Preventive health examinations: protocol for a prospective cross-sectional study of German employees aged 45 to 59 years (Ü45-check).

Objective: Early identification of health-related risk factors is of great importance for maintaining workability. Screening examinations can help to detect diseases at an early stage and provide more needs-based recommendations. This study aims (1) to assess the individual need for prevention or rehabilitation based on preventive health examinations compared to a questionnaire survey, (2) to assess the results of the preventive health examinations compared to the Risk Index - Disability Pension (RI-DP), (3) to assess the results of the questionnaire survey compared to the RI-DP, (4) to assess the general health status of the sample (target population > 1,000) in German employees aged 45-59, (5) to identify the most common medical conditions. A further study question aims, and (6) to investigate the general health status of the specific occupational groups. Methods: Comprehensive diagnostics including medical examination, anamnesis, anthropometric measurements, bioelectrical impedance analysis (BIA), handgrip strength, resting electrocardiogram (ECG), resting blood pressure, pulse wave velocity (PWV), and laboratory blood analyses added by a questionnaire are conducted. The research questions are analyzed in an exploratory manner. Results and conclusion: We expect that the results will allow us to formulate recommendations regarding screening for prevention and rehabilitation needs on a more evidence-based level.Clinical Trial Registration: DRKS ID: DRKS00030982.

Role of IL-17 in atopy-A systematic review.

PURPOSE OF REVIEW: Atopy is defined as the genetic predisposition to react with type I allergic diseases such as food-, skin-, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL-17A (IL-17) is mainly produced by Th17 cells and belongs to the IL-17 family of cytokines, IL-17A to F. While IL-17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL-17 in allergic diseases. The present study aimed to elaborate specifically the role of IL-17 in atopy. METHODS: A systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL-17 and atopy/allergic diseases. RESULTS: In total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL-17 pathway has been investigated. Serum IL-17 was elevated in all allergic diseases. In AR, serum and nasal IL-17 levels correlated with the severity of the disease. In food allergies, serum IL-17E was also elevated in children. In AD, there is a trend for higher IL-17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL-17 levels were increased. In two studies, higher serum IL-17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL-17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post-bronchodilator) high reversibility. SUMMARY: The role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL-17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL-17 is elevated more often in acute and severe forms of allergic diseases.

A prospective, multi-centre, follow-up clinical study evaluating the safety and effectiveness of a 24mg/ml sodium hyaluronate soft tissue filler.

Highly concentrated hyaluronic acid dermal fillers commonly contain 20 mg/ml sodium hyaluronate. The soft tissue filler SF 24 contains 24 mg/ml sodium hyaluronate. It is a viscoelastic gel, which is moderately cross-linked and specifically designed to correct moderate to deep wrinkles and folds of facial skin.To evaluate the long-term safety and effectiveness of the SF 24 for facial augmentation.The primary endpoints were effectiveness and safety, which were measured by investigators' assessment of wrinkle/ fold/ defect severity and reaction severity, respectively. The Global Esthetic Improvement Scale (GAIS) evaluated secondary endpoints, such as patient and physician satisfaction. Data collection occurred at treatment date (day 0) and at each visit set at an interval of 21 days, 121 days, 213 days, and 395 days. A total of 74 individuals (3 male and 71 female) received treatment with SF 24 across five sites. The baseline value (2. 70) of wrinkle and fold severity was reduced to 1.22 directly after treatment and remained improved even after 273 days at 1.59. The improvements compared to baseline were all significant (p < .001). The injection-related reactions were mainly short-term (1-7 days), mild to moderate in severity, and resolved without intervention. SF 24 is safe and effective for facial volume augmentation. It shows long-lasting (9 months) results in treated patients.

Nonprescription acne vulgaris treatments: Their role in our treatment armamentarium-An international panel discussion.

BACKGROUND: Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. OBJECTIVES: This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. METHODS: The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. RESULTS: All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. CONCLUSION: The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Wound Healing Process After Thermomechanical Skin Ablation.

