Werner Kempf

Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure

OBJECTIVES The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure (CHF). BACKGROUND Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase (iNOS) in the myocardium and peripheral skeletal muscles has been described in CHF. METHODS Twenty male patients with stable CHF (left ventricular ejection fraction 25 +/- 2%; age 54 +/- 2 years) were randomized to a training group (n = 10) or a control group (n = 10). At baseline and after six months, serum samples and vastus lateralis muscle biopsies were obtained. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1-beta levels were measured by enzyme-linked immunosorbent assay, local cytokine, and iNOS expression by real-time polymerase chain reaction. RESULTS Exercise training improved peak oxygen uptake by 29% in the training group (from 20.3 +/- 1.0 to 26.1 +/- 1.5 ml/kg. min; p < 0.001 vs. control group). While serum levels of TNF-alpha, IL-6, and IL-1-beta remained unaffected by training, local skeletal muscle TNF-alpha decreased from 1.9 +/- 0.4 to 1.2 +/- 0.3 relative U (p < 0.05 for change vs. control group), IL-6 from 71.3 +/- 16.5 to 41.3 +/- 8.8 relative U (p < 0.05 vs. begin), and IL-1-beta from 2.7 +/- 1.1 to 1.4 +/- 0.6 relative U (p = 0.02 vs. control group). Exercise training also reduced local iNOS expression by 52% (from 6.3 +/- 1.2 to 3.0 +/- 1.0 relative U; p = 0.007 vs. control group). CONCLUSIONS Exercise training significantly reduced the local expression of TNF-alpha, IL-1-beta, IL-6, and iNOS in the skeletal muscle of CHF patients. These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

Abstract:  The new WHO/EORTC classification for cutaneous lymphomas comprises mature T‐cell and natural killer (NK)‐cell neoplasms, mature B‐cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior.

EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma

Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs.

CD30+ lymphoproliferative disorders: histopathology, differential diagnosis, new variants, and simulators.

Summary:  CD30+ lymphoproliferative disorders of the skin (CD30+ LPD) represent a well‐defined spectrum of primary cutaneous T‐cell lymphomas which have been recognized as distinct entities in recent lymphoma classifications. Lymphomatoid papulosis and anaplastic large‐cell lymphoma share the expression of CD30 antigen as a common phenotypic hallmark but differ in regard to their clinical and histologic features as well as their biologic behavior. This article summarizes the histologic features of CD30+ LPD and presents recently identified new clinicopathologic variants of CD30+ LPD. There is an increasing number of reactive inflammatory disorders and neoplastic diseases which are composed of or contain a significant number of CD30+ cells and mimic LyP or anaplastic large cell lymphoma clinically or histologically. Differential diagnostic considerations focus on other lymphoproliferative processes with CD30+ tumor cells as well as non‐lymphoid neoplasms and inflammatory simulators. The term CD30+ pseudolymphoma is proposed to designate inflammatory processes with CD30+ T cells. The final diagnosis of CD30+ LPD is based on a synthesis of clinical, histologic, phenotypic, and molecular genetic findings.

Topical photodynamic therapy in the treatment of actinic keratoses and Bowen’s disease in transplant recipients

Background. Transplant recipients (TR) have a dramatically increased risk for widespread epithelial neoplasms of the skin. Thus, there is a need to treat initial stages of these neoplasms such as actinic keratoses (AK) and Bowen’s disease (BD) to prevent progression to invasive and potentially fatal squamous cell carcinoma. Topical photodynamic therapy (PDT) has been proven to be an effective treatment for AK and BD in immunocompetent patients, but no prospective trials in immunocompromised TR have been performed so far. Methods. Twenty TR and 20 controls with histologically confirmed AK or BD underwent either a single or two consecutive treatments of topical PDT in an open trial. The application of 20% 5-aminolevulinic acid (ALA) for 5 hours was followed by illumination with 75 J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source. Results. The overall complete response rates in TR at 4, 12, and 48 weeks were 0.86, 0.68, and 0.48, respectively. The cure rates in both patient groups were comparable at 4 weeks but were significantly lower in TR than in controls at 12 and 48 weeks (P <0.05). Side effects included erythema, edema, and crust formation after illumination. Cosmetic results were excellent without scar formation or alterations in pigmentation. Conclusions. Topical PDT with 20% 5-ALA is an effective and safe treatment for AK and BD in immunosuppressed TR, with initial response rates comparable with those in immunocompetent patients. It is particularly useful in TR because of the possibility for repeated treatment of large lesional areas.

A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients.

Background  Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma.

Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization For Research and Treatment of Cancer (EORTC)

BACKGROUND Granulomatous cutaneous T-cell lymphomas (CTCLs) are rare and represent a diagnostic challenge. Only limited data on the clinicopathological and prognostic features of granulomatous CTCLs are available. We studied 19 patients with granulomatous CTCLs to further characterize the clinicopathological, therapeutic, and prognostic features. OBSERVATIONS The group included 15 patients with granulomatous mycosis fungoides (GMF) and 4 with granulomatous slack skin (GSS) defined according to the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Patients with GMF and GSS displayed overlapping histologic features and differed only clinically by the development of bulky skin folds in GSS. Histologically, epidermotropism of lymphocytes was not a prominent feature and was absent in 9 of 19 cases (47%). Stable or progressive disease was observed in most patients despite various treatment modalities. Extracutaneous spread occurred in 5 of 19 patients (26%), second lymphoid neoplasms developed in 4 of 19 patients (21%), and 6 of 19 patients (32%) died of their disease. Disease-specific 5-year survival rate in GMF was 66%. CONCLUSIONS There are clinical differences between GMF and GSS, but they show overlapping histologic findings and therefore cannot be discriminated by histologic examination alone. Development of hanging skin folds is restricted to the intertriginous body regions. Granulomatous CTCLs show a therapy-resistant, slowly progressive course. The prognosis of GMF appears worse than that of classic nongranulomatous mycosis fungoides.

Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas.

Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.

Baseline staging in cutaneous malignant melanoma.

Background  Baseline staging in patients with primary cutaneous malignant melanoma (MM) is routine, but the diagnostic accuracy and the impact on clinical outcome are still unclear.

Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis

Nephrogenic fibrosing dermopathy (NFD) is a rare fibrosing skin disease of unknown etiology occurring in patients with terminal renal disease. It was first described in the year 2000. The histology of NFD shows an increased number of dendritic cells, fibroblasts and thickened collagen fibers resembling scleromyxedema. It can be distinguished from scleromyxedema by a different distribution pattern of the skin lesions with indurated plaques mainly on the extremities and the absence of paraproteinemia. As yet, no treatment for NFD has been proven to be uniformly efficient. We describe the case of a 40-year old patient with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of extracorporeal photopheresis.