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BackgroundDespite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.MethodsPatients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).ResultsOf 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwtpatients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmutpatients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmutpatients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmutpatients. In BRAFwtpatients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwtpatients. For BRAFmutpatients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.ConclusionsIn BRAFmutpatients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwtpatients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1.

Infektionen mit humanen Papillomviren (HPV) sind bei sexuell aktiven Menschen sehr haufig, verlaufen jedoch uberwiegend asymptomatisch. Von den bislang mehr als 200 komplett klassifizierten HPV-Typen gehoren etwa 40 zum Genus Alpha und fuhren uberwiegend zu Infektionen des Anogenitalbereichs. Condylomata acuminata werden durch Low-risk-HPV-Typen verursacht und zahlen zu den haufigsten sexuell ubertragenen Erkrankungen. Hochgradige anale Dysplasien sind potenzielle Vorlauferlasionen invasiver Analkarzinome und werden durch High-risk-HPV-Typen ausgelost. Da es sich um intraepitheliale Lasionen handelt, sollte die Behandlung von Condylomata acuminata und analen Dysplasien immer gewebeschonend und oberflachlich erfolgen. Die Therapiemoglichkeiten fur Condylome und anale Dysplasien unterscheiden sich nicht wesentlich und konnen in ablative und topische Verfahren unterteilt werden. Condylomata acuminata und ein wesentlicher Anteil analer Dysplasien sind durch die prophylaktische HPV-Impfung verhinderbar. Bei bereits erfolgter HPV-Infektion bzw. vorhandenen HPV-induzierten Lasionen kann eine prophylaktische HPV-Impfung nicht empfohlen werden.

Pruritus ani (analer Juckreiz) ist ein in der Praxis haufig auftretendes Symptom, das bei Chronifizierung mit hohem Leidensdruck einhergeht. In der Regel tritt analer Pruritus sekundar als Symptom verschiedener Krankheitsbilder, u. a. aus dem Spektrum dermatologischer, proktologischer, allergologischer oder mikrobieller Erkrankungen, auf. Die Identifikation und spezifische Behandlung der zugrundeliegenden Ursache ist in diesen Fallen essenziell. Lasst sich keine zugrundeliegende Erkrankung eruieren, spricht man von einem idiopathischen (primaren) Pruritus ani. Wie auch bei der Behandlung des Analekzems hangt der mittel- und langfristige Therapieerfolg im Management des Pruritus ani von verschiedenen Elementen der Behandlung ab, die sich grob in kausale, unterstutzende und symptomatische Masnahmen unterteilen lassen. Im vorliegenden Beitrag werden u. a. die Empfehlungen der aktualisierten Leitlinie „Analer Pruritus“ (AWMF-Reg. 013/063) vorgestellt.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Perianal dermatitis (anal eczema, perianal eczema) is one of the most common proctological conditions. It may occur as a sequela or a presenting symptom of various proctological, dermatological, allergic or pathogen-induced disorders. The three main types of anal eczema are irritant-toxic, atopic and allergic contact dermatitis. Adequate and successful treatment requires a comprehensive diagnostic workup to determine disease etiology and includes treatment/elimination of causative factors as well as nonpharmacological interventions (avoidance of aggravating factors). In addition, adjuvant topical anti-inflammatory and/or specific symptomatic treatment may be required. The present guidelines contain recommendations for the diagnostic and therapeutic management of perianal dermatitis. Target users of these guidelines are clinicians in the fields of dermatology and proctology, as well as all other specialties involved in the management of patients with perianal dermatitis, both in hospital and office-based settings.

