Stephan Lischner

Prospective Randomized Trial of Interferon Alfa-2b and Interleukin-2 as Adjuvant Treatment for Resected Intermediate- and High-Risk Primary Melanoma Without Clinically Detectable Node Metastasis

PURPOSE Low-dose interferon alfa (IFNalpha) has been shown to have limited effects in the adjuvant treatment of patients with intermediate- and high-risk primary melanoma. We hypothesized that a combination regimen with low-dose interleukin-2 (IL-2) may improve survival prospects in these patients. PATIENTS AND METHODS After wide excision of primary melanoma without clinically detectable lymph node metastasis (pT3 to 4, cN0, M0), 225 patients from 10 participating centers were randomly assigned to receive either subcutaneous low-dose IFNalpha2b (3 million international units [MU]/m2/d, days 1 to 7, week 1; three times weekly, weeks 3 to 6, repeated all 6 weeks) plus IL-2 (9 MU/m2/d, days 1 to 4, week 2 of each cycle) for 48 weeks, or observation alone. The primary end point was prolongation of a relapse-free interval. RESULTS Of the 225 enrolled patients, 223 were found to be eligible. Median follow-up time was 79 months. All evaluated prognostic factors were well balanced between the two arms of the study. Relapses were noticed in 36 of 113 patients treated with IFNalpha2b plus IL-2 and in 34 of 110 patients with observation alone. Five-year disease-free survival of those who had routine surgery supplemented by IFNalpha2b and IL-2 treatment was 70.1% (95% confidence interval [CI], 61.3% to 78.9%), compared with 69.9% in those receiving surgery and observation alone (95% CI, 60.7% to 79.1%) in the intention-to-treat analysis. Evaluation of the overall survival did not show any difference between treated and untreated melanoma patients (P =.93). CONCLUSION Adjuvant treatment of intermediate- and high-risk melanoma patients with low-dose IFNalpha2b and IL-2 is safe and well tolerated by most patients, but it does not improve disease-free or overall survival.

Complete remission of a radio-resistant cutaneous angiosarcoma of the scalp by systemic treatment with liposomal doxorubicin

Summary We report an 80‐year‐old man suffering from an angiosarcoma of the scalp. Because of the wide extent of the lesions, surgery was not performed. Instead, the patient was treated with electron‐beam radiation. Later, the patient failed to benefit from radiotherapy demonstrated by a local relapse and new malignant lesions. Additionally, a cervical lymph node metastasis appeared for the first time. Subsequently, we successfully administered liposomal doxorubicin (Caelyx®). Shortly after administration of two cycles the scalp angiosarcoma showed a clear regression. Following six cycles, the patient clinically showed a complete remission of all skin lesions and the cervical lymph node; metastasis was confirmed by histology and fine needle aspiration, respectively. Liposomal and pegylated doxorubicin, a cytostatic drug belonging to the anthracyclines, has already shown to be effective and mostly well tolerated in the therapy of acquired immune deficiency syndrome‐related Kaposis sarcoma and very recently in cutaneous T‐cell lymphoma, too. Caelyx® appears to be a promising alternative to conventional treatment of cutaneous angiosarcoma.

Photodynamic therapy for skin rejuvenation: treatment options – results of a consensus conference of an expert group for aesthetic photodynamic therapy

In addition to providing effective treatment for non‐melanoma skin cancers or their precursors, photodynamic therapy (PDT) has also attracted considerable attention for its use on aesthetic dermatology. In a first consensus publication the mechanisms of action of its photorejuvenation effects and recent studies were presented; in this paper treatment protocols for the different anatomical regions exposed to chronic sun damage like face, neck, décolleté and the back of the hands are given and suitable procedures for pre‐ and after‐care are discussed.

