Fachklinik Hornheide

Bad Münster am Stein-Ebernburg, Germany

Fachklinik Hornheide

Bad Münster am Stein-Ebernburg, Germany
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Migden M.R.,University of Houston | Guminski A.,Royal North Shore Hospital | Gutzmer R.,Medizinische Hochschule Hanover | Dirix L.,Sint Augustinus Ziekenhuis | And 19 more authors.
The Lancet Oncology | Year: 2015

Background: Patients with advanced basal cell carcinoma have limited treatment options. Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma. Methods: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. Patients were randomised via an automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily, stratified by disease, histological subtype, and geographical region. The primary endpoint was the proportion of patients who achieved an objective response, assessed in the primary efficacy analysis population (patients with fully assessable locally advanced disease and all those with metastatic disease) with data collected up to 6 months after randomisation of the last patient. This trial is registered with ClinicalTrials.gov, number NCT01327053. Findings: Between July 20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib group, and 151 in the 800 mg sonidegib group. Median follow-up was 13·9 months (IQR 10·1-17·3). In the primary efficacy analysis population, 20 (36%, 95% CI 24-50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116 receiving 800 mg sonidegib achieved an objective response. In the 200 mg sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective response, as assessed by central review, were noted among the 42 with locally advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally advanced disease had an objective response, as assessed by central review, as did four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200 mg group than in the 800 mg group. The most common grade 3-4 adverse events were raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group. Interpretation: The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat. © 2015 Elsevier Ltd.

Teltzrow T.,Klinikum Ernst von Bergmann | Arens A.,Kaiserswerther Diakonie Krankenhaus | Schwipper V.,Fachklinik Hornheide
Facial Plastic Surgery | Year: 2011

Complex nasal defects in the distal regions of the nose are cosmetically difficult to repair. In 70 patients over a period of 10 years, defects of the nasal ala and the soft triangle, nasal tip, columella, and columellar-lobular junction were reconstructed with modified auricular composite grafts. A randomized group of 40 of these patients was assessed after a mean of 55.5 months to evaluate the method's functional and cosmetic long-term results. The majority of the patients (60%, n=48) had been treated primarily for basal cell carcinoma. Of all defects, 57% (n=46) measured 2 to 3 cm in width and 43% (n=34) 1 to 2 cm. Seventy-five percent (n=60) of all defects were composite lesions involving skin, cartilage, and vestibular mucosa, in contrast to 25% (n=20) involving skin and cartilage with intact vestibular skin. Two crucial technical modifications seemed to have improved survival for larger grafts: first, the use of hinge flaps from the margins of the defect to obtain a well-vascularized recipient bed and optimization of the raw contact surface; second, postoperative gentle scarification of the graft in combination with a constantly applied heparin solution decongests venous stasis normally seen in such grafts. This maneuver establishes a stable and early blood supply enhancing graft take. With this type of treatment, 67 (84%) grafts healed well without further complications, whereas 13 (16%) grafts developed complications, resulting in partial (n=9) and total (n=4) necrosis of the transplant. Six of these patients underwent a secondary reconstruction using another auricular composite graft. Long-term results of this method have turned out to be very satisfying in terms of functional and cosmetic outcome and patient acceptance. Copyright © 2011 by Thieme Medical Publishers, Inc.

Peters A.S.,University of Heidelberg | Brunner G.,Fachklinik Hornheide | Krieg T.,University of Cologne | Eckes B.,University of Cologne
Archives of Dermatological Research | Year: 2015

Many tissues are constantly exposed to mechanical stress, e.g. shear stress in vascular endothelium, compression forces in cartilage or tensile strain in the skin. Dermal fibroblasts can differentiate into contractile myofibroblasts in a process requiring the presence of TGFβ1 in addition to mechanical load. We aimed at investigating the effect of cyclic mechanical strain on dermal fibroblasts grown in a three-dimensional environment. Therefore, murine dermal fibroblasts were cultured in collagen gels and subjected to cyclic tension at a frequency of 0.1 Hz (6 cycles/min) with a maximal increase in surface area of 10 % for 24 h. This treatment resulted in a significant increase in active TGFβ1 levels, leaving the amount of total TGFβ1 unaffected. TGFβ1 activation led to pSMAD2-mediated transcriptional elevation of downstream mediators, such as CTGF, and an auto-induction of TGFβ1, respectively. © 2014, Springer-Verlag Berlin Heidelberg.

