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  • Article: Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer.
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    ABSTRACT: PURPOSE: Tumour-associated macrophages have been shown to promote proliferation, angiogenesis and metastasis in several carcinomas. The effect on colon cancer has not yet been clarified. Furthermore, Kupffer cells in the liver might initiate the formation of metastases by directly binding tumour cells. METHODS: An orthotopic syngeneic mouse model of colon cancer as well as a liver metastases model has been studied, using murine CT-26 colon cancer cells in Balb/c-mice. Macrophages were depleted in both models by clodronate liposomes. Tumour sizes and metastases were determined using 7-Tesla MRI. The macrophage and vascular density in the orthotopic tumours as well as the Kupffer cell density in the livers were evaluated using immunohistochemistry. RESULTS: Animals in the macrophage-depleted group displayed significantly smaller primary tumours (37 ± 20 mm(3)) compared to the control group (683 ± 389 mm(3), p = 0.0072). None of the mice in the depleted group showed liver or peritoneal metastases, whereas four of six control mice displayed liver and five out of six mice peritoneal metastases. The vascular density was significantly lower in the macrophage-depleted group (p = 0.0043). In the liver metastases model, animals of the Kupffer cell-depleted group (14.3 ± 7.7) showed significantly less liver metastases than mice of the two control groups (PBS liposomes, 118.5 ± 28.2, p = 0.0117; NaCl, 81.7 ± 23.2, p = 0.0266). The number of liver metastases correlated directly with the Kupffer cell density (p = 0.0221). CONCLUSION: Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.
    International Journal of Colorectal Disease 05/2013; · 2.38 Impact Factor
  • Article: Kritische odontogene Infektion mit Mediastinalbeteiligung
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    ABSTRACT: HintergrundIn seltenen Fllen knnen anfnglich banale odontogene Infektionen auf dem Wege der schrankenlosen Ausbreitung zu vital bedrohlichen Komplikationen fhren. Diese Tatsache hat mit der Einfhrung der Antibiotika, den heute verbesserten Mundhygienetechniken sowie der optimierten Diagnostik und der sich daraus ergebenden Therapie an Bedeutsamkeit verloren. Lebensbedrohliche Komplikationen sind aber weiterhin mglich, insbesondere wenn die Infektion sich entlang der Halsgefscheiden in das obere Mediastinum ausbreitet. Kritische Infektionen haben in anderen Fachdisziplinen in den letzten Jahren allgemein wieder zugenommen. Dies wird durch die Entstehung multiresistenter Infektionserreger insbesondere im Zusammenhang mit nosokomial erworbenen Infektionen begrndet. Wir untersuchten unser Patientengut der letzten 15Jahre dahin gehend, ob auch bei odontogenen Infektionen mit lebensbedrohlichen Komplikationen eine Zunahme zu erkennen ist.Patienten und MethodenIm Zeitraum von 1990–2004 sind in der Klinik fr Mund-, Kiefer- und Gesichtschirurgie der Universitt Kiel vier Patienten mit kritischer phlegmonser Ausbreitung einer odontogenen Infektion intensivmedizinisch behandelt worden. Von diesen Patienten hatten zwei eine nicht operationsbedrftige Mediastinitis, die konservativ mit Antibiose behandelt werden konnte. Ein Patient verstarb an einer Mediastinitis im Rahmen eines generalisierten Herz-Kreislauf-Versagens. Bei einem weiteren Patienten wurde eine Thorakotomie notwendig. Diesen Patienten stellen wir exemplarisch als Fallbericht vor.SchlussfolgerungEntscheidend fr das berleben des Patienten mit einer Mediastinitis sind die frhzeitige Diagnostik mit Computertomographie von Hals und Thorax, die radikale chirurgische Intervention und eine optimale antibiotische Therapie.BackgroundOccasionally, trivial odontogenic infections may develop into complex diseases. This may even result in an unrestrained phlegmonous spread causing life-threatening complications. These problems have decreased since the introduction of antibiotics and also due to improved oral hygiene and improved diagnostic measures resulting in optimized medical treatment. However, life-threatening forms are still seen, in particular if infections spread along the cervical fascial sheaths down towards to the mediastinum. Over the past decade the number of critical infections has increased in other medical specialties. This is usually explained by the development of multiresistant pathogens in the context of nosocomial infections.Patients and methodsWe reviewed the patients records of the past 15years at the Department of Oral and Maxillofacial Surgery of the University Hospital Kiel to assess a possible increase of odontogenic infections with life-threatening complications. From 1990 to 2004, four patientswith odontogenic infections exhibiting critical phlegmonous spread were treated in the intensive care unit. Two patients developed bacterial mediastinitis which could be controlled by intravenous antibiotics only. One patient progressed to general septic mediastinitis and eventually died of cardiorespiratory arrest. The last patient also had septic mediastinitis and developed right pleural empyema. Several operations were necessary before the disease could be controlled. This patients case report is presented in detail.ConclusionThe prognosis of patients with mediastinitis crucially depends on (a) early diagnosis including computed tomography of the neck and thorax, (b) early radical surgical intervention, and (c) optimized pathogen-oriented antibiotic treatment.