BACKGROUND AND OBJECTIVES: Energy-based devices have been widely applied for skin ablation. A novel ablation technique based on thermomechanical principles (Tixel© ) has been recently developed. The aim of this study was to examine the wound-healing process and clinical aspects after thermomechanical skin ablation. STUDY DESIGN/MATERIALS AND METHODS: Six female participants were treated with Tixel© on healthy skin of the dorsal side of the right forearm in a single session with a 600 µm protrusion and 12 milliseconds pulse. The treated area was examined with confocal laser scanning microscopy on day 1, 2, 7, and 14 after treatment. Clinical symptoms were evaluated at the same time-points. RESULTS: All patients developed erythema and mild edema on the treated areas, which completely disappeared within 14 days. No post-inflammatory hyperpigmentation or scarring was observed. Thermomechanical skin ablation resulted in the formation of homogeneous micro-ablation zones. Two weeks after ablation, the honeycomb patterns of the epidermis in all examined layers was thoroughly restored. Thus, wound-healing was completed. CONCLUSIONS: Wound healing after thermomechanical skin ablation is much faster compared with other fractionated ablation methods. Treatment intervals of 2-4 weeks could be recommended. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

MI (2-methyl-4-isothiazolin-3-one) contained in detergents is not detectable in machine washed textiles.

BACKGROUND: European legislation has banned the preservative methylisothiazolinone (MI) from inclusion in leave-on cosmetics. However, the risk for allergic reactions depends on exposure. The aim of this study was to determine the risk of MI in laundry detergents for household machine washing. METHODS: Different formulations of laundry detergents with commercial MI levels, up to one thousand ppm were used and three different types of clothes were washed in a normal household machine setting one time and 10 times. The level of MI was measured by HPLC. RESULTS: While MI could be retrieved in the positive control of clothes drenched with washing powder but not washed afterwards, MI could not be detected in any specimen of clothes washed under household conditions. The detection limit was 0.5 ppm. CONCLUSION: It is important to discuss the difference of risk and hazard. While MI clearly is a high hazard as a strong contact allergen, the risk depends on exposure. Regarding the risk of exposure levels for the consumer to MI in clothes it can be stated that the use of MI in laundry detergents is safe for the consumer if these products are used according to the instructions in the normal household setting machine wash.

A case report of combination treatment with potassium-titanyl phosphate laser and brimonidine topical gel in erythematotelangiectatic rosacea.

Laser therapies have been shown to provide symptom improvement in patients with erythema and telangiectasia of rosacea; however, they are associated with side effects such as erythema. Combinatorial treatment with pharmacological agents and laser have demonstrated better efficacy, fewer side effects and continued long-term remission compared with monotherapies. A case of moderate facial erythema that responded well to combination treatment with brimonidine 3 mg/g gel and a treatment course of potassium-titanyl phosphate (KTP) laser therapy is presented, showing a reduction from baseline, maintained after final laser session, by applying brimonidine 3 mg/g gel daily. Using brimonidine 3 mg/g gel to target post-laser treatment erythema is highly effective in minimising refractory erythema. Continued use of brimonidine 3 mg/g gel provides a sustained reduction of erythema, increasing the visibility of other signs and symptoms of rosacea that may be present. This can facilitate the treatment of these additional signs and symptoms.

Physikalische Methoden zur Behandlung der Rosazea.

Die Rosazea ist durch vielfältige vaskuläre Veränderungen gekennzeichnet. Neben Teleangiektasien und Erythemen treten häufig auch sogenannte "Flushings" auf. Haupteinsatzgebiete von Licht- und Lasersystemen sind diese vaskulären Veränderungen, wie Erytheme und Teleangiektasien. Neben dem KTP-Laser, dem Farbstofflaser (PDL) und dem Nd:YAG-Laser kommen auch Blitzlampen (IPL) zum Einsatz. Neben der Rückbildung der vaskulären Komponente, ist auch eine Verbesserung der papulopustulösen Komponente beschrieben. Während der KTP-Laser sehr gute Ergebnisse bei Teleangiektasien zeigt, werden der Farbstofflaser und die Blitzlampen bevorzugt bei flächigen Erythemen eingesetzt. Der ND:YAG-Laser kann bei Teleangiektasien und Erythemen eingesetzt werden, birgt aber von allen Systemen das nicht einschätzbare Narbenbildungsrisiko in sich. Die Bildung von Phymen stellt eine klinische Ausprägung der Rosazea dar. Das am häufigsten vorkommende ist das Rhinophym. Bei moderaten und schweren Formen steht die Abtragung im Vordergrund. Die klassische chirurgische Abtragung stellt eine Möglichkeit zur Behandlung dar, häufig kommt es hierbei jedoch intraoperativ zu stärkeren Blutungen. Alternativmethode ist die Elektrochirurgie und die Dermabrasion, wobei bei beiden Methoden Narbenbildungen auftreten können. Neuere Methoden wie die CO2 -Laserabtragung, eventuell in Kombination mit der Erbium:YAG-Abtragung, stellen sichere und komplikationsärmere Varianten dar.

