Dermatosurgery - from surgical option to integral part of dermatologic therapy.

Dermatosurgery was long considered an isolated, and not always important, discipline within dermatology. As a therapeutic option, it was considered either the gold standard of first-line therapy, for example in basal cell carcinoma surgery and treatment of early-stage melanoma, or the last option, for instance in the treatment of warts. The fact that a profound change has taken place and that dermatosurgery is now an integral, equal, sometimes leading and always significant component of dermatology will be demonstrated in this review using three examples from geriatric dermatology, the treatment of hidradenitis suppurativa (acne inversa), and melanoma therapy. This review is supplemented by a section on the most important technique in dermatosurgery: microscopic (micrographic) surgery or Mohs Surgery.

B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma.

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Current theories on regulation of inflammation center on anti-tumor T cell responses. Here we show that tumor associated B cells are vital to melanoma associated inflammation. Human B cells express pro- and anti-inflammatory factors and differentiate into plasmablast-like cells when exposed to autologous melanoma secretomes in vitro. This plasmablast-like phenotype can be reconciled in human melanomas where plasmablast-like cells also express T cell-recruiting chemokines CCL3, CCL4, CCL5. Depletion of B cells in melanoma patients by anti-CD20 immunotherapy decreases tumor associated inflammation and CD8+ T cell numbers. Plasmablast-like cells also increase PD-1+ T cell activation through anti-PD-1 blockade in vitro and their frequency in pretherapy melanomas predicts response and survival to immune checkpoint blockade. Tumor associated B cells therefore orchestrate and sustain melanoma inflammation and may represent a predictor for survival and response to immune checkpoint blockade therapy.

The EGF A61G polymorphism is associated with disease-free period and survival in malignant melanoma.

An earlier study reported that a common polymorphism in the 5' untranslated region of the epidermal growth factor (EGF) gene is associated with increased risk for cutaneous malignant melanoma (MM) and Breslow thickness. Since then, several independent studies have reported conflicting results that have challenged this hypothesis. However, none of the previous studies examined survival as the primary outcome. We therefore sought to study the association between this polymorphism and survival. One hundred and thirty patients diagnosed with MM with a Breslow thickness of >1.5 mm were included in this study. In our collective, the G/G genotype represented a significant risk factor for both shorter disease-free period (hazard ratio of 2.246, 95% CI: 1.06-4.78, P=0.036) and overall MM-specific survival (hazard ratio of 3.8, 95% CI: 1.5-9.5, P=0.004) compared with the A/A genotype, while the heterozygous A/G genotype showed an intermediate risk. In the present study, we demonstrate for the first time that the EGF A61G polymorphism is associated with survival. Our data suggest that this polymorphism is a potential marker for disease severity that predicts earlier progression of MM.

The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic behavior in human melanoma cells.

Melanoma is one of the most aggressive neoplastic transformations and characterized by a high metastatic potential. The current study was performed to assess the impact of "spleen tyrosine kinase" (Syk), a non-receptor-associated tyrosine kinase, on growth and metastatic behavior of melanoma cells in vitro and in a severe combined immunodeficient (SCID)-mouse/human-melanoma xenotransplantation model in vivo. Syk was expressed in melanocytes but was found to be downregulated in melanoma cells. Vector-driven expression of Syk in two different melanoma cell lines did not influence growth speed, but significantly reduced the invasive growth potential of both cell lines in a Matrigel assay in vitro. In a SCID-mouse/human melanoma xenotransplantation model, Syk expressing Mel-Juso cells exhibited delayed and reduced tumor growth. After intravenous as well as subcutaneous injection of tumor cells, Syk-transfected cells formed significantly fewer metastatic tumor lesions than control cells. The presented data define Syk as a novel regulator of metastatic behavior of melanoma cells.

Loss of novel mda-7 splice variant (mda-7s) expression is associated with metastatic melanoma.

Expression of melanoma differentiation associated gene-7 (mda-7) also known as interleukin 24 (IL-24) decreases during melanoma cell differentiation and induces apoptosis in melanoma cells but not in melanocytes. Here we identify a novel splice variant of the cancer growth suppressor gene mda-7/IL-24 (mda-7s) that is differentially expressed in RNA preparations from normal human melanocytes, transformed melanocytes, nevi, subcutaneous metastasis, lymph node metastasis, and melanoma cell lines. The 450 bp mda-7s mRNA encodes a protein of 63 residues with a molecular weight of 12 kDa. mda-7s lacks exons 3 and 5 of the full-length transcript and contains only 14 amino acids of homology to MDA-7 located within the signal peptide region of the wild-type sequence. Despite minimal homology, MDA-7S coprecipitates full length MDA-7 and reduces secretion of cotransfected MDA-7. mda-7 and mda-7s are coexpressed in all RNA preparations other than subcutaneous and lymph node metastasis where mda-7s expression is lacking. mda-7s expression is therefore linked to a non-metastatic phenotype.

