Aggressive angiomyxoma: multimodality treatments can avoid mutilating surgery.

Aims: Aggressive angiomyxoma is a soft-tissue tumour of the pelvi-perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. In search of alternative treatment methods we present our experience in seven patients.

Isolated limb perfusion for an irresectable melanoma recurrence in a Jehovah's witness.

Isolated limb perfusion (ILP) is a treatment option for irresectable melanoma lesions, because with ILP 20-fold higher concentrations of chemotherapy can be achieved locally than is systemically possible and high response rates are subsequently achieved. Jehovah's witnesses do not accept any form of blood transfusion, either autologous or homologous blood or only blood products. The use of an extracorporeal circuit, without the use of any blood products is acceptable for Jehovah's witnesses.

Differential effects of matrix and growth factors on endothelial and fibroblast motility: application of a modified cell migration assay.

Cell migration is crucial in virtually every biological process and strongly depends on the nature of the surrounding matrix. An assay that enables real-time studies on the effects of defined matrix components and growth factors on cell migration is not available. We have set up a novel, quantitative migration assay, which enables unharmed cells to migrate along a defined matrix.

Contralateral recurrence and prognostic factors in familial non-BRCA1/2-associated breast cancer.

Background: A higher incidence of contralateral breast cancer and ipsilateral recurrence has been reported in familial breast cancer than in sporadic cancer. This study investigated the influence of contralateral cancer and tumour stage on survival in patients with familial non-BRCA1/BRCA2-associated breast cancer.

Methods: The incidences of contralateral breast cancer, ipsilateral recurrence, distant disease-free and overall survival were assessed in 327 patients from families with three or more breast and/or ovarian cancers, but no BRCA1 or BRCA2 gene mutation (familial non-BRCA1/2), and in 327 control subjects with sporadic breast cancer, matched for year and age at detection.

Changing the pathophysiology of solid tumours: the potential of TNF and other vasoactive agents.

Solid tumour therapy with chemotherapeutic drugs is hampered by a number of factors resulting in poor results and failure of initially promising drugs. From the application of Tumour Necrosis Factor alpha in the melphalan-based Isolated Limb perfusion some lessons could be learned. Most importantly, combination of treatment approaches, certainly when multiple targets are involved, increases the effectiveness of the therapy.

Sentinel node biopsy for clear cell sarcoma.

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described.

Randomized trials in melanoma: an update.

No effective therapy for metastatic melanoma exists. Polychemotherapy or chemoimmunotherapy have not shown survival benefits. Vaccines have shown little activity in stage IV disease.

Influence of pegylated interferon-alpha therapy on plasma levels of citrulline and arginine in melanoma patients.

The aim of this study was to evaluate the effect of pegylated interferon-alpha (PEG-IFN-alpha) on the plasma citrulline/arginine ratio, regarded as an index of nitric oxide (NO) synthesis, in patients with high-risk melanoma. Forty patients were randomly assigned to either PEG-IFN-alpha treatment (n = 22) or to observation only (control group, n = 18). The treatment group received 6 microg PEG-IFN-alpha/kg once a week during 8 weeks, followed by a maintenance dose of 3 microg/kg/wk.

Intratumoural expression of TNF-R1 and EMAP-II in relation to response of patients treated with TNF-based isolated limb perfusion.

Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical response.

TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility.

Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The current use of TNF in cancer is in the regional treatment of locally advanced soft tissue sarcomas and metastatic melanomas and other irresectable tumors of any histology to avoid amputation of the limb.

Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study.

Background: Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined.

Gene expression profiling of primary cutaneous melanoma and clinical outcome.

Background: Gene expression profiling data for human primary cutaneous melanomas are scarce because of the lack of retrospective collections of frozen tumors. To identify differentially expressed genes that may be involved in melanoma progression and prognosis, we investigated the relationship between gene expression profiles and clinical outcome in a cohort of patients with primary melanoma.

Methods: Labeled complementary RNA (cRNA) from each tissue sample was hybridized to a pangenomic 44K 60-mer oligonucleotide microarray.

Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement.

Aim: To analyse causes of failure of sentinel node (SN) procedures in breast cancer patients and assess the role of pre-operative ultrasound examination of the axilla.

Methods: In 138 consecutive clinically node negative breast cancer patients with the primary tumour in situ a SN procedure with radiolabeled colloid and blue dye was performed. Radioactivity in the SN was scored as inadequate or adequate.

Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma.

Background: Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma (STS) of the limb. As it has become apparent that amputation for STS does not improve survival rates, the interest in limb-preserving approaches has increased. Isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) and melphalan is successful in providing local tumor control and enables limb-preserving surgery in a majority of cases.

Isolated limb perfusion for melanoma patients--a review of its indications and the role of tumour necrosis factor-alpha.

Aims: The treatment of melanoma in-transit metastases (IT-mets) can vary widely and is dependant on the size and the number of the lesions. When multiple, large lesions exist, isolated limb perfusion (ILP) has established itself as an attractive treatment option with high response rates.

Methods: Review on the various methods of treatment of melanoma in-transit metastases, with a focus on isolated limb perfusion.

Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma.

Purpose: A pegylated interferon, peginterferon alfa-2a (PEG-IFNalpha-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNalpha. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNalpha-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system).

Patients And Methods: PEG-IFNalpha-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 mug (n = 49) once weekly for 24 weeks, with maintenance therapy for responders.

Technology insight: Utility of TNF-alpha-based isolated limb perfusion to avoid amputation of irresectable tumors of the extremities.

Isolated limb perfusion (ILP) with melphalan is effective in the treatment of small multiple melanoma intransit metastases and is utilized widely for this indication. The treatment is much less effective against bulky melanoma metastases and has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor-necrosis factor-alpha (TNF-alpha) to this treatment approach has changed the situation dramatically.

Cytokines and vascular permeability: an in vitro study on human endothelial cells in relation to tumor necrosis factor-alpha-primed peripheral blood mononuclear cells.

Tumor response is strongly enhanced by addition of tumor necrosis factor (TNF)-alpha to chemotherapy in local-regional perfusion. TNF primarily targets the endothelial lining of the tumor-associated vasculature, thereby improving permeability of the vascular bed. This augments uptake of the coadministered chemotherapeutic drug in the tumor.

5-Year follow-up of sentinel node negative breast cancer patients.

Aim: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients.

Methods: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated.

Repeat isolated limb perfusion with TNFalpha and melphalan for recurrent limb melanoma after failure of previous perfusion.

Aim: To assess the effectiveness of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) and melphalan for recurrent or persistent melanoma lesions after previous ILP.

Methods: Between 1978 and 2001, 21 patients (mean age 65, range 29-83 years) underwent repeat ILP for recurrent or persistent melanoma after a previous ILP. First ILPs had been performed with melphalan alone in 13 patients and with addition of TNFalpha in eight, for a median of nine lesions (interquartile (IQ) range 2-23 lesions).

High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma.

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS.

[Preventive surgical prcedures for inherited risk of breast cancer].

Preventive surgical procedures for inherited risk of breast cancer Forwomen with a demonstrated BRCA1 or BRCA2 mutation, the cumulative risk of developing invasive breast cancer before the age of 70 years is about 50-85% and the risk of developing invasive epithelial ovarian cancer is 20-60%. Regular surveillance including physical examination and imaging is offered to mutation carriers and the options for risk-reducing surgery are discussed. Although bilateral prophylactic mastectomy is a drastic intervention, it significantly reduces the incidence of breast cancer.