Physical modalities for the treatment of rosacea.

Rosacea is characterised by a wide variety of vascular changes. Apart from telangiectasia and erythema, often so-called flushing occurs. These vascular abnormalities can be targeted with specific light and laser devices. In addition to KTP laser, pulsed dye laser (PDL) and Nd:YAG laser, also intense pulsed light devices (IPLs) are used. The described therapeutic effects include the reduction of vascular abnormalities and even improvement of papulopustular changes. While the KTP laser shows very good results in telangiectasia, the dye laser and IPL devices are used preferably in erythema. The Nd:YAG laser is also a possibility for patients with telangiectasia and erythema. However, compared to the other laser and light devices the Nd:YAG laser carries the highest risk of unpredictable scarring. Phymatous changes are another clinical manifestation of rosacea, mostly affecting the nose (rhinophyma). Moderate and severe cases are commonly treated with ablation modalities. Traditional surgery is a treatment option, but is often associated with major intraoperative bleeding. Alternative methods include electrosurgery and dermabrasion, although both methods can cause scarring. Newer methods such as CO2 laser ablation, possibly in combination with the erbium:YAG laser, are safe alternatives with a lower risk of complications.

A novel thermo-mechanical system enhanced transdermal delivery of hydrophilic active agents by fractional ablation.

The Tixel is a novel device based on a thermo-mechanical ablation technology that combines a sophisticated motion and a temperature control. The fractional technology is used to transfer a very precise thermal energy to the skin thereby creating an array of microchannels, accompanying by no signs of pain or inconvenience. This study aimed to evaluate the effect of the Tixel on the skin permeability of three hydrophilic molecular models: verapamil hydrochloride, diclofenac sodium, and magnesium ascorbyl phosphate. Tixel's gold-platted stainless steel tip heated to a temperature of 400°C was applied on skin for 8ms or 9ms at a protrusion of 400µm (the distance in which the tip protrudes beyond the distance gauge). The experiments were carried out partly in vivo in humans using a fluorescent dye and a confocal microscopy and partly in vitro using porcine skin and a Franz diffusion cell system. The results obtained in this study have shown that (a) no significant collateral damage to the skin tissue and no necrosis or dermal coagulation have been noted, (b) the microchannels remained open and endured for at least 6h, and (c) the skin permeability of hydrophilic molecules, which poorly penetrate the lipophilic stratum corneum barrier, was significantly enhanced by using Tixel's pretreatment.

A systematic review of the role of interleukin-17 and the interleukin-20 family in inflammatory allergic skin diseases.

PURPOSE OF REVIEW: Allergic skin diseases include atopic dermatitis/eczema, contact dermatitis, and drug hypersensitivity. Allergic skin diseases have a high prevalence. Atopic dermatitis is one of the most common inflammatory skin diseases and similar for allergic rhinitis and allergic asthma. Over a long period, allergic diseases have been regarded as immunoglobulin E-mediated T-helper-2 (Th2)-driven. But new cytokines and T cells have been discovered within the last years. In this systematic review, the focus is laid on interleukin-17 (IL-17) and the interleukin-20 (IL-20) family which appear to be fine-tuning the Th2-driven answer. RECENT FINDINGS: IL-17 is a proinflammatory cytokine, which is produced by T cells. Primarily, IL-17 is produced by activated CD4+ cells, called Th-17 cells. IL-17 regulates keratinocyte expression of adhesion molecules and chemokines. IL-17 is involved in the pathogenesis of inflammatory diseases as psoriasis, arthritis, and inflammatory bowel diseases. In allergic diseases, the involvement of the TH17/IL17-pathway has only been recently described. Regarding the IL-20 family, IL-22 is the most interesting and the most studied cytokine in terms of allergic inflammatory disorders. IL-22 is produced by T-helper 22 cells, a new subset of CD4+ cells. SUMMARY: IL-17 as well as IL-22 seem to play a role in the pathogenesis of allergic skin diseases.

