Autologous skin substitute for hard-to-heal ulcers: retrospective analysis on safety, applicability, and efficacy in an outpatient and hospitalized setting.

Chronic ulcers ((arterio)venous, decubitus, or postoperative) have no tendency to heal within a period of at least 3 months despite optimal therapy according to internationally accepted guidelines. This retrospective study evaluates the safety and efficacy of an autologous, dermal-epidermal skin substitute (SS) for treating ulcers of various origins. Ulcers were treated within 7 Dutch centers over 5 years. Sixty-six ulcers (size: 0.75-150 cm²; duration: 0.25-32 years) with a follow-up time of 24 weeks after a single-skin substitute application were assessed. Wound-bed preparation consisted of vacuum-assisted-closure-therapy (5 days, hospitalized) or application of acellular dermis (5-7 days, outpatient). Time to heal, adverse events, and recurrence 1 year after complete healing were recorded. Complete ulcer healing occurred in 36 of 66 ulcers (55%) at 24 weeks. At that time point, a further 29% of ulcers showed decrease in ulcer size between 50 and 99%. No difference was observed between the hospitalized vs. outpatient treatment with complete healing. There were 32 of 36 healed ulcers that were available for follow-up 1 year after complete closure, of which 27 (84%) were still closed. Only two minor/moderate possibly related adverse events were recorded. This retrospective analysis shows that SS provides a safe and successful treatment for particularly chronic ulcers of various origins.

Adenoid cystic carcinoma of the head and neck: a single-center analysis of 105 consecutive cases over a 30-year period.

BACKGROUND: Adenoid cystic carcinoma is a rare salivary gland malignancy with a poor disease free survival due to frequent distant metastases and late local recurrences. Previous single-center reports on outcome mostly encompass small series. In this report a relative large series of 105 cases is analyzed, all treated at the VU University Medical Center, Amsterdam, The Netherlands over a 30-year period in which treatment strategies remained unchanged. METHODS: All cases of ACC of the head and neck between 1979 and 2009 at our institution were analyzed through a medical chart review. Recurrence patterns and possible prognostic factors (T-stage, N-status, age, gender, type of salivary gland involved, histological grade, surgical margins, perineural invasion (PNI) and postoperative radiotherapy (RT)) were analyzed. RESULTS: One-hundred and five cases of ACC of the head and neck were identified. Five-, ten- and twenty-year survival rates for overall survival were 68%, 52% and 28%, respectively. T-stage, N-status, surgical margins, histological subtype and age were highly significant predictors for survival. PNI was not a negative prognosticator. CONCLUSIONS: T-stage, N-status, surgical margins, histological grade and age are the main predictors of survival-outcome in ACC of the head and neck. Distant metastasis frequently develop, mainly in the first 5 years post treatment. Local recurrences often develop even later on, warranting long term follow up of patients treated for ACC. Grade III ACC should be considered a specific entity within the group of ACC due to its typical aggressive biological behavior and relatively poor outcome, implicating the need for an improved adjuvant treatment.

Negative NKX2-1 (TTF-1) as temporary surrogate marker for treatment selection during EGFR-mutation analysis in patients with non-small-cell lung cancer.

INTRODUCTION: In the past decade, major progress has been made toward personalized medical treatment of non-small-cell lung cancer (NSCLC) through the discovery of epithelial growth factor receptor (EGFR) mutations. However, mutation analysis takes extra time and additional costs in the diagnostic evaluation of lung cancer patients. It has been hypothesized that EGFR mutations are restricted to terminal respiratory unit -type adenocarcinoma expressing thyroid transcription factor-1 (official symbol NKX2-1) as determined by immunohistochemistry. The aim of the current study is to evaluate the potential of NKX2-1 immunohistochemistry as a prescreening test for EGFR mutation analysis. METHODS: From 2004 to December 2010, 810 consecutive NSCLC tumor specimens were tested for EGFR mutations in a routine diagnostic procedure. Immunohistochemistry for NKX2-1 was performed (clone 8G7G3/1 [Dako]) and the results were compared with tumor EGFR-mutation status and clinicopathological characteristics. RESULTS: EGFR mutations were detected in 114 specimens (14%). NKX2-1 expression was present in 68%. In the cases with EGFR mutation, NKX2-1 staining was positive in 92%. NKX2-1 immunohistochemical (IHC) staining was significantly associated with the presence of EGFR mutations (p = 5.3×10). NKX2-1 increased the negative predictive value in NSCLC to more than 95%. CONCLUSIONS: In case of a negative NKX2-1 IHC staining, and only if clinically urgent, the high negative predictive value of more than 95% for EGFR mutations is a suitable temporary surrogate marker for the choice of starting with chemotherapy. In case of positive NKX2-1 IHC, the best strategy is to wait for the outcome of EGFR-mutation analysis and then choose the appropriate treatment.

The role of the skin irritation response in polysensitization to fragrances.

BACKGROUND: Contact allergy to fragrance chemicals is an increasing problem. Polysensitization is likely to be a phenotype of increased susceptibility to contact allergy. The factors that play a role in polysensitization are largely unknown. Identifying these risk factors is important with regard to future studies on the aetiology of contact allergy. OBJECTIVES: To investigate whether enhanced skin irritability is a risk factor for the development of polysensitization to fragrance chemicals. METHODS: One hundred participants characterized by fragrance contact allergy were included in our study. The participants were patch tested on the back with 25 individual fragrance chemicals and fragrance mixes I and II, and on the upper arm with sodium lauryl sulfate (SLS) (consisting of SLS concentrations of 0.45%, 0.67%, 1%, and 1.5%). Reading of both tests was performed during the following visits at days 2, 3, and 7. The response to SLS was monitored by measuring transepidermal water loss (TEWL). Polysensitization was defined as three or more allergic reactions to non-cross-reacting fragrance chemical allergens. RESULTS: Individuals with polysensitization showed significantly higher irritation responses to SLS 1% and 1.5% as assessed by TEWL. CONCLUSIONS: We found an enhanced skin irritation response to be a risk factor for the development of polysensitization to fragrance chemicals.