Sicherheitsabstände bei der Exzision des primären malignen Melanoms Diskussionsvorschläge aufgrund von Ergebnissen aus kontrollierten klinischen Studien

ZusammenfassungDie vollständige Exzision des malignen Melanoms stellt die Therapie der ersten Wahl bei Primärtumoren dar. Inzisionsbiopsien bleiben seltenen Indikationen vorbehalten. Die Wahl des geeigneten Sicherheitsabstandes um den Primärtumor war fast 70 Jahre lang von anekdotischen Fallberichten und Dogmen geprägt, die erst durch Ergebnisse kontrollierter klinischer (prospektiv-randomisierter) Studien revoziert wurden. Nach den Ergebnissen sorgfältig durchgeführter, größerer Untersuchungen darf heute davon ausgegangen werden, dass geringere Sicherheitsabstände weder die Rate von Satelliten- noch von In-Transit-Metastasen erhöhen oder die Metastasierungsfrequenz statistisch signifikant beeinflussen. Satelliten- und In-Transit-Metastasen werden in Abhängigkeit vom maximalen vertikalen Tumordurchmesser des Melanoms selten (ca. 0,1%) bei dünnen Melanomen, häufiger (ca. 10%) bei dickeren Melanomen (>4 mm) beobachtet. Die Analyse der Gesamtüberlebenszeiten aller randomisierten Studien weist keine Prognoseverschlechterung durch einen geringeren Sicherheitsabstand bei der operativen Primärtumorentfernung auf. Basierend auf diesen Ergebnissen, wäre eine In-toto-Exzision von In-situ-Melanomen, ein Sicherheitsabstand von 1 cm für dünne Melanome (<1 mm Tumordicke) sowie 1–2 cm für dickere Melanome (>1 mm Tumordicke) zu empfehlen. Durch diese Vorgehensweise werden in nahezu allen Fällen primäre Defektverschlüsse ermöglicht sowie die Morbidität und Kosten der operativen Behandlung gesenkt. Wir möchten die vorliegende Arbeit als Diskussionsgrundlage vor einer nötigen Überarbeitung der derzeit gültigen DDG-Richtlinien zur operativen Primärversorgung von Melanompatienten verstanden wissen.AbstractExcisional biopsy is recommended as the procedure of choice whenever there is suspicion of malignant melanoma. Incisional biopsies are only rarely indicated. For nearly seventy years the debate about the optimum resection safety margin around the primary tumor was influenced by historical case reports and paradigms. Recently, controlled clinical studies have provided new insights. Accumulating evidence over the last two decades shows that narrower surgical margins influence neither the rate of satellites or in-transit-metastases nor the occurrence of advanced metastatic disease. Local recurrence is rare (approx. 0.1%) when primary tumors are thin and is seen more often (approx. 10%) in primary tumors of greater thickness (> 4 mm). Analysis of the overall survival in randomized trials shows equal prognosis for malignant melanoma for narrow and wide resection margins. Due to these findings in-toto excisional biopsy for in-situ melanoma, a resection margin of 1 cm for thin primary tumors (<1 cm tumor thickness) and a resection margin of 1 to 2 cm for primary tumors greater than 1 mm appears sufficient. With these recommendations, primary closure of wounds will be possible in nearly all cases, reducing surgical costs and morbidity. This article should serve as a basis of discussion for the proposed revision of the current guidelines of the German Dermatologic Society (DDG) on the primary surgical care of melanoma patients.

Photodynamic therapy for skin rejuvenation: review and summary of the literature – results of a consensus conference of an expert group for aesthetic photodynamic therapy

Skin rejuvenating effects of photodynamic therapy (PDT) for photoaged skin has been well‐documented in several clinical trials. Different photosensitizers (5‐aminolevulinic acid, methyl aminolevulinate) and diverse light sources (light‐emitting diodes, lasers, intense pulsed light) have been used with promising results. An improvement of lentigines, skin roughness, fine lines and sallow complexion has been achieved with PDT. These clinically evident effects are at least in part due to histologically proven increase of collagen and decrease of elastotic material in the dermis. Effective improvement of photoaged skin, simultaneous treatment and possibly also prevention of actinic keratoses, the possibility of repeated treatments and, in contrast to other procedures, limited and calculable side effects make PDT a promising procedure for skin rejuvenation.

Diagnostic and therapeutic procedures for management of melanoma during pregnancy: risks for the fetus?