Prospective evaluation of supportive care with or without CVD chemotherapy as a second-line treatment in advanced melanoma by patient's choice: a multicentre Dermatologic Cooperative Oncology Group trial.

This prospective, nonrandomized multicentre, phase III study compared best supportive care (BSC) alone with cisplatin, vindesine and dacabazine-based (CVD) chemotherapy and BSC in patients with advanced melanoma. A total of 117 pretreated patients with metastatic melanoma were evaluated, 34 patients in arm A (BSC) and 83 in arm B (BSC and CVD). Primary endpoint was overall survival and secondary endpoints were disease control rate and quality of life (European Organisation for Research and Treatment of Cancer QLQ-C30). Owing to sparse recruitment of patients for randomization, the protocol has been changed based on patients' choice. Baseline characteristics were imbalanced with respect to the Karnofsky Performance Index (P=0.001), the existence of brain metastases (P=0.035) and earlier application of chemoimmunotherapy (P=0.038). Disease control was observed in 8.8% of patients in arm A and in 28.9% of patients in arm B (P=0.028). Median overall survival time was 137 days in arm A and 229 days in arm B (P=0.014). Multivariate analyses could not ascribe this prognostic benefit to CVD treatment. No significant difference in the quality of life could be found. This study could not detect clear survival benefits for polychemotherapy with CVD compared with BSC alone in patients with advanced metastatic melanoma. Interestingly, having the choice of chemotherapy or BSC alone in a second-line situation, more than 70% of patients chose polychemotherapy.

Impact of lymph node metastases on serum level of melanoma inhibitory activity in stage III melanoma patients.

Melanoma patients in stage III have a considerable recurrence rate. The 10-year survival in this stage depends on the number and size of affected nodes. Currently, there is no optimal serum marker for early detection of relapse available. The goal of the study was to assess the utility of melanoma inhibitory activity (MIA) serum marker in the follow up and primary diagnosis of stage III melanoma patients. One hundred and thirty-eight melanoma patients in stage III at time of primary diagnosis were analyzed at time of primary diagnosis and during periodical routine follow up both for serum MIA using an enzyme-linked immunosorbent assay and for serum lactate dehydrogenase (LDH). Results were correlated with the positivity of the sentinel lymph node (SLN) and the number of lymph node metastases in the completion lymph node dissection at time of primary diagnosis. During follow up, the overall survival time was assessed using the Kaplan-Meier method in terms of elevated MIA (>12 ng/mL) values. Regarding SLN status, significant differences of MIA values (P = 0.024) and LDH (P = 0.007) were found, both within the normal cut-off. Having lymph node metastases in the completion lymph node dissection, significantly higher MIA values (12.55 ng/mL [±0.48], P < 0.0001) were found. In patients with three or more tumor-positive nodes, MIA values were significantly higher when compared to patients with one or two affected nodes (P = 0.024). In the routine follow-up, stage III patients with an MIA value of more than 12 ng/mL had a five times higher risk for developing recurrences (P < 0.0001). Patients with relapsing disease had a significantly (P < 0.0001) higher mean MIA value (13.76 ng/mL) compared to patients without relapse (7.52 ng/mL). The MIA serum marker can be helpful in patients undergoing lymph node dissection. Furthermore, during follow up, patients showing relapsing diseases can have an elevated MIA value.

Serum TNF-α, B2M and sIL-2R levels are biological correlates of outcome in adjuvant IFN-α2b treatment of patients with melanoma.

