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Biomedical subjects

D Nashan

Publications and source records attributed to D Nashan.

At least 19 recordsLinked to original sources
PubMed2007

[Skin tumors in organ-transplant recipients].

Skin cancers are a significant medical problem for organ-transplant recipients. Squamous cell carcinoma and basal cell carcinoma are most common tumors. An increasing incidence of melanoma, Kaposi sarcoma, Merkel cell carcinoma, as well as uncommon skin malignancies, is also seen. Predisposing factors include cumulative sun exposure, cumulative immunosuppression, age, gender, skin type, virus detection and genetic alterations. Skin tumors grow rapidly and their number continues to increase in the years following transplantation. Large numbers of tumors, aggressive courses and appearance in young patients are other characteristics of these skin tumors. More general awareness of the need for preventive measures and regular dermatological examinations is desirable. In addition standardized registries are needed to assure the comparability of data, to better correlate immunosuppression with skin tumors and to plan therapeutic studies.

Carcinoma↗
PubMed2007

Mycosis fungoides: a dermatological masquerader.

Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of MF can be difficult due to highly variable presentations and the sometimes nonspecific nature of histological findings. Molecular biology has improved the diagnostic accuracy. Nevertheless, clinical experience is of substantial importance as MF can resemble a wide variety of skin diseases. We performed a literature review and found that MF can mimic >50 different clinical entities. We present a structured framework of clinical variations of classical, unusual and distinct forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic (including syringotropic and folliculotropic) MF, MF with follicular mucinosis, granulomatous MF with granulomatous slack skin and papuloerythroderma of Ofuji are delineated in more detail.

Diagnosis, Differential↗
PubMed2005

Confetti-like lesions with hyperkeratosis: a novel ultraviolet-induced hypomelanotic disorder?

Confetti leucoderma can occur in a variety of unrelated skin disorders and is often a diagnostic challenge. We describe a 33-year-old man with a history of mycosis fungoides and vitiligo. He developed disseminated 1-2-mm round-shaped leucodermic lesions 6 months after psoralen photochemotherapy and 12 months after systemic therapy with interferon. The skin lesions had a discrete hyperkeratotic scale. Multiple skin biopsies and immunohistochemical studies showed lamellar orthohyperkeratosis, papillomatosis, hypomelanotic keratinocytes but a normal number of melanocytes. Langerhans cells, in contrast, were reduced in lesional skin. Electron microscopy disclosed only a few type I and II melanosomes in lesional melanocytes, while keratinocytes were largely devoid of any melanosomes. This constellation of clinical, immunohistochemical and ultrastructural findings has not been reported before and distinguishes our case from leucoderma punctatum, idiopathic guttate hypomelanosis and disseminated hypopigmented keratoses. We suggest that the skin lesions observed in our patient represent an unusual response to ultraviolet damage to melanocytes followed by reactive epidermal hyperkeratosis.

Adult↗
PubMed2004

[Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases].

The immune system plays an important role in the defense against malignant melanoma. Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) are therapeutically used for unspecific stimulation of the immune system. After intralesional injections of these cytokines into cutaneous melanoma metastases, regression has been observed. In view of its immunomodulating effects, imiquimod appears as an additional promising therapeutic option for treatment of malignant tumors. In a case report, we present combined therapy with intralesional IL-2, pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous metastatic malignant melanoma stage IIIa. This therapy achieved an almost complete remission. In a treatment period of eight months, side effects remained tolerable. Histologically, both fibrosis and inflammation were found in the regressing lesions. After the end of therapy, no disease progression occurred during 11 months follow-up.

Adjuvants, Immunologic↗
PubMed2003

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗
PubMed2003

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences.

BACKGROUND: A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated. PATIENTS AND METHODS: In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. RESULTS: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. CONCLUSION: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Adult↗
PubMed2003

Malignant melanoma and (18)F-FDG-PET: Should the whole body scan include the legs?