In the treatment of malignant melanoma, various stage‐dependent diagnostic and therapeutic procedures are widely accepted.The situation becomes more complicated in pregnant women due to potential hazardous side effects to the fetus. We report on a 36‐year‐old woman, who was admitted with a high‐risk malignant melanoma on the right cheek. Prior to surgery we performed computed tomography (CT)‐scans that were unremarkable with the exception of “two small cysts of the uterus” The primary melanoma was excised and a sentinel node biopsy was performed under general anesthesia using radioactive tracers. Afterwards, adjuvant therapy with interferon alpha 2b was initiated. Five weeks later our patient reported that she was pregnant with twins in their eleventh week of gestation, although she previously denied several questions regarding a potential pregnancy. She declined the offer of an abortion and elected to continue with the interferon treatment against our medical advice. In the 36th week of gestation, she developed regional lymph node metastases. Consequently, labor was induced, resulting in the delivery of healthy twins. Six months later our patient developed lung metastases. Despite several chemotherapy regimens, she died one year later. An interdisciplinary approach to obtaining informed consent and managing female high risk melanoma patients with potential or present pregnancy is presented.

Surgical Standards in the Primary Care of Melanoma Patients

Excisional biopsy is recommended as the procedure of choice whenever there is suspicion of malignant melanoma. There are only few indications for incisional biopsies, which – in contrast to former opinions – do not worsen the prognosis. For nearly 70 years the debate about the optimal resection safety margin around the primary tumor was influenced by historical case reports and paradigms. Recently, controlled clinical studies provided new insights. Accumulating evidence over the past two decades showed that narrower surgical margins do not have any influence on the rate of advanced metastatic disease. Local recurrence is rare (approximately 0.1%) when primary tumors are thin and is seen more often (approximately 10%) in primary tumors of greater thickness (>4 mm). Analysis of the overall survival in randomized trials shows equal prognosis for malignant melanoma for narrow and wide resection margins. Due to these findings in-toto excisional biopsy for in-situ melanoma, a resection margin of 1 cm for primary tumors with a tumor thickness up to 2 mm and a resection margin of 2 cm for primary tumors greater than 2 mm appears sufficient. By this procedure primary closure of wounds will be possible in nearly all cases, morbidity and costs of surgical approaches will be reduced. For a long time it has been discussed whether prophylactic removal of lymph nodes (‘elective lymph node dissection’) is of benefit for melanoma patients. More recently ‘selective’ lymphadenectomy (‘sentinel node biopsy’, SNB) has been proposed to evaluate the status of the first draining lymph node (‘sentinel node’) of the regional basin. Several studies now demonstrate that the sentinel node evaluation for underlying metastatic disease reflects the status of the entire lymph node region and is therefore a useful prognostic factor superior to measurement of tumor thickness in primary melanoma. However, it is unclear whether sentinel node biopsy is of benefit for a better survival in affected patients.

Temozolomid als Therapieoption bei Patienten mit fernmetastasiertem Melanom und ungünstiger Prognose

ZusammenfassungHintergrund und Fragestellung. Melanompatienten mit weit fortgeschrittener Fernmetastasierung nach erfolglosen Therapieversuchen werden üblicherweise von klinischen Studien ausgeschlossen. Wir berichten über die Verwendung von Temozolomid (Temodal®) als einem oral verfügbaren und liquorgängigen Zytostatikum bei 25 Melanompatienten mit Fernmetastasierung. Patienten/Methodik. Es wurden 25 Patienten (17 Frauen, 8 Männer) im Alter von 24–82 Jahren (Mittelwert: 55,5 Jahre), von denen 19 im Stadium der Fernmetastasierung mindestens eine und bis zu 4 Vortherapien erhalten hatten, in diese retrospektive Untersuchung einbezogen. Elf Patienten (44%) zeigten eine zerebrale Metastasierung vor Therapiebeginn. Es wurden 200 mg/m2 Körperoberfläche Temozolomid per os verabreicht. Die orale häusliche Applikation erfolgte an Tag 1–5 der 1. Woche und wurde in der 5. Woche wiederholt. Ergebnisse. Von den 23 auswertbaren Patienten zeigten 2 (8,7%) eine partielle Remission, 2 (8,7%) eine “minor response”, 6 (26,1%) eine Stabilisierung der Erkrankung, bei einem Patienten (4,3%) wurde eine “mixed response” erzielt, und 12 (52,1%) litten an einer Progredienz der Metastasen. Es wurden Remissionen von Hirn-, Lungen-, Leber-, Lymphknoten- und Muskelfiliae beobachtet. Zwei Patienten brachen die Therapie aufgrund von Leuko- und Thrombozytopenie (WHO-Grad 3 und 4) ab. Bei allen anderen Patienten konnte die Therapie – wie geplant – ohne Dosisreduktion bei guter Verträglichkeit verabreicht werden. Der Medianwert der Überlebenszeit beträgt 7 Monate (2–28+ Monate) seit Therapiebeginn und 15 Monate (4–63+ Monate) seit Beginn der Fernmetastasierung. Schlussfolgerung. Temozolomid stellt eine patientenfreundliche Therapieoption beim fernmetastasierten Melanom mit ungünstiger Prognose dar.AbstractBackground and objective. Stage IV melanoma patients with a very advanced disease are usually excluded from clinical trials. We treated 25 stage IV patients with temozolomide – a cytostatic drug with 100% oral bioavailability and considerable penetration of CNS tissue. Patients/Methods. 25 patients (17 female, 8 male) between 24 and 82 years (mean: 55.5 years) were included in this retrospective study. 19 patients had received at least one and up to four previous chemotherapy regimens during the course of stage IV disease. 11 (44%) patients showed cerebral metastases prior to therapy with temozolomide. 200 mg/m2 temozolomide were given orally at home on day 1 to 5 in week 1 and in week 5, respectively. Results. Out of 23 evaluable patients 2 (8.7%) showed a partial remission, 2 (8,7%) a minor response, 6 (26.1%) had stable disease, 1 (4,3%) a mixed response, and 12 (52.1%) patients experienced disease progression. Sites of remission included brain, lung, liver, lymph nodes and muscle. Two patients interrupted therapy due to severe leuko- and thrombocytopenia (WHO grade 3 and 4). All other patients tolerated treatment with temozolomide well and no dose reduction was necessary. The median overall survival was 7 months (2–28+ months) since beginning of therapy and 15 months (4–63+ months) since onset of stage IV disease. Conclusion. Temozolomide represents a safe treatment option in patients with metastatic melanoma and poor prognosis.