Schwipper V.,Fachklinik Hornheide
Facial Plastic Surgery | Year: 2011

In a retrospective study, initial diagnosis and method of treatment were evaluated in 118 patients with invasive basal cell carcinoma (formerly basalioma terebrans) of the head and neck. In 97 of the total 118 patients, radical surgery with resection of important organs had to be performed, and the follow-up results of 107 patients were recorded. In 44 (41%) of the latter 107 cases, recurrences were observed despite radical tumor excision, and only 63 (59%) patients were free of tumor. In 20 patients a second recurrence and in 12 patients a third recurrence was found. The recurrence rate amounted to only 1.9% in a comparative study group of 6932 patients with simple basal cell carcinoma. The findings reveal that healing without recurrence was achieved in only half of the patients with invasive basal cell carcinoma (basalioma terebrans). In cases in which bony structures had been invaded by the tumor, the recurrence rate was 71.4%. Despite the hypothesis of primary incurability of invasive basal cell carcinoma, it is pointed out that radical surgery may still improve a patient's quality of life. Although definite healing seems impossible, surgery may contribute to an acceptable quality of life for several years. Copyright © 2011 by Thieme Medical Publishers, Inc.

Lunatschek C.,University of Ulm | Schwipper V.,Fachklinik Hornheide | Scheithauer M.,University of Ulm
Facial Plastic Surgery | Year: 2011

Soft tissue repair of skin defects of the nosebeing in the middle of the faceis very demanding with regard to its functional and aesthetic outcome to allow successful rehabilitation of the patient concerned. In the majority of these cases, soft tissue reconstruction using local and regional flaps is indicated after individual therapy planning considering location and size of the defect, the patient's age, and his or her wishes. Flaps from nasal skin, glabella, forehead, as well as nasolabial fold provide good possibilities to cover the defect externally and ensure matching color and texture. Full-thickness skin grafts and healing by secondary intent are second-choice therapies. In the case of partial amputation of the nose, a nasolabial rotation flap can be used for inner lining, if necessary supported by septal cartilage or a composite graft building a stable nasal scaffold from the inside for the outside. The possibilities of facial plastic surgery, the exact knowledge of vascular supply, and flaps adjusted to individual requirements allow achievement of an outcome that is aesthetically and functionally satisfying for the patient. Copyright © 2011 by Thieme Medical Publishers, Inc.

Dugas-Breit S.,Fachklinik Hornheide | Schulze H.-J.,Fachklinik Hornheide | Hallermann C.,Fachklinik Hornheide
JDDG - Journal of the German Society of Dermatology | Year: 2014

At the time of diagnosis primary cutaneous lymphomas are limited to the skin. T-cell lymphomas represent at least two thirds of all primary cutaneous lymphomas with mycosis fungoides and Sézary syndrome being the most frequent entities. A precise staging based on clinical, histological, immunohistological and molecular biological criteria is crucial for selecting the appropriate therapy. Since curative treatment is only possible in exceptional cases, the aim of any therapy is to achieve healing of the skin lesions, minimizing relapses, preventing progression and maintaining the quality of life. While in early disease stages skin-directed therapy is being used, in later stages systemic treatments become more important. This work aims to provide an overview of established and new therapies for the treatment of mycosis fungoides and Sézary syndrome. © 2014 Deutsche Dermatologische Gesellschaft (DDG).

