Schulte Kw

Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial

BACKGROUND Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased survival compared with observation. METHODS In this multicentre, randomised, phase 3 trial, we enrolled patients with cutaneous melanoma of the torso, arms, or legs from 41 German skin cancer centres. Patients with positive sentinel lymph node biopsy results were eligible. Patients were randomly assigned (1:1) to undergo complete lymph node dissection or observation with permuted blocks of variable size and stratified by primary tumour thickness, ulceration of primary tumour, and intended adjuvant interferon therapy. Treatment assignment was not masked. The primary endpoint was distant metastasis-free survival and analysed by intention to treat. All patients in the intention-to-treat population of the complete lymph node dissection group were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02434107. Follow-up is ongoing, but the trial no longer recruiting patients. FINDINGS Between Jan 1, 2006, and Dec 1, 2014, 5547 patients were screened with sentinel lymph node biopsy and 1269 (23%) patients were positive for micrometastasis. Of these, 483 (39%) agreed to randomisation into the clinical trial; due to difficulties enrolling and a low event rate the trial closed early on Dec 1, 2014. 241 patients were randomly assigned to the observation group and 242 to the complete lymph node dissection group. Ten patients did not meet the inclusion criteria, so 233 patients were analysed in the observation group and 240 patients were analysed in the complete lymph node dissection group, as the intention-to-treat population. 311 (66%) patients (158 in the observation group and 153 in the dissection group) had sentinel lymph node metastases of 1 mm or less. Median follow-up was 35 months (IQR 20-54). Distant metastasis-free survival at 3 years was 77·0% (90% CI 71·9-82·1; 55 events) in the observation group and 74·9% (69·5-80·3; 54 events) in the complete lymph node dissection group. In the complete lymph node dissection group, grade 3 and 4 events occurred in 15 patients (6%) and 19 patients (8%) patients, respectively. Adverse events included lymph oedema (grade 3 in seven patients, grade 4 in 13 patients), lymph fistula (grade 3 in one patient, grade 4 in two patients), seroma (grade 3 in three patients, no grade 4), infection (grade 3 in three patients, no grade 4), and delayed wound healing (grade 3 in one patient, grade 4 in four patients); no serious adverse events were reported. INTERPRETATION Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller. FUNDING German Cancer Aid.

Ex vivo Application of δ‐Aminolevulinic Acid Induces High and Specific Porphyrin Levels in Human Skin Tumors: Possible Basis for Selective Photodynamic Therapy

Abstract— In photodynamic therapy with topically applied δ‐aminolevulinic acid porphyrins are acting as photosensitiz‐ers. The profile of porphyrin metabolites in normal or in neoplastic skin after administration of δ‐aminolevulinic acid has not been determined in detail yet. Thus, to study porphyrin biosynthesis in human skin an organ culture model was developed. Explant pieces of normal skin, ker‐atoacanthoma, and basal cell carcinoma were incubated with 1 niM δ‐aminolevulinic acid for 36 h. Levels of δ‐aminolevulinic acid, porphyrins and porphyrin metabolites were measured in tissues and supernatants. After incubation with δ‐aminolevulinic acid, higher porphyrin levels were demonstrated in tumors as compared to normal skin. In supernatants, most of formed porphyrins, preferentially highly carboxylated porphyrin metabolites, were measured. The pattern of synthesized porphyrins differed between normal and neoplastic skin explants. In tissues of basal cell carcinomas protoporphyrin was preferentially shown and tissues of keratoacanthomas were characterized by a predominance of coproporphyrin as compared to normal skin. The results show that explant cultures offer an easy approach to examine the porphyrin biosynthesis of various tissues. The tumor‐specific δ‐aminolevulinic acid metabolism indicates additional porphyrin metabolites such as coproporphyrin apart from protoporphyrin as effective photosensitizers and may offer a novel approach to tumor‐selective photodynamic damage.