PURPOSE: There are no biological markers available to predict outcome in melanoma patients treated with adjuvant interferon-alpha (IFN-α). The clinical activity of IFN-α is thought to be mediated not only by anti-proliferative effects, but also by induction and modulation of secondary cytokines. We examined serum cytokine levels in IFN-α-treated patients to find potential biological markers for response or toxicity. PATIENTS AND METHODS: In a prospective randomized trial, 66 stages II and III melanoma patients underwent an induction treatment of 10 MU IFN α2b s.c. 5 ×/week, followed by either 5 MU or 10 MU IFN α2b s.c. 3 ×/week for a total of 2 years. Serial measurements of serum IL-1ß, IL-2, sIL-2R, IL-6, IL-10, TNF-α and ß-2 microglobulin (B2M) were taken. Two factorial analysis of repeated measurements (ANOVA) as well as univariate and multivariate analyses was used to identify prognostic factors for relapse and toxicity. RESULTS: TNF-α levels correlated with toxicity. In patients with relapse, significantly lower levels of TNF-α were detected at baseline and throughout therapy compared with patients without relapse. B2M and sIL-2R showed a significant increase throughout the therapy phase. At baseline, the combination of TNF-α, B2M and sIL-2R revealed a positive predictive value for relapse of 82.9% in the multivariate analyses. CONCLUSION: Low TNF-α levels are negatively associated with relapse-free survival. Conversely, high TNF-α levels are correlated with toxicity but seem to be beneficial to patients with regard to relapse-free survival. B2M and sIL-2R are biological markers of adjuvant IFN-α2b treatment.

Diagnostic value of melanoma inhibitory activity serum marker in the follow-up of patients with stage I or II cutaneous melanoma.

In the follow-up of melanoma patients, there is still a need for an optimal serum marker to discover recurrent disease at an early stage. Melanoma inhibitory activity (MIA) has been investigated as a serum marker for cutaneous melanomas. Although the prognosis for melanoma based on stage is generally good, the disease identified at later stages is associated with high levels of morbidity and mortality. The value of MIA testing in early-stage melanoma was the goal of this study. Five thousand three hundred and thirty-four MIA serum values from 1079 consecutive melanoma patients in stages I and II were obtained during routine follow-up at scheduled intervals. Sensitivity and specificity of MIA were calculated. The area under the receiver-operating characteristics curve and Somers' Dxy rank correlation were assessed. Metastasis occurred in 137 patients with a sensitivity of MIA testing of 67.6% in stage I and 65.6% in stage II patients. The specificity was 76.9% for stage I and 66.7% for stage II patients. The most reliable normal upper limit for MIA was redefined at 12.0 ng/ml, when compared with 8.8 and 15.0 ng/ml. Multivariate analysis revealed significantly more frequent false-positive values in elderly women and in men with an increased Breslow thickness.MIA adapted with a new cut-off level is then a useful serum marker even in the follow-up of not yet relapsed early-stage melanoma patients. In older women and in men with an increased tumor thickness, the higher rate of false-positive values should be considered before starting further diagnostics. Additional prospective studies to clarify the clinical combination with other serum markers seem promising.

Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma.

Synthetic oligodeoxynucleotides (ODNs), such as PF-3512676, that contain unmethylated cytosine-guanine motifs (CpG ODN) have been identified as highly potent immune activators by in vitro examinations and in murine models. CpG ODNs induce innate and adaptive immune responses by triggering Toll-like receptor 9 expressed by human B cells and plasmacytoid dendritic cells. A phase 1 study was initiated to investigate safety, tolerability, serum cytokine levels, cellular immune responses, and clinical activity of intralesional treatment with PF-3512676 in patients with basal cell carcinoma (BCC) or cutaneous or subcutaneous melanoma metastases. Intrapatient escalating doses of PF-3512676 (up to 10 mg) were injected intralesionally every 14 days in 5 patients with BCC and in cutaneous or subcutaneous metastases of 5 patients with melanoma. PF-3512676 was well tolerated. Local swelling and erythema occurred at the injection site in 9/10 patients. There was only 1 incidence of a grade III hematologic adverse event (lymphocytopenia). Local tumor regressions were observed in patients with BCC (1 complete regression, 4 partial regressions) and metastatic melanoma (1 complete regression). After treatment with PF-3512676, interleukin-6 was increased in all patients, interferon-gamma induced protein-10 in 8/10 patients, interleukin-12p40 in 7/10 patients, and tumor necrosis factor-alpha levels in 6/10 patients. All patients had biopsies; moderate to abundant cellular infiltrates of lymphocytes were found posttreatment in most lesions of both histologic types. Intralesional treatment of skin tumors with PF-3512676 was safe and well tolerated. Despite the relatively low dosage, clinical activity was demonstrated both in patients with BCC and with cutaneous or subcutaneous metastatic melanoma lesions.

High-dose platinum combination therapy in pretreated patients with disseminated melanoma.