BackgroundDespite of various therapeutic strategies, treatment of patients with melanoma brain metastasis (MBM) still is a major challenge. This study aimed at investigating the impact of type and sequence of immune checkpoint blockade (ICB) and targeted therapy (TT), radiotherapy, and surgery on the survival outcome of patients with MBM.MethodWe assessed data of 450 patients collected within the prospective multicenter real-world skin cancer registry ADOREG who were diagnosed with MBM before start of the first non-adjuvant systemic therapy. Study endpoints were progression-free survival (PFS) and overall survival (OS).ResultsOf 450 MBM patients, 175 (38.9%) received CTLA-4+PD-1 ICB, 161 (35.8%) PD-1 ICB, and 114 (25.3%) BRAF+MEK TT as first-line treatment. Additional to systemic therapy, 67.3% of the patients received radiotherapy (stereotactic radiosurgery (SRS); conventional radiotherapy (CRT)) and 24.4% had surgery of MBM. 199 patients (42.2%) received a second-line systemic therapy. Multivariate Cox regression analysis revealed the application of radiotherapy (HR for SRS: 0.213, 95% CI 0.094 to 0.485, p1 cm: 1.977, 95% CI 1.117 to 3.500, p=0.019), age (HR for age >65 years: 1.802, 95% CI 1.016 to 3.197, p=0.044), and ECOG performance status (HR for ECOG ≥2: HR: 2.615, 95% CI 1.024 to 6.676, p=0.044) as independent prognostic factors of OS on first-line therapy. The type of first-line therapy (ICB vs TT) was not independently prognostic. As second-line therapy BRAF+MEK showed the best survival outcome compared with ICB and other therapies (HR for CTLA-4+PD-1 compared with BRAF+MEK: 13.964, 95% CI 3.6 to 54.4, pConclusionsIn patients with MBM, the addition of radiotherapy resulted in a favorable OS on systemic therapy. In BRAF-mutated MBM patients, ICB as first-line therapy and BRAF+MEK as second-line therapy were associated with a significantly prolonged OS.

Background: Skin cancer removal surgery involving the tip or dorsum of the nose often results in large-sized defects with exposure of cartilage. In such cases, the paramedian forehead flap is a frequently used reconstruction technique; however, this method is complex and can result in a cosmetically unsatisfying outcome. Objective: To describe the folded transposition flap as an aesthetically pleasing alternative to the paramedian forehead flap for large nasal defects with exposed cartilage. Methods: The folded transposition flap is a 2-stage surgical modification of the transposition flap. In the first stage, an overlong axial cheek pedicle is used to cover the defect. In the second stage, the flap is thinned and the nasal scars are revised. Results: All 4 patients experienced aesthetically pleasing results. Conclusion: The folded transposition flap is an alternative for reconstructing large surgical defects of the nasal tip or distal dorsum of the nose.

Background Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. Methods A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. Results A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7%). The rate of lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. Conclusions The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.

Somatic mutations in the MYD88 gene are involved in the molecular pathogenesis of different subtypes of Non-Hodgkin B-cell lymphomas such as diffuse large B-cell lymphoma, lymphoplasmacytic lymphoma and Waldenstrom′s macroglobulinemia1. Albeit with much lower frequency, the key driver mutation MYD88 (c.794T>C, p.L265P) has also been identified in non-cutaneous marginal zone lymphomas and chronic lymphocytic leukemia. The increasing knowledge about such molecular aberrations and their consecutive biological effects has already been implemented within the clinical routine. This article is protected by copyright. All rights reserved.

Multilayer argon plasma coagulation (APC) is a new effective method for the treatment of genital warts. We assessed the generation of aerosols containing human papilloma virus (HPV) DNA during treatment of genital warts with multilayer APC and with CO2 laser ablation. Surveillance petri dishes, swabs from the glasses and nasolabial folds of the operating physician, and swabs taken from the suction units used during CO2 laser ablation were tested by HPV PCR. HPV DNA corresponding to patient derived HPV types of genital warts was not found in any of the petri dishes and swabs obtained during APC treatment. HPV DNA was detected in none of the petri dishes obtained during CO2 laser treatment, but in suction filters. In conclusion, both CO2 laser ablation with plume suction and APC treatment seem to have a low risk of HPV contamination of the operation room.

Split-skin grafting is a routine reconstructive technique associated with large variation in practice. Grafts from the thigh, buttock, or abdomen take a long time to heal and may leave unpleasant, hypopigmented scars. Retrospective reports favor the scalp as a donor site in burn patients.Evaluation of duration of healing, cosmetic outcome, and safety of split-skin grafting from the scalp in patients receiving dermatologic surgery.One hundred sixty-six consecutive patients (85 men, 81 women) were treated for coverage of chronic leg ulcers or other large skin defects with a split-skin graft taken from the posterior scalp. Area and thickness of the graft, healing time, and adverse events were documented.Mean healing time until complete reepithelization was 5.4+/-1.0 days for a single harvest (median 5 days). No major complications occurred. Spotted alopecia was a rare event. Almost all (96.5%) of the patients would undergo split-skin harvesting from the occipital scalp again if needed.Advantages of the scalp as a donor site include rapidity of wound healing, low risk of complications, and excellent cosmetic results. The large number of hair follicles containing the epidermal stem cell pool can explain these advantages.

