A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer.

BACKGROUND: We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide. CASE PRESENTATION: We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood. CONCLUSION: Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.

Banana leaves as an alternative wound dressing.

BACKGROUND: There is a need for cheap and efficacious wound dressings in developing countries. Banana leaves have been described as an excellent, inexpensive, easily available dressing material in tropical countries. As a natural product, banana leaves are heavily contaminated with various pathogens that must be removed before they can be used as wound dressings, but effective sterilization methods that do not affect the beneficial wound-dressing properties of banana leaves have not been described. OBJECTIVES: To study different sterilization methods and determine which can be used on banana leaves without affecting their beneficial wound-dressing properties. MATERIALS AND METHODS: We first compared the use of different decontamination techniques to reduce the natural microflora of the leaves and then tested the wound-dressing properties of the leaves in a mouse model of skin transplantation and in postsurgical patients in Uganda, Africa. RESULTS: Steam sterilization proved to be the optimal sterilization technique. Banana leaves displayed wound-dressing properties that equaled those of petroleum jelly gauze dressings and were tested successfully in a clinical setting in postsurgical patients in Uganda, Africa. CONCLUSION: We found banana leaves to be an excellent alternative wound dressing, combining the desirable properties of modern wound-dressing material with low cost.

Confocal laser scanning microscopy vs 3-dimensional histologic imaging in basal cell carcinoma.

OBJECTIVE: To compare ex vivo confocal laser scanning microscopy (CLSM), which offers rapid images without the need for tissue processing, vs 3-dimensional histologic imaging, the criterion standard treatment for basal cell carcinomas in high-risk areas of the face. DESIGN: Single-center prospective trial. SETTING: Dermatosurgical unit of a university hospital. Patients Seventy-two consecutive surgically removed basal cell carcinomas were examined using CLSM vs standard paraffin-embedded 3-dimensional histologic imaging. Interventions A total of 312 images, including 73 midsections, 196 lateral margins, 23 "muffins," and 20 "bread loaf sections," were obtained using CLSM. Immediately after surgery, the CLSM images were evaluated by the surgeon. The following day, the 3-dimensional histologic slides were evaluated and compared with the CLSM images. MAIN OUTCOME MEASURES: Diagnostic accuracy of ex vivo CLSM to detect tumor strands of basal cell carcinomas and the practicality of using CLSM vs 3-dimensional histologic slides in micrographic surgery. RESULTS: The sensitivity of CLSM reached 94.0% in midsections, 73.7% in lateral margins, 80.0% in muffins, and 80.0% in bread loaf sections. The CLSM images were evaluated by the surgeon within 7.5 minutes. CONCLUSIONS: Confocal laser scanning microscopy lacks high sensitivity to detect small tumor strands of basal cell carcinomas. In the future, CLSM may represent a time-saving and less expensive alternative to cryostat histopathologic examination.

Dysplastic nevus syndrome with development of multiple melanomas. A surgical concept for prophylaxis.

A 58-year-old man presented in 2001 with dysplastic nevus syndrome with at least 300 nevi and about 100 clinically highly atypical nevi. Three melanomas had been excised by a private dermatologist within the past year. We then removed two additional melanomas. Between 2002 and 2003, 117 nevi which were atypical on dermatoscopy were removed; most by horizontal (shave) excision. Adequate clinical and dermatoscopic control was not feasible due to the large number of atypical nevi. In order to reduce the number of nevus cells, we treated test sites with both dermabrasion and split-thickness excision. The latter proved to be more efficient and was used to completely excise the skin of the back, as well as parts of the arms and chest in two sessions under general anesthesia. Wound healing was uneventful. Following these procedures, adequate clinical and dermatoscopic monitoring of the remaining nevi was possible and only a few had to be removed. No more melanomas appeared in the treated areas.

Cosmetic results of histographically controlled excision of non-melanoma skin cancer in the head and neck region.

BACKGROUND: Beside the primary goal of complete eradication, the cosmetic result is an important aspect of the treatment of non-melanoma skin tumors especially in the head and neck region. PATIENTS AND METHODS: From 1990 to 2000, we treated a total of 5,227 large basal cell carcinomas (BBC) and 1,189 squamous cell carcinomas (SCC) in the head and neck region by surgical excision in 4,239 inpatients at the Department of Dermatology, University of Tübingen. The procedure used in all patients was a conservative excision controlled by complete three dimensional histology of all margins (3D-histology) and specifically targeted follow-up surgery where required (histographic surgery). As part of the prospective tumor follow-up, we asked the treating outdoor physician one and four years later to evaluate the results of our surgical procedures. RESULTS: Of the 5,565 follow-up questionnaires sent back, 4,868 contained answers regarding the cosmetic result. The data from both answers were pooled. In 1,972 (40,5 %) patients the cosmetic result was evaluated as "excellent", in 1,992 (40,9%) as "good", in 662 (13,6%) as "satisfactory", in 191 (3,9%) as "mediocre" and in 51 (< 1,0%) as "poor". In 697 of the responses, the physician did not comment the cosmetic results or the patient was lost for follow up. CONCLUSION: With respect to both long term safety and cosmetic outcome, tumor surgery with 3D-histology of excisional margins has set very high quality standards in the treatment of non-melanoma skin cancer of the head and neck area.

"Functional" surgery in subungual melanoma.

BACKGROUND: Subungual melanomas represent approximately 2% to 3% of cutaneous melanomas in White populations. Complete or partial amputation proximal to the distal interphalangeal joint of the digits has been suggested. Recently, we introduced for acral melanomas, similar to lentigo maligna melanoma, limited excision and complete histology of excisional margins (three-dimensional histology). OBJECTIVE: To evaluate the prognostic relevance of clinical parameters and different surgical management in patients with subungual melanoma. STUDY DESIGN: From 1980 to 1999, subungual melanoma was diagnosed in 62 of 3,960 stage I and II melanoma patients (1.6%) of the melanoma registry of the Department of Dermatology (University of Tuebingen). A retrospective comparative analysis of two treatment groups was performed: Thirty-one patients had an amputation in or proximal to the distal interphalangeal joint (median follow-up of 55 months), and 31 patients had "functional" surgery with local excision of the tumor and only partial resection of the distal phalanx (median follow-up of 54 months). RESULTS: In the univariate analysis, the level of invasion (P=0.0059), ulceration (P=0.0024), and tumor thickness (P=0.0004) were significant prognostic factors for recurrence-free survival but not for survival. In a multivariate analysis, only lower tumor thickness and a reduced level of amputation were independent significant prognostic parameters for recurrence-free survival (P=0.035 and P=0.0069). Patients with an amputation in or proximal to the distal interphalangeal joint did not fare better than patients with less radical "functional" surgery. CONCLUSION: Limited excision with partial resection of the distal phalanx only and three-dimensional histology to assure tumor-free resection margins give better cosmetic and functional results and do not negatively affect the prognosis of patients with subungual melanoma.