Photodynamische Therapie und Mamillenplastik eines großflächigen Rumpfhautbasalioms der Mamma Effektive Kombinationstherapie unter photodynamischer Diagnostik

ZusammenfassungEs wird die Behandlung eines großflächigen Basalioms (ca. 10×6 cm) an der rechten Mamma einer 48jährigen Patientin dargestellt. Aufgrund der Histologie eines oberflächlichen Rumpfhautbasalioms entschlossen wir uns, den Tumor mit der photodynamischen Therapie (PDT) zu behandeln. Hierzu wurden δ-Aminolävulinsäure (δ-ALA, 20%) topisch aufgetragen und das Gewebe mit rotem Licht (570–750 nm; 180 J/cm2) bestrahlt. Die PDT wurde zweimal wiederholt. Hierdurch konnte klinisch eine nahezu vollständige Remission des Tumors erzielt werden. In der photodynamischen Diagnostik (PDD) zeigten sich aber noch deutlich einige persistierende, z.T. die Mamille infiltrierende Basaliominseln. Diese wurden durch Exzision entfernt und anschließend wurde der Defekt mittels einer Mamillenplastik verschlossen. Durch die Kombination der beiden Therapieformen konnte der großflächige Tumor mit einem ausgezeichneten kosmetischen Ergebnis behandelt werden. Die Falldarstellung soll zum einen die Grenzen der topischen PDT, zum anderen die Effizienz der PDD bei gezieltem Einsatz darstellen.SummaryWe treated a large superficial basal cell carcinoma (ca. 10×6 cm) on the right breast in a 48-year old woman with photodynamic terapy (PDT). Fractionated PDT was performed by topical application of δ-aminolevulinic acid (δ-ALA, 20%) with subsequent red light (570–750 nm; 180 J/cm2) in three sessions. Nearly total remission of the tumor resulted; however, a few residual neoplastic islands partly infiltrating the nipple-areola complex could be detected by photodynamic diagnosis (PDD). These fluorescent areas were marked, excised, and the defect was closed by a rotation advancement flap. Total excision of the tumor was verified histologically. By combining PDT and surgery, this large tumor was treated with excellent cosmetic results. This case demonstrates the efficiency of topical PDT with adjunctive plastic surgery controlled by PDD even in large tumors.

Pilomatricoma in Elderly Individuals

We report on 4 elderly patients aged 54–85 years with histopathologically diagnosed pilomatricoma who had been seen in our department from 1993 to 1997. Pilomatricoma is a rather uncommon neoplasm in middle-aged and old patients. It is much better known in children. Here, we clinically studied these 4 cases of pilomatricoma in elderly patients (above 50 years of age) to show the variety of clinical differential diagnosis and discuss the clinicopathological features. The results of the present study indicate that the differential diagnosis of pilomatricoma should also be considered in elderly individuals.

Eccrine Porocarcinoma of the Head: An Important Differential Diagnosis in the Elderly Patient

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications.

Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial.

LBA9002 Background: Complete lymph node dissection (CLND) following positive sentinel node biopsy (SLNB) was evaluated in a randomized phase III trial. METHODS 1,258 patients with cutaneous melanoma of the trunk and extremities and with positive SLNB were evaluated. Of these, 483 (39%) agreed to randomization into the clinical trial. 241 patients underwent observation only, 242 received CLND. Both groups had a subsequent 3-years follow-up. Recurrence-free (RFS), distant metastases free (DMFS) and melanoma specific (MSS) survival were analyzed as endpoints. RESULTS Patient enrolment was performedfrom January 2006 to December 2014. In the intent to treat analysis, both groups did not differ significantly in distribution of age, gender, localization, ulceration, tumor thickness (median 2,4 mm in both groups), number of positive nodes, or tumor burden in the SN. The mean follow-up time was 34 months (SD ± 22.1). No significant treatment-related difference was seen in the 5-years RFS (P = 0.72), DMFS (P= 0 .76) and MSS (P = 0.86) in the overall study population. CONCLUSIONS In this early analysis of trial results, no survival benefit was achieved by CLND in melanoma patients with positive SLNB. A subsequent analysis three years after inclusion of the last patient is planned.

