Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa.

BACKGROUND: In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. OBJECTIVES: To analyse the mRNA and protein expression of NCSTN, Notch1-3, PIK3R3 and AKT3 in HS. METHODS: Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. RESULTS: Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). CONCLUSION: We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS.

[Hidradenitis suppurativa /acne inversa-surgical options, reconstruction and combinations with drug therapies-an update]. / Hidradenitis suppurativa/Acne inversa ­ operative Optionen, Rekonstruktionen und Kombinationen mit medikamentösen Therapien ­ Ein Update.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease whose treatment includes both conservative and surgical treatment options. In Hurley stages II and III, surgical resection of irreversibly destroyed tissue should be the objective. For this purpose several resection techniques exist, which differ primarily with regard to their invasiveness and tendency to recur. To date, there is no generally accepted consensus on the use of different resection and reconstruction techniques or the inclusion of drug therapies in the overall therapeutic concept.

[Surgical treatment options for hidradenitis suppurativa/acne inversa]. / Operative Behandlungsoptionen bei Hidradenitis suppurativa/Acne inversa.

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Therapy consists of conservative and surgical treatment options. In Hurley stages II and III, surgical intervention is regarded as the method of choice for areas with irreversible tissue destruction. Resection techniques with different grades of invasiveness are described in the literature. Nevertheless, there is no generally accepted concept regarding resection and reconstruction techniques or specific postoperative care. Due to lack of definitions of recurrence after surgery and poor study quality, recurrence rates are difficult to determine.

[Ulcers in obesity-associated chronic venous insufficiency]. / Ulkus bei Adipositas-assoziierter chronischer Veneninsuffizienz.

BACKGROUND: Chronic venous insufficiency is a frequently occurring disease consisting of a characteristic symptom complex and ulcerations. Normally, varicose veins with reflux or obstruction can be found. However, these symptoms have also been described in obese people and are considered functional chronic venous insufficiency. The aim of this work was to present patients with ulceration in obesity-associated chronic venous insufficiency and to describe typical features of ulceration in obese people. MATERIALS AND METHODS: Seven patients with ulcerations of the lower limbs in obesity-associated chronic venous insufficiency were examined. Duplex sonography was performed; reflux or stenosis as well as a peripheral arterial occlusive disease could be excluded. RESULTS: In all, 7 patients presented with grade I-III obesity. The duplex sonographic examination showed no evidence of reflux or obstruction. However, multiple ulcers were found located on the proximal or ventrolateral lower limb. Most of them occurred posttraumatically or after insect bites with typical signs of chronic venous disease including hyperpigmentation and erythema. CONCLUSION: The cause of obesity-associated chronic venous insufficiency has been associated with an increased intraabdominal pressure due to abdominal fat masses. It leads to venous hypertension. Therapy consists of consequent compression therapy combined with suitable wound care, weight reduction, and regular exercise.

BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

BACKGROUND: Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. OBJECTIVES: We aimed to investigate Bim protein expression in cutaneous melanoma (CM). METHODS: Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. RESULTS: The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). CONCLUSIONS: Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target.

[Mental disorders in the general population : Study on the health of adults in Germany and the additional module mental health (DEGS1-MH)]. / Psychische Störungen in der Allgemeinbevölkerung : Studie zur Gesundheit Erwachsener in Deutschland und ihr Zusatzmodul Psychische Gesundheit (DEGS1-MH).

