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D Nashan

Publications and source records attributed to D Nashan.

At least 19 recordsLinked to original sources
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↗
PubMed1999

[Cutaneous myiasis--a vacation souvenir].

Cutaneous myiasis is a temporary infestation of the skin with fly larvae. Travelling to subtropical areas accounts for a higher risk and increasing incidence in Europeans. In Middle- and South American myiasis is mainly caused by the botfly (Dermatobia hominis). Blood-suckling arthropods, usually mosquitoes, transmit the larvae of the botfly via phoresis, a unique mechanism of egg deposition. In Africa cutaneous myiasis is mostly due to the tumbu fly (Cordylobia anthropophaga). Infection with the tumbu fly larvae occurs after direct contact with the eggs that are often deposited in clothes and towels. Clinically an abscess-like lesion develops. Creeping sensations of movement under the skin are occasionally described. Following hatching, spontaneous healing can normally be expected, although extraction of the larvae is recommended to prevent abscess formation and superinfection.

Adult↗
PubMed1998

[Adult-onset Still's disease and its characteristic rash].

Still's disease was originally described as one form of rheumatoid arthritis in children beginning with fever and other systemic symptoms. In rare cases it may also begin in the adult and is then referred to as adult-onset Still's disease. The diagnostic criteria include typical rash, arthralgias, bouts of fever, and leukocytosis, as well as lymphadenopathy or splenomegaly, liver dysfunctions, noninfectious angina, and absence of rheumatoid factor and antinuclear antibodies. We report two adult patients with longstanding disease whose exanthema guided us to the correct diagnosis. The rash is a finding with high sensitivity. It is characterized by red macules with distinct borders and is evanescent. During an acute flare of the rash, gentle friction induces erythematous, isomorphic (Koebner) phenomena, which, as we describe here for the first time, may persist longer than the remainder of the fleeting rash.

Adult↗
PubMed1997

[Therapy studies in dermatologic oncology. Recommendations for patient education].

Guidelines of good clinical practice regulate controlled clinical studies. Goal of the study, type of treatment and possible side effects have to be explained. The physician faces problems, if the study includes a "no treatment group". Referring to the literature and based on our own experience with tumor patients, several criteria are proposed to optimize the recruitment of patients. Important points are: Explanations should be given by an experienced doctor. He must be informed about the study and therapeutic alternative treatments. The atmosphere for the talk must be quiet. The participation of a person whom the patient trusts is desirable. The necessity of the study must be explained. Randomization in different study groups should be discussed without any preference. Prognosis should be explained without any detailed statistical data. Form of treatment, possible side effects and control examinations have to be discussed. The family physician's cooperation should be stressed. Personal autonomy in the patient's decision to participate in the study must be emphasized. Enough time for reflection must be granted before the final decision. It must be assured that the patient receives the same medical attention even after rejecting the study. These recommendations might help to avoid major mistakes which are harmful for the doctor-patient-relationship and further tumor therapy. A good initial discussion forms the basis for effective cooperation during tumor treatment. It may counteract the personal fear and negative reports in media of being "a guinea pig". The patient will appreciate the efforts of the doctor to provide optimal therapy. Furthermore, he will realize that such studies are necessary to improve future therapies.

Humans↗
PubMed1997

[Treatment of lung metastases from malignant melanoma with IL-2 inhalation therapy].

Seven patients with pulmonary metastases of malignant melanoma were treated with inhalation therapy with 36 million IU interleukin-2 for six months. Inhalation therapy was combined with four bolus infusions of DTIC at a dose of 850 mg/m2 once every four weeks. Response rates were 71.4% with 2 patients achieving a complete remission (CR), 2 partial remissions (PR), 1 stable disease (SD), and 2 progressing disease (PD). Therapy was well tolerated with low toxicity. Six of the patients developed cough; one patient was slightly feverish. We conclude that inhalation therapy of lung metastases is a promising addition to the therapeutic arsenal against malignant melanoma.

Administration, Inhalation↗
PubMed1997

A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosiform erythroderma.

Annular epidermolytic ichthyosis has recently been delineated as a distinct clinical phenotype within the spectrum of epidermolytic keratinization disorders. The pattern of inheritance of the disorder is consistent with an autosomal dominant mode of transmission. Here we report a second incidence of this disorder in a family with two affected generations. The proband suffered from bullous ichthyosis and had bouts of disease activity associated with the development of numerous annular and polycyclic erythematous, hyperkeratotic plaques on the trunk and the proximal extremities. Histologic examination showed the typical pathology of epidermolytic hyperkeratosis, and ultrastructural analysis revealed abnormal keratin filament networks and tonofilament clumping with a perinuclear distribution. Molecular analysis revealed a novel tandem CG to GA 2-bp mutation in the same allele of keratin 10 in affected individuals, resulting in an arginine to glutamate substitution at residue 83 (R83E) of the 2B helical segment. We conclude that annular epidermolytic ichthyosis should be considered a variant of bullous congenital ichthyosiform erythroderma.

Adult↗
PubMed1995

[Life threatening angioedema caused by acquired C1 inhibitor deficiency associated with paraproteinemia and livedo racemosa].

A 61-year-old patient with life-threatening angioneurotic oedema was found to have an acquired C1-inhibitor (C1-INH) deficiency. In addition to lowered serum levels of C1-INH (both protein concentration and enzymatic activity), C2, C4 and CH50, which are characteristic for the hereditary form of angioneurotic oedema, markedly lowered C1q was found, which is typical for the acquired form. There were no antibodies against C1-INH. Repeated thorough examination disclosed no neoplasm, though the presence of neoplasm has often been reported to be associated with the acquired C1-INH deficiency. However, the patient showed persistent paraproteinaemia and paraproteinuria and developed livedo reticularis. Treatment with danazol resulted in a rise of the complement fraction levels and cessation of angioneurotic oedema. Paraproteinaemia and livedo reticularis persisted unchanged.

Angioedema↗