D.

Thesis (MScPhysio)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Introduction-Groin injuries are among the top six most cited injuries in soccer and account for 10-18 per cent of all injuries reported in contact sport. Groin pain can result from a variety of pathologies, but according to literature, 63 per cent of groin pain is due to adductor pathology. Objective-The objective of this study was to explore if there are kinematic differences in the hip joint in sports participants with groin pain compared to matched healthy controls. Study design A cross sectional, descriptive study was conducted. Study setting-The study was conducted at the FNB -3D motion analysis laboratory at the University of Stellenbosch, South Africa. Outcome variables-The dependent variables included hip kinematics in the sagittal, frontal and transverse planes at foot strike, lowest vertical point of the pelvis and total range of hip motion during a single leg drop landing. Methodology-The study sample comprised 20 male club level soccer-and, rugby players, running and cycling participants between the ages of 18-55 years of age. Ten of the subjects had chronic groin pain and the other ten were healthy matched controls. An eight-camera Vicon system was used to analyse the kinematics of the hip joint during single leg drop landing. For the purpose of comparison, the data was analysed for participants with unilateral groin pain and matched controls (n=14) and participants with bilateral groin pain and controls (n=6). The full set of data was subdivided for analysis into three distinct sub-groups. Unilaterally injured groin cases (n=7) were matched with seven healthy controls for analysis. Bilaterally injured groin cases (n=3) were matched with three healthy controls. Results-Cases with unilateral groin pain at initial contact had significantly more abduction of the hip joint when compared to controls (p<0.05). The effect size of this difference was large (0.94). Cases with unilateral groin pain also demonstrated greater hip internal rotation while the controls had external rotation (p<0.05) during a drop landing activity. Bilaterally injured groin cases landed with significantly (p=?) greater ranges of hip flexion as well as in significantly (p=?) more hip abduction during a drop landing activity. They also demonstrated greater total range of motion in the frontal plan when compared to controls. Groin pain cases overall demonstrated greater ranges of motion and tended to land in more abduction compared to controls. Conclusion-This study found that during a single leg drop landing, sports participants with unilateral chronic groin pain landed with significantly greater hip abduction and exhibited larger total range of motion in the transverse plane, which may indicate impaired stability of the hip complex when compared to controls. / AFRIKAANSE OPSOMMING: Inleiding-Liesbeserings is een van die top ses mees prominente sokker beserings. Dit beloop 10-18 persent van alle beserings wat in kontaksport aangemeld word. Liespyn kan die gevolg wees van ‘n verskeidenheid patologië, maar volgens die literatuur is 63 persent van liespyn as gevolg adduktor patologie. Doelwitte-Die doelwit van hierdie studie was om ondersoek in te stel of daar enige kinematiese veranderinge in die heupgewrig is in spelers met liespyn in vergelyking met dieselfde vergelykbare spelers sonder liespyn. Studie Ontwerp-‘n Deursnit, beskrywende studie was onderneem. Studie Omgewing-Die studie was uitgevoer by die FNB-3D bewegingsanalise laboratorium van die Stellenbosch Universiteit, Suid-Afrika. Uitkomsveranderlikes-Die afhanklike veranderlikes het in gesluit die heup kinematika in die sagitale, frontale en transvers vlakke met voet kontak endie laagste vertikale punt van die pelvis sowel as die totale heup omvang van beweging gedurende een been landing. Metodologie-Die studie populasie het bestaan uit 20 manlike sokker- en, rugbyspelers, hardlopers en fietsryers tussen die ouderdomme van 18 en 55 jaar. Tien van die deelnemers het kroniese liespyn gehad en die ander tien in die gelyke gesonde groep was sonder liespyn. Die agt kamera Vicon sisteem was gebruik om die kinematika van die heupgewrig te analseer tydens een been landing. Vir die doel om ‘n vergelyking te kan maak, was die data geanaliseer van deelnemers met unilaterale liespyn en die vergelykende groep sonder liespyn (n=14) en deelnemers met bilaterale liespyn en hulle vergelykende groep sonder liespyn (n=6).. Die volledige stel data was onderverdeel in drie afsonderlike sub groepe. Vir die analiese was unilaterale liesbeserings (n=7) vergelyk met sewe deelnemers sonder liespyn in die kontrolegroep. Deelnemers met bilaterale liesbeserings (n=3) was vergelyk met drie in die kontrolegroep. Resultate-Die deelnemers met unilaterale liespyn het met eerste kontak beduidend meer abduksie van die heupgewrig gehad in vergelyking met die kontrolegroep (p<0.05). Die effek van hierdie verskil was groot (0.94). Die deelnemers met unilaterale liespyn het ook ‘n grooter interne rotasie getoon, terwyl die kontrole groep meer eksterne rotasie gedemonstreer het (p<0.05) met landing. Deelnemers met bilaterale liespyn het beduidend (p=?) meer heup fleksie en abduksie omvang van beweging tydens landing. Hulle het ook ‘n groter totale heup omvang van beweging in die frontale vlak gehad in vergelyking met die kontrolegroep. Deelnemers met liespyn het oor die algemeen ‘n grooter omvang van beweging getoon, en was geneig om met meer abduksie van die heup te land as die kontrolegroep. Gevolgtrekking-Die studie toon dat deelnemers met kroniese unilaterale liespyn, tydens een been landing, beduidende meerheup abduksie toon en dat die heup in die transverse vlak meer totale omvang van beweging gebruik wat kan dui op onstabiliteit in die heupkompleks in vergelyking met die kontrolegroep.