Secular trends in adult male smoking from 1992 to 2006 in South Korea: age-specific changes with evolving tobacco-control policies.

OBJECTIVES: For years, South Korea has had one of the highest levels of tobacco use among males in the world, but a steady decline has been observed recently. This study examined how the smoking behaviour of male adults changed with age after the implementation of national tobacco control policies in 1995. STUDY DESIGN: Repeated cross-sectional study using a national survey. METHODS: Data were obtained from the 1992, 1995, 1999, 2003 and 2006 results of a repeated cross-sectional survey, the Social Statistics Survey. The smoking status of adult men was compared before (1992 and 1995 surveys) and after (1999, 2003 and 2006 surveys) the implementation of government-directed tobacco control policies using graphical methods and logistic regression analysis. RESULTS: After the implementation of tobacco control policies, the percentage of current male smokers decreased while the percentage of former smokers increased markedly. Smoking prevalence among older men (aged 50 years or more) reduced initially, and this decline was more pronounced after the tobacco control policies were implemented. Smoking prevalence in younger men (aged 30-49 years) declined in 2003 when more comprehensive tobacco control policies were implemented. CONCLUSIONS: This study suggests that comprehensive tobacco control policies in South Korea reduced smoking prevalence among males, initially among older men and later among both older men and younger men.

Influence of estrogen administration on tumor characteristics and survival in women with cutaneous melanoma.

A prospective study on 289 women with clinical stage I cutaneous melanoma was done to determine the relationship between estrogen administration, tumor characteristics, and survival. Eighty-two women took oral contraceptives (OC) and 44 took menopausal estrogens (MPE) prior to the diagnosis of melanoma. Users of OC presented with thinner primary tumors than nonusers of OC (P less than .01). A similar trend was observed in users of MPE. Women who used OC in the year prior to the diagnosis of melanoma had statistically thinner tumors than those who had discontinued use of OC more than 1 year prior to diagnosis (P less than .025). A statistically significant preponderance of truncal lesions was observed among users of OC (P less than .01). Other tumor characteristics were unaltered by estrogen administration. Duration of use and time in relation to diagnosis of melanoma did not affect survival. Women who took hormones had slightly better 5- and 9-year survival rates than nonusers. These results suggest that prior estrogen use and, particularly, use of OC in women developing melanoma have no deleterious effect.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Prognosis of clinical stage I melanoma patients with positive elective regional node dissection.

We tested 12 clinical and histologic variables to see which ones best predicted death from melanoma in 66 patients with positive elective regional node dissections (clinical stage I, pathologic stage II [CSI, PSII]). Despite the presence of lymph node metastases, not all patients had poor prognoses. Patients with tumors less than or equal to 3.5 mm and a percentage of positive nodes less than or equal to 20% had a 7-year survival rate of 66%. Within this low-risk group the subset with primary lesions on the trunk or extremities (except hands and feet) had a 7-year survival rate of 76%. This compares with poor 7-year survivals of 29% and 30% observed in other defined high-risk groups. Our results confirm and extend earlier observations concerning the prognoses of CSI, PSII melanoma patients and are relevant to any ongoing and future studies concerning elective regional node dissection (ERND) or adjuvant therapy trials in melanoma.

Lentigo maligna melanoma has no better prognosis than other types of melanoma.

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

The efficient workup of suspected lung cancer.

The triage process of patients with suspected cancer of the lung is reviewed, paying particular attention to areas of inefficiency and delay. Most patients with suspected lung cancer are inoperable and can be triaged on presentation. The efficient workup involves confirmation of diagnosis and simultaneous determination of stage and operative status. The physician should search for common sites of metastatic spread, with pragmatic use of biopsies and scans. From the outset, the physician should also pay special attention to the patient's functional status, attitude toward possible surgery, and cardiopulmonary status, with the goal of quickly directing each patient to proper therapy.

T-cell chronic lymphocytic leukemia. Report of a case studied with monoclonal antibody.

