Organ- and treatment-specific local response rates to systemic and local treatment modalities in stage IV melanoma

BACKGROUND: Metastatic melanoma shows different local response rates in organs to systemic or local treatment modalities. Whereas skin, soft tissue, lymph node and lung metastases seem to have better local response rates, the local response of metastases localized in the liver, brain and bone seems to be low. OBJECTIVES: The organ-specific response rate, local response rate of each therapeutic measure and survival of 68 patients with stage IV disease were evaluated. METHODS: Four hundred and ten treatment periods (1-18 per patient) in 17 different organs of 43 men and 25 women (mean age 55 years, range 19-79) with measurable, widespread, surgically incurable disease were analysed. Chemotherapy was given in 405 of 410 treatment periods with dacarbazine, fotemustine, vindesine, carboplatin and temozolomide in different schedules. Local treatment modalities comprising radiotherapy, gamma knife radiosurgery and local hyperthermia were given in 71 of 410 treatment periods. RESULTS: Local response (complete or partial local remission) was achieved in 52 treatment periods (12.7%). When local treatment modalities, either combined with systemic therapy or not, were compared with systemic therapeutic modalities alone, a local response of 24% was achieved with local measures, compared with 10% in systemic treatment only (P = 0.003). When a spontaneous remission rate of less than 5% is considered, however, local as well as systemic treatments had a significant effect (P < 0.001). Organ-specific response rates to local therapies showed no statistically significant differences between the various organs involved. When systemic treatments without local measures were taken into account, lung metastases, cutaneous/subcutaneous metastases and adrenal metastases performed significantly better than liver metastases. When different treatment modalities were considered, there was no significant difference between the three local measures applied (radiotherapy, gamma knife radiosurgery and hyperthermia). Among the systemic therapies, dacarbazine high dose and carboplatin monochemotherapy were superior to combined regimens using fotemustine. A local response, irrespective of the mode of therapy, was significantly associated with longer survival (median 16 months) compared with no local response or local progressive disease (median 7 months; P < 0.0001). When the first treatment period of each patient was considered, local response was no longer a significant predictor. CONCLUSIONS: The study shows that local therapeutic measures are superior in inducing a local response than systemic therapies alone. Induction of remission may be associated with longer survival. Chemotherapy, despite limited local response rates, is still statistically superior to an estimated spontaneous remission rate.     

Ocular melanoma: epidemiology, clinical presentation and relationship with dysplastic nevi

PURPOSE: Ocular melanoma is a rare entity compared to cutaneous malignant melanoma. We examined the frequency of the tumor in a defined geographic region, its clinical presentation and its relationship with dysplastic nevi in 136 patients. METHODS: 136 patients (64 men and 72 women; mean age 61.7 years, range 20-92 years) with ocular melanoma were treated at the University Hospital of Graz between June 1996 and December 2001. 129 had primary uveal melanoma in one eye (117 choroidal melanomas, 11 melanomas of the ciliary body and 1 of the iris), 2 patients had uveal melanoma in both eyes, 4 patients had conjunctival melanoma and 1 patient had a melanoma of the lacrimal sac. Epidemiology, history, potential risk factors, clinical presentation and relationship with dysplastic (= atypical) nevi were documented. RESULTS: 48 patients (35.3%) showed more than five dysplastic nevi, compared to only 1.2% in the general population (chi(2) test: p < 0.001). 5 (3.7%) had additional cutaneous melanoma and 7 (5.1%) had a family history of melanoma. The lifelong risk for the occurrence of an additional primary cutaneous melanoma was 2.9%, which is significantly higher than the usual estimate of 1% for the general population. CONCLUSIONS: Patients with primary ocular melanoma have an increased risk to develop cutaneous melanoma and should therefore be examined regularly by dermatologists.     

Economic burden of illness imposed by severe sepsis in Austria

INTRODUCTION: Sepsis is a life-threatening disease, requiring instant treatment in an intensive care unit (ICU). The aim of this study was to determine the direct and indirect costs occurring in Austria due to this disease. PATIENTS AND METHODS: Direct costs were calculated based on a retrospective chart analysis in four adult Austrian ICUs, evaluating 74 patient records from the years 2000/2001. Patients were identified to have suffered from severe sepsis using ACCP-definitions. Assessed resource use (medication, laboratory analysis, microbiology analysis, consumer-goods, diagnostic procedures, staff costs, and basic bed costs) was linked with related center specific costs to determine direct costs per patient. Indirect costs due to productivity losses were calculated using official statistical material. RESULTS: The mean length of ICU stay (LOS ICU) of a severely septic patient was 18.1 days. Overall ICU mortality was found to be 43.2% and showed no gender difference. The mean daily direct ICU costs of care for severely septic patients were [symbol: see text] 1,617 and the mean total direct ICU costs per septic patient were [symbol: see text] 28,582. In total costs, survivors were equally expensive as non-survivors ([symbol: see text] 28,699 vs. 28,463) although their length of study was considerably longer (21.9 vs. 13.2 days). Considering a range of patients with severe sepsis in Austria from 6,700 to 9,500 per year, total direct costs in Austria range from [symbol: see text] 192 million to [symbol: see text] 272 million. Indirect costs determined by productivity losses due to unfitness for work (temporary and permanent) and premature death amount to [symbol: see text] 484 million to [symbol: see text] 686 million in Austria per year (same incidence range). Total costs, i.e. burden of illness, combining direct costs with indirect costs, range from [symbol: see text] 676 million to [symbol: see text] 958 million. CONCLUSION: Patients with severe sepsis have a high mortality rate, spend prolonged periods of time in the ICU, and are expensive to treat. Indirect costs of severe sepsis due to productivity losses, particularly by premature death, are considerable.     