Cylindroma of head and neck: review of the literature and report of two rare cases.

Cylindromas are very rare and benign adnexal tumours of the skin. Very few reports of these benign tumours are reported in the literature. Dermal cylindromas are characterised as a benign neoplasm of the eccrine sweat glands. The most frequent location is the head and neck. Multiple occurrences are often linked to the Brooke-Spiegler syndrome. The Brooke-Spiegler syndrome is inherited as an irregular autosomal dominant trait. A malignant transformation to an adenoid cystic carcinoma is also described in the literature. The leading treatment modality described in the literature is the complete surgical removal of the lesions. Here, a systematic review of the literature is presented with two rare cases of cylindromas.

Cutaneous side effects of hydroxyurea treatment for polycythemia vera

A 68-year-old women with polycythemia vera was treated with hydroxyurea for 8 years and developed painful ulcers on her lower legs, multiple hypertrophic actinic keratoses and a squamous cell carcinoma. After discontinuing hydroxyurea therapy the leg ulcers resolved within 8 weeks. The hypertrophic actinic keratoses and squamous cell carcinoma were treated with cryotherapy and excision, respectively. Hydroxyurea induces a variety of cutaneous side effects such as painful leg ulcers and squamous cell carcinomas. Given the wide variety of adverse cutaneous side effects associated with long-term hydroxyurea therapy, the first step in management is to insure that physicians and patients are aware of the specific risks of this treatment. Patients under hydroxyurea therapy should be monitored closely by dermatologists to early detect and treat the cutaneous side effects.

Besondere Notfälle in der Dermatologie

ZusammenfassungBei Notfällen in der Dermatologie handelt es sich um ein weites Spektrum von Erkrankungen, die eine umgehende stationäre oder auch intensivmedizinische Versorgung erfordern. Eine schnelle Diagnosestellung und umgehende Einleitung einer adäquaten Therapie sind notwendig, da einige dieser dermatologischen Erkrankungen mit einer hohen Mortalität oder mit schwerwiegenden Dauerschäden assoziiert sein können. Klassische Beispiele für dermatologische Notfälle sind: die bakteriellen Infektionen Waterhouse-Friderichsen-Syndrom, das staphylokokken- und streptokokkenbedingte toxische Schocksyndrom, die nekrotisierende Fasziitis und das nekrotisierende Erysipel. Einen weiteren besonderen Notfall stellen die Giftschlangenbisse dar.AbstractEmergency cases in dermatology are rare but potentially life-threatening conditions. They comprise a broad spectrum of diseases which require immediate hospitalization or even intensive care. A rapid diagnosis and appropriate therapy is necessary since some of these emergency cases are associated with a high mortality and with severe disabling complications. Typical examples are: the bacterial infections Waterhouse-Friderichsen syndrome, necrotizing erysipelas and necrotizing fasciitis, as well as staphylococcal and streptococcal toxic shock syndromes. Another special emergency situation is venomous snake bites.

Kutane Nebenwirkungen einer Hydroxyurea-Therapie bei Polycythaemia vera

A 68-year-old women with polycythemia vera was treated with hydroxyurea for 8 years and developed painful ulcers on her lower legs, multiple hypertrophic actinic keratoses and a squamous cell carcinoma. After discontinuing hydroxyurea therapy the leg ulcers resolved within 8 weeks. The hypertrophic actinic keratoses and squamous cell carcinoma were treated with cryotherapy and excision, respectively. Hydroxyurea induces a variety of cutaneous side effects such as painful leg ulcers and squamous cell carcinomas. Given the wide variety of adverse cutaneous side effects associated with long-term hydroxyurea therapy, the first step in management is to insure that physicians and patients are aware of the specific risks of this treatment. Patients under hydroxyurea therapy should be monitored closely by dermatologists to early detect and treat the cutaneous side effects.