BACKGROUND AND OBJECTIVES: The German health interview and examination survey for adults (DEGS1) with the mental health module (DEGS1-MH) is the successor to the last survey of mental disorders in the general German population 15 years ago (GHS-MHS). This paper reports the basic findings on the 12-month prevalence of mental disorders, associated disabilities and self-reported healthcare utilization. METHODS: A representative national cohort (age range 18-79 years, n = 5,317) was selected and individuals were personally examined (87.5 % face to face and 12.5 % via telephone) by a comprehensive clinical interview using the composite international diagnostic interview (CIDI) questionnaire. RESULTS: The overall 12-month prevalence of mental disorders was 27.7 % with substantial differences between subgroups (e.g. sex, age, socioeconomic status). Mental disorders were found to be particularly impairing (elevated number of disability days). Less than 50 % of those affected reported to be in contact with health services due to mental health problems within the last 12 months (range 10-40 % depending on the number of diagnoses). CONCLUSIONS: Mental disorders were found to be commonplace with a prevalence level comparable to that found in the 1998 predecessor study but several further adjustments will have to be made for a sound methodological comparison between the studies. Apart from individual distress, elevated self-reported disability indicated a high societal disease burden of mental disorders (also in comparison with many somatic diseases). Despite a relatively comprehensive and well developed mental healthcare system in Germany there are still optimisation needs for treatment rates.

Histological findings after argon plasma coagulation: an ex-vivo study revealing a possible role in superficial ablative treatment of the skin.

Argon plasma coagulation (APC) is an electrosurgical technique which can be used to ablate skin lesions with limited invasion depth into dermal tissue. Hence, APC might be well suited for the removal of epithelial tumours. However, there are no data on the effects of APC on human skin tissue. Thus, the aim of this study was to determine the extent of epidermal and dermal damage after APC of human skin. We performed APC ex-vivo on 91 freshly resected human skin samples, which were obtained after reconstructive surgical closures in actinically damaged areas. Tissue effects were evaluated histologically and compared across different power settings. Using 15, 30, and 45 W, median (interquartile range; IQR) coagulation depths were 110.0 µm (91.7-130.0), 113.3 µm (85.8-135.0), and 130.0 µm (100.0-153.3.0), respectively. Median (IQR) thickness of necrosis zone was 30.0 µm (23.3-40.0) at 15 W, 26.7 µm (20.0-41.6) at 30 W, and 43.3 µm (30.8-57.5) at 45 W. The Kruskal-Wallis test showed significant differences between 15 and 30 W versus 45 W for coagulation depth (P = 0.0414), necrosis zone (P = 0.0017), and necrosis according to overlaying epidermal thickness (P = 0.0467). In summary, APC is a simple and controllable electrosurgical technique to remove epidermal tissue with limited penetration to the dermis. Thus, APC is particularly suited for the ablation of epithelial skin lesions and, therefore, may serve as possible treatment approach for intraepithelial neoplasms such as actinic keratosis.

Worse outcome for patients with recurrent melanoma after negative sentinel lymph biopsy as compared to sentinel-positive patients.

BACKGROUND: The long-term outcome of patients with melanoma who had recurrence after negative sentinel lymph node (SLN) biopsy has rarely been evaluated systematically. METHODS: We searched our databases for melanoma patients with SLN biopsy from the end of 1999 and the beginning of 2011. Data was analyzed using uni- and multivariate statistics as well as Kaplan-Meier curves. RESULTS: Data of 651 patients with melanoma was available for statistics. We observed 451 (69.3%) patients with negative SLN who had no evidence of disease recurrence during follow-up. Recurrence in SLN negative patients was found in 50 (7.7%) cases. Tumor subtypes such as invasive lentigo maligna melanoma and acral melanoma (odds ratio 15.2, P = 0.015) and tumor thickness > 2 mm (odds ratio 3.1, P = 0.0017) were independent predictors for recurrence in patients with negative SLN. Patients with negative SLN and subsequent recurrence had a significantly (P = 0.036) reduced 5-year melanoma-specific survival (MSS) when compared with positive SLN patients. Recurrence of disease in positive SLN patients was observed after a median of 39 months when compared to patients with negative SLN and recurrence (28 months, P = 0.0079). Negative SLN with recurrence was an independent predictor for worse recurrence free and melanoma-related survival. CONCLUSIONS: Patients with negative SLN and recurrence experience earlier disease relapses and poorer MSS when compared to patients with positive SLN status implicating that more stringent follow-up procedures are warranted in patients with higher tumor thickness and invasive lentigo maligna and acral melanoma, despite a negative SLN.