Anal human papillomavirus testing with Digene's hybrid capture 2 using two different sampling methods.

PURPOSE: The incidence of human papillomavirus detection in the anal canal is rising. Efficient anal screening by cytology is hampered because of poor specificity. Human papillomavirus (HPV) testing is proposed in addition to Papanicolaou (Pap) testing for the detection of cervical neoplasia. The purpose of this study was to determine the usefulness of a human papillomavirus-DNA detection test to detect human papillomavirus-associated disease and to compare two different methods of sample collection. METHODS: In 555 patients, anal samples were obtained by using a cervical brush and a Dacron swab to test for high-risk and low-risk human papillomavirus-DNA. Patients positive for human papillomavirus-DNA underwent anoscopy. Biopsies were taken from visible lesions. RESULTS: Low-risk human papillomavirus-DNA was found in 325 of 555 patients (58.6 percent) and high-risk human papillomavirus-DNA in 285 of 555 patients (51.4 percent). Positive results confined to one single test method were higher for Dacron swab sampling (2.3 vs. 4.3 percent for low-risk human papillomavirus, P < 0.0001; 3.1 vs. 4.9 percent for high-risk human papillomavirus, P < 0.001). A positive correlation of relative light units was found for both sampling methods in the total cohort (P < 0.0001) as well as for patients who tested human papillomavirus-positive by both sampling techniques (P < 0.0001). Sampling with Dacron swabs yielded higher relative light units values compared with sampling with cervical brush for low-risk human papillomavirus-DNA and high-risk human papillomavirus-DNA. CONCLUSIONS: Anal screening for human papillomavirus-DNA by hybrid capture 2 is a useful method for detection of human papillomavirus-associated disease. Sample collection using Dacron swabs identifies more human papillomavirus-positive patients, and yields higher relative light unit values than using the cervical brush. Further studies are needed to determine the exact value of hybrid capture 2 in the screening for (pre)cancerous lesions of the anal canal.

Mid-term recurrence rate of incompetent perforating veins after combined superficial vein surgery and subfascial endoscopic perforating vein surgery.

BACKGROUND: This study investigated the mid-term (mean, 3.7 years) clinical results and the results of duplex Doppler sonographic examinations of subfascial endoscopic perforating vein surgery (SEPS) in patients with mild to severe chronic venous insufficiency (clinical class 2-6) and assessed the factors associated with the recurrence of insufficient perforating veins (IPVs). METHODS: Eighty patients with mild to severe chronic venous insufficiency undergoing SEPS were evaluated, and duplex findings, as well as clinical severity and disability scores before and after the operation, were compared. Patients with prior deep vein thrombosis (<6 months) or prior SEPS were excluded from this study. RESULTS: There were 27 men and 53 women with a median age of 59.8 years (range, 34.3-80.0 years). The distribution of clinical classes (CEAP) was as follows: class 2, 13.1% (12 limbs); class 3, 22.8% (21 limbs); class 4, 19.6% (18 limbs); class 5, 21.7% (20 limbs); and class 6, 22.8% (21 limbs). The etiology of venous insufficiency was primary valvular incompetence in 83 limbs (90.2%) and secondary disease in 9 limbs (9.8%). Concomitant superficial vein surgery was performed in 89 limbs (95.7%). Twenty (95%) leg ulcers healed spontaneously within 12 weeks after operation, whereas one patient required additional split-thickness skin grafting. Eighteen patients had previous surgery of the great and/or short saphenous vein before SEPS. During a mean follow-up of 3.7 years, recurrence of 22 IPVs was observed in 20 (21.7%) of 92 limbs, and recurrent leg ulcers were observed in 2 (9.5%) of 21 limbs. We performed univariate and multivariate analyses to predict factors influencing the recurrence of IPVs (recurrent superficial varicosis, secondary disease, active or healed leg ulcer [C5/6], compression treatment, and previous operation). On multivariate analysis, previous surgery (P = .014) was identified as the only significant factor for the recurrence of IPVs. CONCLUSIONS: SEPS is a safe and highly effective treatment for IPVs. Within a median follow-up period of 3.7 years, only 2 of 21 venous ulcers recurred, both in patients with secondary disease. Nevertheless, we observed recurrence of IPVs in 21.7% of the operated limbs. On multivariate analysis, patients who had undergone previous surgery were found to have a significantly higher rate of recurrence.