Die endoanale Sonographie wird als wenig invasives Verfahren zur Lokalisation von Verletzungen des Sphinkterapparates und in der Dia gnostik von Fisteln und Abszessen eingesetzt. Schallkopfnahe Strukturen haben in der sonographischen Betrachtung des Analkanals wenig Beachtung gefunden, da sie zumeist der klinischen Untersuchung besser zuganglich scheinen und bei der endoanalen Sonographie mit groseren Schallkopfen durch Kompression nur eingeschrankt beurteilbar sind. Ziel der vorliegenden Untersuchung war es, die diagnostische Wertigkeit der analen Endosonographie mit einem 7-mm-Schallkopf zu evaluieren. In den letzten 4 1/2 Jahren untersuchten die Autoren 47 Patienten mit dem klinischen Verdacht auf Abszess-/Fistelleiden, Fissur oder Raumforderung im analen Kanal. Diese Patienten wurden mit einem 7 mm grosen endoanalen Schallkopf und, wenn moglich, mit einem 20 mm grosen endoanalen Schallkopf untersucht. Anschliesend fand ein Vergleich zwischen klinischem, endosonographischem und intraoperativem Befund statt. Laut klinischer Untersuchung hatten 32 von 47 Patienten ein Abszess- und Fistelleiden, zehn eine Analfissur und funf einen Tumor im analen Kanal. Mittels des endoanalen Ultraschalls mit der 7-mm-Sonde bestatigte sich bei 20 Patienten der Befund, bei 23 Patienten konnte die klinische Diagnose erweitert werden, und bei zwei Patienten lies sich bei sehr aboralem Befund kein endosonographisches Korrelat finden. Zwei Patienten wiesen intraoperativ einen von Klinik und Sonographie abweichenden Befund auf. Bezogen auf die Genauigkeit der Diagnose zeigten sich fur den 7-mm- und den 20-mm-Schallkopf eine Sensitivitat von 91,1% versus 29,6% und eine Richtigkeit von 91,5% versus 37,9%. Die „soft touch“-Sonographie mit der endoanalen 7-mm-Sonde erlaubt eine eindeutigere Zuordnung schallkopfnaher pathologischer Veranderungen und vervollstandigt somit die praoperative Diagnostik.

Ein 70-jahriger Patient stellte sich mit einer seit 6 Monaten bestehenden, ausgedehnten, grosenprogredienten perianalen Erosion vor. Daruber hinaus fanden sich einige kleinere Erosionen mit umgebender weislich retikularer Zeichnung am Penis. Die klinische Diagnose eines erosiven Lichen ruber wurde histologisch bestatigt. Nach Versagen mehrerer topischer Therapien und Absetzen des β-Blockers konnte der Befund durch 3 Zyklen einer Dexamethason-Pulstherapie (100 mg Dexamethason i.v. an 3 aufeinanderfolgenden Tagen in 4-wochigen Abstanden) zur langfristigen Abheilung gebracht werden.

Zusammenfassung Hintergrund: Bei ausgedehntem anogenitalen Warzenbefall werden nach den Leitlinien der Deutschen STD-Gesellschaft als mogliche Behandlungsformen mit vergleichbaren Rezidivraten die Kryotherapie, exzidierende Verfahren, die Elektrodesikkation, CO2- und Nd:YAG-Laserabtragung empfohlen. Bei diesen Verfahren besteht ein unterschiedlich hohes Risiko von Blutungen, Freisetzung potentiell infektionsfahiger Viruspartikel in die Raumluft, tiefer thermischer Destruktion, langer Wundheilungszeit und Vernarbung. Methode: Mit der Argon-Plasma-Koagulation werden anogenitale Warzen kontrolliert schichtweise abgetragen. Dabei wird Hochfrequenzstrom kontaktlos durch ionisiertes Argon auf die Gewebeoberflache ubertragen, wodurch eine oberflachliche Koagulation mit nahezu konstanter Eindringtiefe erreicht wird. Ergebnisse: Wir behandelten in der Zeit von Januar 2001 bis Marz 2003 54 Patienten mit ausgedehntem genitalen, analen oder kombinierten Befall von Warzen. Nach einmaliger Therapie waren 66 % der Patienten bis zum Abschlus der Kontrolluntersuchungen nach 4 Monaten erscheinungsfrei. Rezidive wurden bei 13 Patienten (24 %) nach 4 Wochen und bei weiteren 5 Patienten (9 %) zu einem spateren Zeitpunkt beobachtet. Nach weiteren Abtragungen sowie ggf. zusatzlicher Behandlung mit Imiquimod-Creme (n = 9, 17 %) waren alle Patienten erscheinungsfrei. Schlusfolgerung: Die Behandlung mittels Argon-Plasma-Koagulation stellt im Vergleich zu den anderen Verfahren eine besser kontrollierbare, risikoarme und rasch durchfuhrbare Methode der Behandlung anogenitaler Warzen dar. In Abhangigkeit vom Befallsmuster und individuellen Risikofaktoren erscheint im Einzelfall eine Nachbehandlung mit Imiquimod-Creme sinnvoll. Summary Background: According to guidelines of the German STD Association, appropriate treatment of extensive anogenital warts with comparable recurrence rates includes cryotherapy, surgical excision, electrosurgery, CO2- and Nd:YAG-laser vaporisation. All these procedures are associated with varying degrees of risk for bleeding, release of potentially infectious aerosol, deep thermal destruction, slow wound healing, and scarring. Methods: Using argon-plasma coagulation anogenital warts can be removed in layers in a controlled manner. High frequency current flows through the argon plasma to the tissue, allowing well-controlled, superficial tissue destruction. Results: From January 2001 to March 2003, 54 patients with extensive genital, anal or anogenital warts were treated. After one treatment, 66 % of the patients remained disease-free in the following 4 months. Thirteen patients (24 %) showed early recurrence after 4 weeks, five patients (9 %) at a later date. In these patients, further treatment, in 9 cases combined with topical imiquimod cream, were necessary for complete remission. Conclusion: Compared to other therapeutic procedures, argon-plasma coagulation is a better controlled, quick and low-risk option for the treatment of anogenital warts. Depending on the type of involvement and individual risk factors, postoperative treatment with topical imiquimod cream may be useful.

