The bidirectional tumor - mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Introduction: Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor-derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells. Methods: MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model. Results: Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1α. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model. Conclusions: This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo

Microsurgical reconstruction of the head and neck-Current practice of maxillofacial units in Germany, Austria, and Switzerland

Refinement in microvascular reconstructive techniques over the last 30 years has enabled an increasing number of patients to be rehabilitated for both functional and aesthetic reasons. The purpose of this study was to evaluate different microsurgical practice, including perioperative management, in Germany, Austria, and Switzerland. The D`OSAK collaborative group for Microsurgical Reconstruction developed a detailed questionnaire which was circulated to units in the three countries. The current practice of the departments was evaluated. Thirty-eight questionnaires were completed resulting in a 47.5% response rate. A considerable variation in the number of microsurgical reconstructions per year was noted. In relation to the timing of bony reconstruction, 10 hospitals did reconstructions primarily (26.3%), 19 secondarily (50%) and 9 (23.7%) hospitals used both concepts. In the postoperative course, 15.8% of hospitals use inhibitors of platelet aggregation, most hospitals use low molecular heparin (52.6%) or other heparin products (44.7%). This survey shows variation in the performance, management, and care of microsurgical reconstructions of patients. This is due in part to the microvascular surgeons available in the unit but it is also due to different types of hospitals where various types of care can be performed in these patients needing special perioperative care. textcopyright 2010 European Association for Cranio-Maxillo-Facial Surgery

A worldwide comparison of the management of T1 and T2 anterior floor of the mouth and tongue squamous cell carcinoma - Extent of surgical resection and reconstructive measures

Introduction Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German-speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue. Methods The DOESAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. Results A total of 188 OMFS units from 36 different countries documented their treatment strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of the tumor versus continuity resection of the mandible and reconstruction ranging from locoregional closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform. Conclusion These results demonstrate the lack of evidence and the controversy of different guidelines for the extent of safety margins and underline the crucial need of global prospective randomized trials on this topic to finally obtain evidence for a common guideline based on a strong community of OMFS units

A worldwide comparison of the management of surgical treatment of advanced oral cancer

Introduction: Microvascular surgery following tumor resection has become an important field of oral and maxillofacial surgery (OMFS). Following the results from management of T1/T2 floor-of-mouth and tongue squamous cell carcinoma (SCC) in German-speaking countries, Europe, and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T3/T4 SCC of the maxillary and mandibular alveolar process and tongue. Methods: The D`OSAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. Results: A total of 188 OMFS units from 36 different countries documented their treatment strategies for T3/T4 maxillary and mandibular alveolar process and tongue SCC. The extent of surgical resections and subsequent reconstructions is more consistent than with T1/T2 tumors, although the controversy surrounding continuity resections and mandible-sparing procedures remains. For continuity resection of the mandible the fibula free flap is the most frequently used bone replacement, whereas maxilla reconstruction concepts are less consistent, ranging from locoregional coverage concepts and different microvascular reconstruction options to treatment via obturator prosthesis. Conclusion: Results from treatment strategies for T3/T4 tumors underline the limited evidence for the appropriate amount of resection and subsequent reconstruction process, especially in cases involving the mandible. Prospective randomized trials will be necessary in the long term to establish valid treatment guidelines

Schädigung des respiratorischen Epithels durch Zinkoxid-Nanopartikelexposition?

Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the surveys on current reconstructive practice in German-speaking countries and Europe, this paper presents the third phase of the project when the survey was conducted globally. The DOESAK questionnaire has been developed via a multicenter approach with maxillofacial surgeons from 19 different hospitals in Germany, Austria and Switzerland. It was distributed in three different phases to a growing number of maxillofacial units in German-speaking clinics, over Europe and then worldwide. Thirty-eight units from Germany, Austria and Switzerland, 65 remaining European OMFS-departments and 226 units worldwide responded to the survey. There is wide agreement on the most commonly used flaps, intraoperative rapid sections and a trend towards primary bony reconstruction. No uniform concepts can be identified concerning osteosynthesis of bone transplants, microsurgical techniques, administration of supportive medication and postoperative monitoring protocols. Microsurgical reconstruction is the gold standard for the majority of oncologic cases in Europe, but worldwide, only every second unit has access to this technique. The DOESAK questionnaire has proven to be a valid and well accepted tool for gathering information about current practice in reconstructive OMFS surgery. The questionnaire has been able to demonstrate similarities, differences and global inequalities

Microsurgical reconstruction of the head and neck--current concepts of maxillofacial surgery in Europe

Introduction Microvascular surgery following tumour resection has become an important field of oral maxillofacial surgery (OMFS). This paper aims to evaluate current microsurgical practice in Europe. Methods The questionnaire of the DOESAK collaborative group for Microsurgical Reconstruction was translated into English, transformed into an online based survey and distributed to 200 OMFS units with the aid of the European Association for Cranio-Maxillo-Facial Surgery (EACMFS). Results 65 complete and 72 incomplete questionnaires were returned. Hospitals from the United Kingdom, France, Italy, the Netherlands, Spain, Belgium, Greece, Slovenia and Lithuania participated. 71% of contributing centres were university hospitals, 87% out of these perform microvascular tumour surgery at least on a two-weekly base. Overall complication rate was at around five percent. Most frequently used transplants were the radial forearm flap and the fibular flap. The perioperative management varied widely. Success factors for flap survival, however, were uniformly rated, with the surgical skill being the most important factor, followed by the quality of postoperative management. Medication seems to play a less important role. Conclusion Within Europe microvascular surgery is a common and safe procedure for maxillofacial reconstructive surgery in the field of OMFS. While there is a major accordance for the surgical procedure itself and the most frequently used flaps, perioperative management shows a wide variety of protocols with low presumed impact on surgical outcome