AIM: (18)F-FDG-PET (FDG-PET) is established in staging and follow-up of malignant melanoma. The legs are affected in 10-40% at time of diagnosis even if the primary is at the arms and torso. Imaging including the legs may detect distant manifestations but increases duration of the scan by approximately 30 min. We intended to disclose the diagnostic benefit of scanning the legs and to evaluate the therapeutic benefit resulting. PATIENTS, METHODS: In this retrospective analyse 213 consecutive PET studies of 153 patients with suspected or recent malignant melanoma were re-evaluated for metastatic spread by a blinded investigator. Histopathological follow-up was assessed for confirmation. RESULTS: Suspicious findings at the legs were depicted in 53 patients on 76 occasions. 38/53 showed pathologic uptake in the torso as well. In 15/53 patients it was restricted to the legs. One of them had a hitherto unknown, clinically relevant finding that was not apparent in palpation and inspection. In 6 other patients with primary location at the legs a validation of the positive PET findings was not possible up to now. CONCLUSION: Metastases and local recurrence of malignant melanoma at the legs were found in 41% of women and 27% of men. However, a long scan does not yield relevant additional data. We found isolated new manifestations at the legs in only 1/153 patients. We recommend performing a long scan only in patients with previous melanoma manifestations restricted to the legs. In all other cases a short scan of the torso and proximal thighs is sufficient. This allows a higher number of PET-scans without loss of diagnostic power and a shorter examination time.

Fluorodeoxyglucose F18↗
PubMed2002

[Persistent inflammatory reaction at the injection site of Il-2 with lymphoma-like inflammatory infiltrates].

Interleukin-2 (Il-2) is widely used for treatment of carcinomas, leukemia, and melanoma. Adverse drug effects of Il-2 include various systemic and generalized cutaneous drug reactions. In the following we report on a persistent inflammatory reaction at the injection site of Il-2. A patient received chemoimmuno-therapy for treatment of metastasizing melanoma, including subcutaneous application of recombinant interleukin-2 (Proleukin((R))). Within a few days reddish nodules developed at the injection sites that persisted after cessation of Il-2 injections for two years until final lethal outcome. Histologic examination revealed a lobular panniculitis expressing atypical lymphocytes and multinucleated histiocytes.

Aged↗
PubMed2002

[Malignomas following heart transplantation].

Up to 30% of patients with an organ transplantation develop precancerous lesions and malignant tumors, especially of the skin. All 241 patients who underwent heart transplantation from 1990 to 2000 were evaluated with regard to the development of neoplasias. Those alive in September 1999 were referred for a standardized dermatological exam (n=156) which detected malignancy in 28 patients being transplanted for 4.98 years on average. The skin was the organ most frequently involved (64%, n=18). 18% (n=5) of tumors were found in the urinary and genital tract, 7% (n=2) each in the respiratory and gastrointestinal tract, and 4% (n=1 ) in the breasts. The average age of patients who developed tumors was significantly higher as compared to the overall mean age (59.5+/-5 vs 49.8+/-14.7 years, p=0.00027). There was no correlation between development of malignancy and HLA matching, immunosuppressive drugs used, dosage and serum levels of immunosuppressive medication, and episodes of transplant rejection. Our study shows that the risk to develop tumors is at least doubled after heart transplantation. Due to the high incidence of skin tumors, transplant patients should undergo dermatological examinations on a regular basis.

Age Factors↗
PubMed2001

Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG).

In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.

Adolescent↗
PubMed2001

[Cytokines: current status and prospects in the treatment of skin tumors].

Various therapeutic options using cytokines have been described in the treatment of melanoma, T cell lymphoma, B cell lymphoma, squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma. The treatment regimens include cytokine substitution, cytokine induction, cytokine transfection and therapeutic cytokine constructs. In the adjuvant treatment of melanomas, IFN-alpha has become well established. Statistical evaluations of different adjuvant trials show that a significant prolongation of recurrence-free intervals can be achieved. IL-2 has a role in the therapy of advanced melanomas as well as in vaccination strategies. Further possible therapeutic immune modulations, which have been evaluated in experimental approaches and pilot studies, include treatment with IL-4, IL-7 and GM-CSF. Treatment with IL-12 promises to open new perspectives. A well established regimen in the treatment of T cell lymphoma stages Ia-IIb is the combination of PUVA and IFN-alpha. In vitro data also indicate an important (patho)physiological role for IL-12, so that this agent has been tested in phase I studies. IL-2, IFN-gamma, and the fused cytokine-toxin molecules DAB389IL-2 offer further therapeutic alternatives. B cell lymphomas are treated with antibody-IL-2 fusion proteins. Advanced or inoperable squamous cell carcinoma and basal cell carcinoma may be treated with local IFN-alpha injections. IFN-alpha or TNF-alpha may be considered for the treatment of recurrent or advanced Merkel cell carcinoma. In dermatological oncology cytokine treatment focuses on melanome an T cell lymphome. Cytokine application is mainly an integral part of multimodal regimens.

Animals↗
PubMed2001

[Endometrial metastasis of a "balloon" cell melanoma mimicking a "xanthomatous endometritis"].