    Mund- Kiefer- und Gesichtschirurgie 04/2012; 9(4):257-262.
  • Article: [Disease-Adapted Closure of the Appendicular Stump in Laparoscopic Appendectomy.]
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    ABSTRACT: The frequency of laparoscopic appendectomy has dramatically increased with it now being the standard procedure for acute appendicitis in many hospitals in Germany. Hence, these hospitals require the personnel, the technique as well as the expertise to guarantee a top standard and quality of appendectomies at all times. Only this will meet the requirements of the high case load and the socio-economical importance of appendectomies. The closure of the appendicular stump is a critical step of this procedure. The three most commonly used techniques consist of the endo-loop, the clip and the endo-stapler. The endo-stapler has the advantage of offering closure and transection of the appendix in one step; it can be employed in all cases of appendicular inflammation; and it allows a partial caecal resection. However, it is quite expensive. The clip and the endo-loop offer the same cost-effectiveness, yet the clip appears to be simpler in use compared to the loop. Also, sharing this feature with the stapler, it offers the possibility of closing and transecting the appendix before dissecting the mesoappendix. A disadvantage of the clip not being shared with the loop is the limitation of clips to appendicular diameters of only up to 16 mm. In summary, we propose a cost-effective disease-adapted closure of the appendicular stump employing the clip in standard appendectomies, with the endo-loop being a good alternative. If clip or loop cannot be applied the stapler is the technique of choice. In particular, it should be used if the base of the appendix is inflamed. Adopting this pathway helps to control the still somewhat higher costs of laparoscopic appendectomies compared to classical open appendectomies.
    Zentralblatt für Chirurgie 03/2012; · 1.02 Impact Factor
  • Article: [Consequences drawn from the evaluation of logbook-based surgical training for final year students].
    A Busemann, W von Bernstorff, C-D Heidecke
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    ABSTRACT: The current training programme for final year medical students does not meet the requirements of surgery and is obviously not able to encourage young physicians to become surgeons. After finishing the surgical trimester, the motivation to become a doctor decreases considerably more strongly than after any other specialty during the final year programme. This emphasises the urgent need for a consequent redesign involving modern educational programmes. The present article represents a systematic analysis of 70 logbooks used by final year medical students, which accompanied them during the surgical trimester from August 2008 to December 2009 at the Department of Surgery at the University of Greifswald, Germany. This analysis was subsequently compared to an evaluation of the same students as to how valuable the logbook was for their surgical education by means of an anonymous questionnaire. The results indicate that the general quality of education during the surgical trimester was evaluated to be high, but that the use of a logbook in the current mode did not contribute to enhance medical/surgical training programmes. Although most of the requested examinations and procedures were carried out by at least 70 % of the students, less than half of them had the impression that the use of this specific logbook improved their education. The students ask for a more intense interaction with the tutor/mentor and request differentiated discussions about their personal stronger and weaker spots, as well as more bedside teaching, e. g., the terms of training ward rounds with the consultant surgeon. Besides, they demand more supervised practical skill training in contrast to the often commonly practiced "learning by doing". The logbook is a powerful and effective educational tool able to structure and examine medical training and skills. But the present evaluation of the surgical logbook indicates that there is a need to adapt the current version to student's and institution's requirements. Otherwise it will only be seen as a purely labour intensive obligation, which will consequently lead to frustration and will not enrich the surgical training programme within the final year of medical school.
    Zentralblatt für Chirurgie 07/2011; 137(2):165-72. · 1.02 Impact Factor
  • Article: A syngeneic orthotopic murine model of pancreatic adenocarcinoma in the C57/BL6 mouse using the Panc02 and 6606PDA cell lines.
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    ABSTRACT: To develop a clinically relevant immunocompetent murine model to study pancreatic cancer using two different syngeneic pancreatic cancer cell lines and to assess MRI for its applicability in this model. Two cell lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation and migration were monitored in vitro. Matrigel™ was tested for its role in tumor induction. Tumor cell growth was assessed after orthotopic injection of tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology. Proliferation and migration of Panc02 were significantly faster than those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented tumor cell spread after injection thus avoiding undesired peritoneal tumor growth. MRI could reliably monitor longitudinal tumor growth in both cell lines: Panc02 had a more irregular finger-like growth, and 6606PDA grew more spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a moderately differentiated glandular tumor growth. Panc02 mice had a significantly shorter (28 days) survival than 6606PDA mice (50 days). This model closely mimics human pancreatic cancer. MRI was invaluable for longitudinal monitoring of tumor growth thus reducing the number of mice required. Employing two different cell lines, this model can be used for various treatment and imaging studies.
    European Surgical Research 06/2011; 47(2):98-107. · 0.93 Impact Factor

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