Imaging of the anorectal region has drastically changed over the past decade by the introduction of anal endosonography. This method has been used to localize injuries to the anal sphincters, fistula tracts and abscesses as well as to assess local invasion of cancerous lesions. It allows a quick and easy visualisation of the anorectal mucosa and the surrounding muscular structures. Limitations of endosonography include strictures and acute painful conditions. These caveats are largely caused by the size of regular rectal probes with an average diameter of 17 to 20 mm. We compared a new rectal probe with an external diameter of only 7 mm to a regular probe with 20 mm. From April 1999 to March 2000 80 patients with acute and chronic anal pain were examined. Even patients with acute anal pain could be examined without anaesthesia or sedation. The minimal compression and the absence of stretching artefacts of the 7 mm probe enabled us to depict the anal canal in an almost physiologic state. Marginal fistulas and haemorrhoidal knots in their anatomical localisation in the anal canal were easily identified. The introduction of endoanal ultrasound probes with a diameter below 1 cm represent a major improvement particularly for imaging all layers off the anal canal even under acute pain.

Management of patients with anorectal melanoma is still controversial. To reach a rationale therapeutic approach, we reviewed our experience obtained over the past decade. In all, 19 consecutive patients with the diagnosis of anorectal melanoma were included in this retrospective survey. Details of the patients' presentation, symptoms, tumour size and histology and tumour state were recorded, and the primary therapeutic procedures were evaluated in detail. The size of the tumours ranged between 0.5 and 7 cm in diameter. The median tumour thickness was 10 mm (range 0.6-40 mm). At diagnosis, six of 19 patients already presented with either regional or distant metastases. The remaining 13 patients were treated with curative intend, either by abdomino-perineal resection (APR) or wide local excision (WLE). The form of operative therapy, however, had no impact on overall survival. Nevertheless, the incidence of local recurrences was lower after APR even for patients with less favourable tumours. In conclusion, WLE alone is not sufficient for local tumour control of thick anorectal melanoma.

Schwannoma is usually a subcutaneous benign neoplasm that derives from nerve sheath. Pain and neurologic symptoms are uncommon, and exclusively dermal tumors are very rare. Solitary schwannoma has a traumatic origin in some cases, and rarely occur as a part of neurofibromatosis or schwannomatosis. An association of deeply located schwannoma with foreign material has been reported in very few cases. To our knowledge, we present the first case of a painful dermal schwannoma in association to foreign material.

Langerhans cell histiocytosis (LCH) mainly affects children and rarely occurs in adults [1]. Mostly, LCH presents as single system disease (SS) affecting only one organ system; in multisystem disease (MS), bone, skin, mucosae, lung, liver, spleen, bone marrow, lymph nodes, hypothalamus and the pituitary gland can be involved [1-3]. We report two patients with perianal skin ulcerations as the initial symptom of LCH. Both were successfully treated with intravenous vinblastine and oral prednisone, according [...]