Biomedical subjects
Publications and source records attributed to H K Koh.
Multiple strategies are required to combat the increasing incidence and mortality of cutaneous melanoma. Major questions about melanoma and skin cancer are reviewed, with particular attention to education and early detection.
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It is apparent that multiple end points are required to adequately describe the response to therapy for CTCL. Investigators may differ as to which end points are best suited for their data. In general, multiple end points provide a better overall view of response to treatment as compared with a single end point. Regardless, measures of response and end points should be clearly defined and the methods of calculating end points clearly stated.
Cutaneous T-cell lymphoma (CTCL) encompasses a constellation of diseases of malignant clonal T lymphocytes that present initially in the skin. Within this disease spectrum, mycosis fungoides, and the Sézary syndrome are best known. Progress in the understanding of the T-cell malignancies now places other clinical entities within this disease classification. The authors review the epidemiology and clinical manifestations of CTCL.
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Evidence from several countries suggests that the long-continued increase in melanoma-related mortality is slowing or has ceased. In some countries, decreasing rates are now seen particularly in women. These trends are probably due to successful primary prevention and early diagnosis. However, incidence continues to increase, even in areas of already high incidence such as Australia. Sun exposure has been established as the major cause of cutaneous melanoma in white patients, and no other environmental factors show a consistent association. Links to occupation, diet, and hormonal factors are still not clearly established. The frequency of nevi is likely to be both a good indicator of future melanoma risk and a short-term biologic marker of the effects of sun exposure; valuable new studies on the latitude gradient and natural history of nevi have been published. Primary prevention of skin cancers is now a priority in high-risk countries, and studies in Australia are clarifying the effect of education on sun exposure behavior. Although surveillance of particularly high-risk persons is valuable, the benefits of more widespread targeting or screening of high-risk persons remains unclear. Useful studies on the reliability of diagnostic and screening examinations have been produced, along with preliminary data on the value of diagnostic aids such as epiluminescence microscopy.
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Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.
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BACKGROUND: Cutaneous T-cell lymphoma (CTCL) comprises a spectrum of presentations, including erythroderma, pruritus, lymphadenopathy, and circulating atypical lymphocytes. Photopheresis is an extracorporeal treatment in which white blood cell concentrates are subjected to UV irradiation when the serum methoxypsoralen level is above 50 ng/mL. Of patients with CTCL, those with erythroderma have been most responsive to this therapy. In some conditions, including certain malignant hematologic neoplasms, serum soluble interleukin 2 receptor levels (SIL2R) correlate with disease activity. We sought to determine whether serum SIL2R levels correlated with disease activity in six erythrodermic patients with CTCL treated primarily with photopheresis. We measured SIL2R levels in five patients with stage III or greater erythrodermic CTCL and one with stage IIa CTCL. We compared SIL2R values with clinical course, skin scores, CD4/CD8 ratios, peripheral white blood cell counts, and Sézary cell counts, using Pearson correlation coefficients. OBSERVATIONS: The SIL2R levels correlated with clinical course and skin scores, even when controlled for other factors noted above. CONCLUSION: Data preliminarily suggest that serum SIL2R levels may be useful indicators of disease activity in erythrodermic CTCL patients treated with photopheresis.
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Because extracorporeal photopheresis has been shown to be clinically effective in Sezary syndrome, a disease characterized by a circulating malignant clone, we initiated a pilot study of its use in B-cell chronic lymphocytic leukemia (B-CLL) to see if it could be similarly effective. We treated three patients with Rai stage III and IV B-CLL with photopheresis (3 consecutive days a week every 3 weeks) and followed serial clinical and immunologic parameters. While we noted no major toxicity, there was neither clinical response to treatment nor marked improvement in white counts or mitogen assays. We conclude that photopheresis was not effective in inducing remission in this pilot study of advanced stage B-CLL patients.
BACKGROUND: First-degree relatives of patients with melanoma are roughly two to eight times more likely than the general public to be diagnosed with melanoma. Several organizations recommend regular screening for these and other persons at high risk for melanoma. However, there are no data as to how frequently such persons receive skin cancer examinations. OBJECTIVE: Our purpose was to determine the current screening recommendations and practices of dermatologists regarding family screening for melanoma. METHODS: With a one-page questionnaire, we surveyed dermatologists attending a 1989 meeting of the New England Dermatological Society. RESULTS: Seventy-three dermatologists completed the questionnaire. Most dermatologists (70%) reported that they encouraged screening of family members of patients with melanoma but also reported that family members infrequently appeared for skin examinations. CONCLUSION: Although most dermatologists encouraged screening of first degree relatives of melanoma patients, there appears to be infrequent acceptance by the patient of these recommendations. Recording family screening in the patients' charts, reminders to patients, and distributing literature on familial melanoma may increase acceptance by the patient of these recommendations.
BACKGROUND: Melanoma is external and potentially detectable by many persons but little is known about who first discovers these lesions. An understanding of discovery patterns can shape future public and professional education programs. OBJECTIVE: Our purpose was to assess patterns of melanoma discovery and to determine the patients' role in finding their own lesions. METHODS: With a written, mailed questionnaire, we conducted a population-based statewide survey of 216 incident cases of melanoma in Massachusetts. RESULTS: Approximately half (53%) of melanomas were self-discovered, whereas the remainder were detected by medical providers (26%), family members (17%), and others (3%). Nearly one third of persons said they could not see their own lesions easily. Compared with men, women were more likely to discover their own lesions (66% vs 42%, p = 0.001) and those on their spouses (23% vs 2%, p less than 0.001). CONCLUSION: Improving early detection and reducing mortality of melanoma will require both public and professional education programs, with particular emphasis on targeting men at highest risk of this disease.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.