Xanthomatous changes are unusual lesions of the corpus endometrium that may mask endometrial carcinoma. The term "xanthomatous endometritis" refers to morphological changes frequently induced by estrogen stimulation. We report for the first time a case of uterine metastasis of balloon-cell melanoma mimicking xanthomatous endometritis. Light microscopic, immunohistological, and ultrastructural results are presented and discussed in connection with our ideas on the pathogenesis of this peculiar tumor. The findings favor the hypothesis of a regressive phenomenon in the balloon-cell transformation of melanoma cells. The melan-A immunohistology seems to be more important in the diagnosis of balloon cell melanoma than the classic melanoma antibody HMB 45.

Diagnosis, Differential↗
PubMed2001

Diffuse melanosis arising from metastatic melanoma: pathogenetic function of elevated melanocyte peptide growth factors.

The origin of diffuse melanosis resulting from metastatic melanoma is unknown. We examined the light microscopic and ultrastructural changes in the skin of an affected 35-year-old woman and determined the peripheral blood levels of melanocyte growth factors. A total of 7 biopsy specimens were examined by light and electron microscopy and immunohistology (S-100, HMB45, MART1, CD68, MAC387). Serum/plasma levels of melanocyte growth factors of the patient were determined by enzyme-linked immunosorbent assays and compared with those of normal volunteers (n = 10) and amelanotic patients with metastatic melanoma (n = 10), matched to the UICC stage of the affected patient. Hyperpigmented but otherwise apparently normal skin of the patient displayed epidermal melanocyte hyperplasia, increased melanogenesis, and dermal pigment stored in histiocytes and other cells along with extracellular deposits. Blood levels of alpha-melanocyte stimulating hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated in the affected patient. Aberrant production of these factors may not only be responsible for activation of the pigment system in diffuse melanosis of metastatic melanoma, but also for increased proliferation, motility, and pigment incontinence of normal and malignant melanocytes.

Adult↗
PubMed2000

High dose inhalation interleukin-2 therapy for lung metastases in patients with malignant melanoma.

BACKGROUND: The lungs are a frequent site of metastasis in patients with melanoma, and this may cause respiratory problems in the terminal phase of the illness. Inhalation interleukin (IL)-2 therapy to the lung has been piloted and appears to be well tolerated. METHODS: Twenty-seven patients were treated with single agent dacarbazine and concurrent high dose inhalation IL-2 36 million IU per day). The patients previously had progressed on chemotherapy, predominately dacarbazine-based regimens. Patients included those with American Joint Committee on Cancer Stage IV melanoma, predominately those with lung metastases, but patients with extrapulmonary metastases also were allowed on the study. RESULTS: Five of the 27 patients experienced a complete pulmonary remission. Eight patients achieved a partial pulmonary remission, and 5 patients experienced stabilization of their disease. Eight patients developed pulmonary metastases. One patient was not evaluable. Four of the five patients who achieved a complete response and seven of the eight patients who achieved a partial response previously were treated with dacarbazine and progressed. There were no responses in extrapulmonary metastases. Side effects of treatment were minimal. The complete responses all were durable with a follow-up of 12 months, whereas patients with partial responses and stable disease progressed when IL-2 was discontinued. CONCLUSIONS: Inhalation therapy with IL-2 for pulmonary metastases from melanoma appears to be safe. The current preliminary study suggests efficacy although concurrent chemotherapy was given, thus confounding results to some extent. Therefore, these results need to be reproduced without concomitant chemotherapy. In addition, a strategy comprised of therapy with IL-2 inhalation until disease progression may prolong responses.

Administration, Inhalation↗
PubMed2000

[Control of section margins without any gaps in paraffin sections of melanoma of the face].

BACKGROUND AND OBJECTIVE: Malignant melanomas on sun-exposed skin are often poorly circumscribed and thus recur frequently. The aim of our clinical trial was to compare conventional to a modified micrographic surgery of primary melanoma. PATIENTS/METHODS: 28 patients with in-situ (n = 7) and invasive (n = 21) melanoma were treated with conventional surgical excision with wide margins; eight of these patients developed a local recurrence. In comparison, 20 patients with primary in-situ (n = 7) and invasive (n = 13) melanoma as well as four patients with recurrence after conventional surgery underwent modified micrographic surgery with delayed closure of the wound. RESULTS: Paraffin specimens of the margins revealed in half of the patients remnants of melanoma although excision was extended to non-lesional skin. Within a mean follow-up period of 21.3 months, none of our patients treated by modified surgery developed a recurrence. CONCLUSIONS: Local recurrencies of melanoma on sun exposed skin may be avoided by means of a modified micrographic surgery using permanent histologic sections.

Adult↗