The influence of lunar phenomena on the incidence of emergency cases

It is widely believed that the incidence of specific emergency cases shows clustering during long observation periods. Though there is no scientific proof, many physicians and other emergency staff believe in influences of the moon or the signs of the zodiac. The aim of our retrospective study over 6 years was to evaluate (a) if there are any statistically documented peaks of frequency of emergency cases at all, and (b) if they can be linked to lunar phenomena. We evaluated all three aspects of the moon: The 'synodic' moon (=lunar phases), the 'sideric' moon (=distance between moon and the earth) and the moon in her relation to the signs of the zodiac (=influence of the zodiac). A total of 11134 patients entered the study. We found highly significant clusters of emergency calls, mainly for lung disorders. However, neither aspect of the moon showed the slightest correlation with the frequency of emergency calls (sideric month (P=0.99), synodic month (P=0.85) and zodiac (P=0.85)). Trigonometric regression with the period of the anomalistic month (P=0.173) and with the synodic month (P=0.28) did not show any influence of the moon on emergency in either cases. Though our retrospective data analysis documented clustering of emergency cases, any influence of the moon and the signs of the zodiac can be definitely ruled out.     

Transferrin receptor expression in normal skin and in various cutaneous tumors

In the majority of human cells the transferrin receptor (TFR) plays an important role by mediating the cellular iron uptake. The TFR is especially expressed by proliferating cells and has been found in high amounts in malignant tumors. The distribution of the TFR in frozen sections of 89 skin biopsies of normal skin and of various cutaneous tumors was investigated using an anti-TFR monoclonal antibody (OKT9) and a 3-step immunoperoxidase method. Our results indicate that in normal human skin the TFR shows a characteristic microanatomical distribution in the basal cell layer correlated to the architectural pattern of the dermal-epidermal interface. In cutaneous lymphomas of high grade malignancy the TFR was expressed in virtually all cells compared to only 25-75% in low grade lymphomas. Malignant melanomas were strongly positive in the whole tumor tissue, whereas benign melanocytic nevi were largely negative. Obviously the immunohistochemical demonstration of the TFR may serve as prognostic indicator or diagnostic aid, respectively.     

In vivo reflectance confocal microscopy of erythematosquamous skin diseases

Background:  In vivo reflectance confocal microscopy (RCM) represents a promising imaging tool that allows a non-invasive examination of skin morphology in real time at nearly histological resolution, showing microanatomical structures and individual cells.
Objectives:  The aim of our study was to evaluate the diagnostic accuracy of confocal examination of erythematosquamous skin diseases, to define typical RCM-features and assess them for their presence or absence, diagnostic performance and reliability.
Methods:  Three independent observers received standardized instructions about diagnostic RCM-features of erythematosquamous skin diseases. A total of 1700 RCM images obtained from 75 patients with psoriasis, contact dermatitis, mycosis fungoides, chronic discoid lupus erythematosus (CDLE) or subacute cutaneous lupus erythematosus (SCLE) and from 10 'healthy adults' without any skin disease were evaluated by each observer.
Results:  Overall, sensitivity and specificity values as observed by three observers were, respectively, 89.13% and 95.41% for psoriasis; 83.33% and 92.31% for contact dermatitis; 62.96% and 94.53% for SCLE/CDLE; and 63.33% and 92.89% for mycosis fungoides.
Conclusions:  Reflectance confocal microscopy examination appears to be a promising method for non-invasive assessment of erythematosquamous skin diseases. This study provides a set of well-described morphological criteria with obvious diagnostic impact, which should be used in further investigations.     

Kutane Angiosarkome

Hintergrund und Fragestellung. Kutane Angiosarkome entwickeln sich in den meisten F?llen 1. idiopathisch im Kopf-Hals-Bereich ?lterer Menschen, 2. im Bereich l?nger bestehender Lymph?deme (lymph?demassoziierte Angiosarkome) oder 3. an Stellen, die vorher bestrahlt wurden (bestrahlungsinduzierte Angiosarkome). Angiosarkome werden einerseits sehr h?ufig – sowohl klinisch als auch histopathologisch – verkannt, andererseits sind wegen der extrem schlechten Prognose dieser Tumoren Früherkennung und Therapie ?u?erst wichtig. In der vorliegenden Arbeit werden Probleme bei der Diagnose von kutanen Angiosarkomen aufgezeigt, prognostische Faktoren diskutiert sowie auf die Effektivit?t verschiedener Therapiem?glichkeiten hingewiesen.     

Primitive neuroectodermal tumor arising in the skin. Differentiation from neuroendocrine carcinoma of the skin.

We report a 25-year-old male patient with primitive neuroectodermal tumor presenting as a subcutaneous tumor on the right buttock, which was initially diagnosed as neuroendocrine carcinoma of the skin. Subsequently, local recurrence and metastatic spread to the lung occurred. The tumor was resistant to highly aggressive chemotherapy. The patient died 6 months later with severe pulmonary and lymph node involvement.