Losler A.,Fachklinik Hornheide | Kotthoff C.,Fachklinik Hornheide | Kruse-Losler B.,University of Munster
European Journal of Surgical Oncology | Year: 2014

The nasal region represents an important three-dimensional esthetic unit where minimal distortion will be obvious and disturbing. In this regard the reconstruction of the nasal ala in dermatologic tumor surgery may be challenging. We propose the reconstructive option of a caudal-lateral inserted transposition flap for this indication. The principle of this surgical alternative and the long-term outcome is demonstrated in representative cases. The various indications and modifications of this reconstructive principle are discussed and compared to other remodeling alternatives. © 2013 Elsevier Ltd. All rights reserved.

Hallermann C.,Fachklinik Hornheide | Schulze H.-J.,Fachklinik Hornheide
Hautarzt | Year: 2011

A 45-year-old woman presented with diffuse melanosis, icteric sclera and melanuria. Physical examination revealed a massive nodular melanoma with ulceration and satellite metastases on the back. Further investigation showed distant cutaneous and visceral metastasis. After palliative debulking along with postoperative multidrug chemotherapy, the patient has shown objective disease regression for more than 11 months. However, it remains to be seen if disease regression will translate into increased survival. © 2010 Springer-Verlag.

Borst A.,University of Munster | Schwipper V.,Fachklinik Hornheide
Facial Plastic Surgery | Year: 2011

Diagnosis, therapy, and prognosis of 40 patients with malignant melanoma of the mucous membranes, treated at one hospital from 1971 to 2006, were evaluated in a retrospective study. The survival rate was compared with that established by the German-Austrian-Swiss Study Group on Tumors of the Head and Neck (DSAK) for 121 cases. The cumulated 5-year survival rate amounting to 33% (DSAK study 35%) emphasizes the unfavorable prognosis of this tumor. Age, sex, or tumor location had no significant impact on a patient's survival. A modified surgical concept has been developed for the treatment of the primary tumor and its lymphatic drainage area to maintain a patient's quality of life. The entire tumor should be resected under histologic control ensuring a 5-mm safety margin of healthy tissue. Bone should only be resected if invaded by the tumor. Large resections of the upper or lower jaw should be avoided. A neck dissection does not improve the prognosis and should be performed only in the case of histologically confirmed invasion of lymph nodes. Copyright © 2011 by Thieme Medical Publishers, Inc.

Fluck M.,Fachklinik Hornheide | Garbe C.,University of Tübingen
Onkologe | Year: 2014

Background. For high-risk melanoma in stages II and III (thick primary tumors >2 mm tumor thickness and presence of locoregional metastases) there is a need for adjuvant therapy to reduce the recurrence and mortality risk. Material and methods. A literature search was performed in PubMed. Current adjuvant trials involving high-risk melanoma patients in Europe were identified in the database ClinicalTrials.gov. Results. Several randomized phase III studies have been conducted to find a successful adjuvant therapy. Studies with systemic chemotherapy and with nonspecific immunostimulants, such as Bacillus Calmette-Guérin (BCG) vaccination or mistletoe therapy were ineffective. An improvement of recurrence-free and overall survival was demonstrated in the 1990s only for interferon alpha therapy and a high-dose regimen was approved in the USA and Europe as well as a low-dose regimen in Europe. In Germany the low-dose regimen is mainly offered to stage II and III melanoma patients; however, the clinical benefit of this treatment is moderate and new trials are currently looking for more effective adjuvant therapies for melanoma. A European Organisation for Research and Treatment of Cancer (EORTC) study with the monoclonal cytotoxicT-lymphocyte antigen 4 (CTLA-4) antibody ipilimumab has already been completed in the recruitment stage, as well as a cancer vaccination study with the recombinant melanoma-associated antigen 3 (MAGE-A3) and a study with the anti-angiogenic antibody bevacizumab. Furthermore, two studies were launched with kinase inhibitors, a study with the BRAF inhibitor vemurafenib and a study with the combination of the BRAF inhibitor dabrafenib and the mitogen-activated protein kinase (MEK) inhibitor trametinib. Conclusion. It remains to be seen whether one or more of these treatments will show better efficacy than interferon alpha, and whether changes in the adjuvant therapy of melanoma will prevail in the coming years. © 2014 Springer-Verlag.

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