Allergic reactions to isosulfan blue during sentinel node biopsy--a common event.

BACKGROUND: Sentinel lymph node (SLN) dissection in the management of high-risk melanoma and other cancers, such as breast cancer, has recently increased in use. The procedure identifies an SLN by intradermal or intraparenchymal injection of an isosulfan blue dye, a radiocolloid, or both around the primary malignancy. METHODS: At the time of selective SLN mapping, 3 to 5 mL of isosulfan blue was injected either intradermally or intraparenchymally around the primary malignancy. From October 1997 to May 2000, 267 patients underwent intraoperative lymphatic mapping with the use of both isosulfan 1% blue dye and radiocolloid injection. Five cases with adverse reactions to isosulfan blue were reviewed. RESULTS: We report 2 cases of anaphylaxis and 3 cases of "blue hives" after injection with isosulfan blue of 267 patients who had intraoperative lymphatic mapping by the procedure described above. The 2 patients with anaphylaxis experienced cardiovascular collapse, erythema, perioral edema, urticaria, and uvular edema. The blue hives in 3 patients resolved and transformed to blue patches during the course of the procedures. CONCLUSIONS: The incidence of allergic reactions in our series was 2.0%. As physicians expand the role of SLN mapping, they should consider the use of histamine blockers as prophylaxis and have emergency treatment readily available to treat the life- threatening complication of anaphylactic reaction.

Prevention of breast cancer.

With the advent of screening and the increased incidence of breast cancer, concern for the prevention of breast cancer has become forefront in today's society. Determining individual risk is the key to prescribing prevention. Prevention of breast cancer is still under clinical investigation with only one drug, tamoxifen, showing benefit in high risk patients. This paper reviews the possible sites for prevention of neoplastic transformation via biomarkers in a breast cell as well as the investigational drugs and their potential use in the chemoprevention of breast cancer.

Extent of lumpectomy for breast cancer after diagnosis by stereotactic core versus wire localization biopsy.

BACKGROUND: Stereotactic core biopsy of mammographically defined breast abnormalities is an alternative to wire localization biopsy. The purpose of this study was to evaluate the extent of lumpectomy in patients diagnosed by stereotactic core versus wire localization biopsy. METHODS: A total of 67 consecutive patients diagnosed with invasive cancers or ductal carcinoma in situ (DCIS) were retrospectively reviewed. Thirty-four were diagnosed by core biopsy and the remaining 33 by wire localization biopsy. RESULTS: Approximately 65% of patients subsequently had breast-conserving surgical therapy. Seventy-nine percent of patients undergoing wire localization biopsies had positive surgical margins. Achievement of negative surgical margins for lumpectomies performed after wire localization or stereotactic core biopsies was 100% and 89%, respectively, which was not significantly different. However, the total volume of breast tissue removed for breast conservation in patients undergoing lumpectomy after wire localization versus core biopsies was 183 cm3 and 104 cm3, respectively, which was significantly different (P = .003). CONCLUSIONS: Diagnosis by stereotactic core biopsies resulted in less tissue removal to achieve margin-negative lumpectomies for breast conservation. Stereotactic core biopsy is the method of choice for biopsying nonpalpable, suspicious breast lesions.

Immunization of patients with melanoma peptide vaccines: immunologic assessment using the ELISPOT assay.

PURPOSE: Interest in the development of antimelanoma peptide vaccines has been renewed by the identification of specific epitopes recognized by tumor-infiltrating lymphocytes that mediate tumor regression after adoptive transfer. The human leukocyte antigen (HLA)-A2*0201-restricted, nonmutated melanocyte differentiation antigen gp100 has multiple T-cell epitopes, of which three are recognized by most gp100-reactive tumor infiltrating lymphocytes. Synthetic peptides based on two of these epitopes, or modifications to improve HLA binding affinity, were used individually to vaccinate patients with metastatic melanoma. The purpose of this study was to evaluate the success of the vaccinations, as determined by the results of enzyme-linked immunospot (ELISPOT) tests of individual immune cells. PATIENTS AND METHODS: The ELISPOT assay was used to measure the immunologic reactivity of peripheral blood lymphocytes from patients with metastatic melanoma before and after vaccination with gp100 peptides mixed with incomplete Freund's adjuvant. The peptides were g209 (ITDQVPFSV), g280 (YLEPGPVTA), modified g209 (g209-2M: IMDQVPFSV) or modified g280 (g280-9V: YLEPGPVTV) peptide. The patients' lymphocytes were tested by use of an ELISPOT assay for their ability to secrete interferon gamma with and without 12 days of in vitro sensitization with peptide. RESULTS: Patients were successfully vaccinated by gp100 peptides, as judged by the ELISPOT assays. Restimulation of the patients' lymphocytes in vitro with peptide for 12 days before the ELISPOT assay significantly amplified the immune activity. Increased immune activity after vaccination was specific for the immunizing peptide or its altered form, was major histocompatibility complex restricted, and was apparent against HLA-A2+, gp100+ melanoma cell lines and against T2 cells pulsed with the appropriate synthetic peptides. In general, the frequency of immune T cells was 10 to 100-fold higher in ELISPOT assays against peptide-pulsed T2 cells than against melanoma cell lines. Judged by the ELISPOT assays, vaccination was successful in six of seven patients injected with g209-2M when tested against g209-2M peptide and in five of these seven patients when tested against the native g209 peptide. Vaccination was also successful in five of six patients injected with g209, one of three patients injected with g280-9V, and four of seven patients injected with g280. Even without peptide restimulation in vitro before the ELISPOT assay, the frequency of immune T cells among fresh peripheral blood mononuclear cells tested 3 weeks after a second vaccination with g209-2M peptide was elevated in four of six patients and was about 1/1000 of cells tested against the same peptide pulsed onto T2 cells. DISCUSSION: Gp100 peptides were selected for vaccine development because they are epitopes recognized by tumor-infiltrating lymphocytes that are associated with tumor regression after adoptive immunotherapy in patients with metastatic melanoma. In the present study, most of the patients vaccinated with the gp209-2M peptide in incomplete Freund's adjuvant generated circulating antigen-specific immune T cells that could be detected by restimulation in vitro followed by an ELISPOT assay for individual cells secreting interferon gamma. The immune T cells reacted not only with the HLA-A2 restricted modified peptide but also with the native peptide and with melanoma cells that express gp100 and HLA-A2. Analysis of T-cell responses at the single cell level will be a valuable aid in assessing the effectiveness of melanoma vaccines and in determining optimal vaccine formulations and delivery.

The macrophage, TNF, and other cytokines.

A complex interplay of peptides known as the cytokines may have a tremendous influence over a number of inflammatory related conditions. Tumor necrosis factor occupies an early and central role in the initiation of cascades that ultimately influences a number of cell types involved in tissue inflammation, tissue rejection, cancer, and injuries from ischemia reperfusion. Only now are the cascades being defined and therapies being designed to interrupt the toxic effects of these cytokines and to treat malignancy.