• The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin—stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy. (Arch Surg.1992;127:392-399)

Technical details of intraoperative lymphatic mapping for early stage melanoma.

The concept of sun-reactive "skin typing" was created in 19751for a specific need: to be able to classify personswith white skinin order to select the correct initial doses of ultraviolet A (UVA) (in joules per cubic centimeter) in the application of the then newly developed technique for the treatment of psoriasis—oral methoxsalen photochemotherapy (PUVA).2The need arose as a result of experience with several patients who were a "dark" phenotype (brown or even black hair, and some with brown eyes) but, to our surprise, developed severe phototoxic reactions following oral ingestion of 0.6 mg/kg of methoxsalen and then, two hours later, were exposed to 4 to 6 J/cm2. These initial doses were obviously too high, and it was then understood that the estimation of the white-skinned person's tolerance level to oral PUVA could not be based solely on the phenotype (hair and eye color).

https://jamanetwork.com/journals/DERM/articlepdf/549509/archderm_124_6_008.pdf

The Validity and Practicality of Sun-Reactive Skin Types I Through VI

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of sa...

/pdf/final-version-of-the-american-joint-committee-on-cancer-4h72571lv0.pdf

Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (≤ 1 mm) melanomas; (2) in the N category, the following three independent factors were ide...

Prognostic Factors Analysis of 17,600 Melanoma Patients: Validation of the American Joint Committee on Cancer Melanoma Staging System

1.1 Photodynamic Therapy and Imaging
The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies.

PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow.






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Figure 1


(A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

/pdf/imaging-and-photodynamic-therapy-mechanisms-monitoring-and-76rc7acuq5.pdf

Imaging and photodynamic therapy: mechanisms, monitoring, and optimization.

Introduction biology and pathophysiology of skin disorders presenting in the skin and mucous membranes dermatology and internal medicine diseases due to microbial agents therapeutics paediatric and geriatric dermatology.

Dermatology in general medicine

..".surpasses the standards set in all [previous editions]"-Archives of Dermatology, review of prior editionWidely acclaimed dermatological treatise is completely revised and updated with over forty new chapters and an entirely new section on dermatologic surgery. Important new chapters include growth factors, thermoregulation, cell biology, vitiligo, albinism and more. Firmly places dermatology within the continuum of internal medicine and deploys over 1,600 exquisite color photos to depict clinical states.

Fitzpatrick's Dermatology In General Medicine

Oral administration of a photoactive drug, 8-methoxypsoralen (methoxsalen), followed by exposure to a high-intensity, longwave ultraviolet-light system resulted in complete clearing of generalized psoriasis in 21 patients. In 16 of these cases, a paired comparison showed methoxsalen followed by longwave ultraviolet light to be more effective than conventional ultraviolet light. 8-Methoxypsoralen followed by exposure to longwave ultraviolet light has previously been shown to inhibit epidermal DNA synthesis; this may be its mechanism of action in psoriasis, a disorder characterized by an accelerated cell cycle and rate of DNA synthesis. The term photochemotherapy is used to emphasize the point that the effect on epidermal proliferation and the therapeutic response require the interaction of light and drug. (N Engl J Med 291:1207–1211, 1974)

Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light.

ELANIN PIGMENTATION has aroused the curiosity and attention of man since the beginning of recorded history. This interest stems in part from the social, protective and cosmetic significance of pigmentation. In addition, much interest has arisen concerning the possible role of melanin formation in the development of the melanoma which has been described as having the most sinister reputation of malignant tumors (I). As Ewing (2) has stated, “The variations in pigment offer a very delicate indication of the functional activity of the cells and a unique opportunity to trace the relation between the functional activity and the growth capacity of the tumor cells.” As a result, this subject has attracted the attention of workers in many fields (3), for example, the cytologist in the study of the melanin granules; the geneticist, the anthropologist and the biologist in a study of the relationship of heredity, environment and nutrition to the development of pigment; and the organic and biologic chemists in the study of the chemical mechanism underlying melanin formation. In the past quarter of a century several comprehensive reviews on the mechanism of melanin formation have appeared (~-II), but in only a few of these has there been any consideration of the biochemical aspects of this problem. No attempt was made to connect the processes of melanin formation operating in various species. Different mechanisms were proposed for humans, lower animals and plants. Investigation of the biochemistry of melanin formation in plants, insects and marine animals had shown that the enzyme tyrosinase catalyzes the oxidation of L-tyrosine to dihydroxyphenyl L-alanine (dopa) and then the oxidation of dopa to melanin.

Thomas B. Fitzpatrick

Papers

Dermatology in general medicine

Fitzpatrick's Dermatology In General Medicine

The Validity and Practicality of Sun-Reactive Skin Types I Through VI

Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light.

Biochemistry of melanin formation