BACKGROUND: There are no accepted second-line therapeutic options in patients with disseminated melanoma. We evaluated toxicity and efficacy of a combination therapy with cisplatin and carboplatin. METHODS: Fifty consecutively treated melanoma patients who were progressive after at least one previous chemotherapy received cisplatin 100 mg/m(2) intravenously and carboplatin 200 mg/m(2) intravenously in a 2-day regimen once every 28 days. RESULTS: As grade 3 and 4 toxicities, leucopenia (14%), thrombopenia (10%), anaemia (22%), nausea (8%), nephrotoxicity (4%), hypomagnesaemia (80%) and hepatotoxicity (2%) were observed. Among 42 patients evaluable for response, 2 (4.7%) had complete remission, 4 (9.5%) had partial remission and 21 (50%) had stable disease. The median progression-free time was 17 weeks (range 0-156) for all patients and 39 weeks (range 17-156) for patients with objective responses. The median overall survival time for all patients from the start of therapy was 32 weeks (range 2-156). Melanoma inhibitory activity levels of <12 ng/ml before therapy were identified to be associated with a favourable survival. CONCLUSION: Our results indicate that a combination of cisplatin and carboplatin in patients with pretreated disseminated melanoma has an acceptable safety profile, induces objective responses and may prolong survival.

Prognostic factors and impact of treatment in melanoma brain metastases: better prognosis for women?

BACKGROUND: Brain metastases are a common consequence in patients with stage IV melanoma associated with a grim prognosis. OBJECTIVE: The objective of this study was the examination of prognostic factors and the evaluation of different treatment options. METHODS: A consecutive series of 133 patients with melanoma brain metastases with regard to prognostic factors and the impact on survival were analyzed. RESULTS: 82 patients had involvement of only the cerebrum at the initial diagnosis, whereas in 7 patients only the cerebellum and the brainstem were involved. Seizures (n = 29) were the single most often reported symptom. The overall median survival time was 24 weeks (1-196) from diagnosis of brain metastases. Women had a significantly longer survival with 36 weeks (3-196) compared to 17 weeks (1-159) for men. Multivariate analysis has established as significant prognostic factors: female gender, number of brain metastases, surgery, chemotherapy, radiotherapy and corticosteroid application. CONCLUSION: With regard to the prognostic factors, an improved survival can be achieved in this patient group using more elective treatment options, also with emphasis on corticosteroids.

Complex combination biochemotherapy regimen in advanced metastatic melanoma in a non-intensive care unit: toxicity or benefit?

BACKGROUND: There is currently no chemotherapy or chemoimmunotherapy regimen that has shown impact on survival in patients with metastatic melanoma. Different biochemotherapy protocols showed promise with high response rates, but again without significant impact on survival. METHODS: We report the results of a retrospective analysis of a regimen consisting of dacarbazine, cisplatin, vindesine, interleukin-2 and interferon-alpha2b in 25 consecutively treated patients with regard to toxicity, efficacy and practicability. The treatment was performed on a regular dermatological ward. RESULTS: Grade III and IV toxicities were mainly haematological, with few cases of infection because of neutropenia seen. Best overall responses were CR 2/25, PR 2/25 and SD 9/25. The median progression free interval was 4 months (range 0-19) for all patients and the median survival time was 12 months (range 2-26). From a safety and practical point of view, there was no draw-back on treating patients in a non-intensive care unit. The median survival time is in the range of the one reported for monochemotherapy regimen. While there are some responding patients, the responses are short lived and go in parallel with high toxicity and impaired performance status. CONCLUSION: This complex and highly toxic chemoimmunotherapeutic regimen should not be considered as standard therapy in patients with metastatic malignant melanoma.

Large primary meningeal melanoma in an adult patient with neurocutaneous melanosis.

Neurocutaneous melanosis is often associated with melanoma of the central nervous system. Due to the inconspicuously looking cutaneous melanosis additional examinations are often not performed. We describe a patient with cutaneous melanosis who presented with neurological symptoms due to a large primary meningeal melanoma. The diagnosis of neurocutaneous melanosis was made. This case is an illustration of melanoma development in the central nervous system in a patient with cutaneous melanosis. This phenomenon should be kept in mind when observing patients with such skin lesions, even if they are of minor extent.