Photodynamische Therapie zur Hautverjüngung: Übersicht und publizierte Datenlage – Ergebnisse einer Konsensus‐Konferenz des Arbeitskreises Ästhetische Photodynamische Therapie

Die hautverjungende Wirkung der photodynamischen Therapie (PDT) lichtgealterter Haut ist mittlerweile durch zahlreiche klinische Studien gut dokumentiert. Verschiedene Photosensibilisatoren (5-Aminolavulinsaure, Aminolavulinsauremethylester) und unterschiedliche Beleuchtungsquellen (Lichtdioden, Laser, Blitzlampen) wurden mit meist gutem Erfolg in den Studien eingesetzt. Eine Verbesserung von Lentigines, Hautrauigkeit, feinen Falten und Hautkolorit konnte durch die PDT erzielt werden. Diese klinisch sichtbaren Effekte beruhen unter anderem auf einer histologisch nachgewiesenen Abnahme des elastotischen Materials in der Dermis und einer subepidermalen Neusynthese von Kollagen. Die effektive Verbesserung lichtgealterter Haut, die gleichzeitige Behandlung und moglicherweise auch Pravention von aktinischen Keratosen, die Moglichkeit wiederholter Behandlungssitzungen sowie im Gegensatz zu anderen Verfahren limitierte und gut kalkulierbare Nebenwirkungen machen die PDT zu einem vielversprechenden Verfahren zur Hautverjungung.

Das Lipom der Lippe Eine seltene Differenzialdiagnose

ZusammenfassungWir berichten über eine 49-jährige Frau mit einem seit 15 Jahren bestehenden ca. kirschgroßen Tumor im Bereich der Unterlippe. Dieser Tumor hatte stetig an Größe zugenommen und führte zu einer starken psychischen Beeinträchtigung der Patientin. Zusätzlich erschwerte er aufgrund seiner Größe die Nahrungsaufnahme. Wir exstirpierten den Tumor in Lokalanästhesie, die histologische Aufarbeitung ergab ein Lipom. Lipome im Bereich der Lippe wurden bisher in der deutschsprachigen Literatur nicht beschrieben. Auch weltweit liegen nur wenige Fallberichte vor.AbstractWe report on a 49 year-old female patient with a cherry-sized tumor of the lower lip, which over several years had steadily increased in size. The patient was psychologically affected by the appearance of the tumor and had difficulties to eat. We excised the tumor in local anaesthesia. Histology confirmed the clinical suspicion of lipoma. A total of four lipomas at this location have been reported world-wide.