A previously healthy 74 year old woman presented with T-cell chronic lymphocytic leukemia, lymphadenopathy, hepatosplenomegaly and a mediastinal mass. The circulating lymphocytes were small to medium in size (some with convoluted nuclei) and W rosette-positive; they could be assigned to the inducer-helper subset of T cells with the acid of monoclonal antisera. These cells reacted with OKT3, which detects peripheral T cells; OKT4, which detects the inducer-helper subset of T cells; and OKT11, which detects the sheep cell receptor. It is noteworthy that they were also positive for the la-like antigen found on T cells only after activation. Microscopic examination of a lymph node biopsy specimen revealed a diffuse pattern of pleomorphic large cells characteristic of the T-cell lymphomas and lymphocytic leukemias reported from Japan. However, the lymph node cells lacked the T-cell differentiation antigens present on the circulating lymphocytes. The findings in this case provide insight into the pathogenesis of this unusual disorder and are relevant to our understanding of the spectrum of surface antigens in the more common malignant lymphomas.

Prognosis in Stage 1 malignant melanoma: seven-year follow-up study of splenic radiocolloid uptake as predictor of death.

In an earlier study we found that patients with clinical Stage 1 and 2 cutaneous malignant melanoma and increased splenic radiocolloid uptake had more frequent recurrence at 24 mo, compared with melanoma patients having normal liver-spleen scintigrams. This report, an 80-mo follow-up study, gives further information on 119 clinical Stage 1 patients. Fifteen of 35 patients with increased splenic uptake (42.9%) died from melanoma as opposed to only 16 of 84 (19.1%) with normal liver-spleen images (p less than 0.01). Multivariate analysis showed that augmented splenic uptake of technetium-99m sulfur colloid is a marker for adverse prognosis in patients with malignant melanoma but does not appear to be an independent variable in predicting death. In clinical Stage 1 patients, increased splenic uptake correlated significantly with pathologic stage (positive elective node biopsy) as well as thickness and mitotic rate in patients with thicker lesions. It may be that patients with thicker, pathologically aggressive tumors have an increased splenic blood flow and/or enhanced immune and reticuloendothelial response (as manifested by abnormal liver-spleen scintigram). If so, the enhanced immune response does not appear to contribute to overall survival.

Preventive strategies and research for ultraviolet-associated cancer.

Ultraviolet (UV)-associated cancer is the most common cancer in the United States. Approximately 90% of nonmelanoma skin cancer and 65% of melanoma are attributable to UV exposure and theoretically could be eliminated by primary prevention measures. Safe sun strategy includes use of sunscreens, use of protective clothing, minimization of exposure from 10 A.M. to 3 P.M., and avoidance of tanning parlors. Although more definitive data in human populations on the effectiveness of sunscreens to prevent melanoma and skin cancer are needed, sunscreens are thought to reduce risk. Safe sun prevention must start in childhood and adolescence when people receive most of their UV exposure. Secondary prevention through professional and public education and early detection may further reduce melanoma mortality.

Do pediatricians counsel families about sun protection?: a Massachusetts survey.

BACKGROUND: Pediatric visits during summer months may be especially opportune times for sun protection counseling for children and their parents. Few data exist on the extent of such counseling. OBJECTIVE: To begin to assess this, we surveyed practicing Massachusetts pediatricians to examine current attitudes and practices of sun protection counseling. DESIGN AND SETTING: Surveys mailed to Massachusetts pediatricians. RESULTS: We received surveys from 756 (60%) of 1263 eligible Massachusetts pediatricians. Almost 70% indicated that they recommended safe sun practices to more than 50% of their patients and their parents during the summer months. Counseling regarding seat belt use, bicycle helmet use, and smoking prevention were ranked higher in priority than sun protection counseling by pediatricians; nutritional guidelines were noted by pediatricians to be a parent's most frequent concern. Four variables were independently associated with a practitioner's providing safe sun recommendations to more than 50% of parents and children: (1) private setting and health maintenance organization practitioners as opposed to academic physicians, (2) high ranking of patients' safe sun knowledge, (3) high priorities of both parents and physicians for sun protection counseling and parental knowledge of safe sun practices relative to other recommendations, and (4) pediatrician interest in receiving instructional materials. CONCLUSIONS: For the most part, summer sun protection counseling among Massachusetts pediatricians seems well integrated into standard practice. Most pediatricians rated their confidence level as high for discussing sun protection and only a few cited inadequate training or poor reimbursement as barriers toward improved counseling. Small steps, such as providing more instructional materials to patients and using office-based reminder systems, may improve the quality of sun protection counseling practices. Incorporating sunburn prevention into the list of routinely recommended injury prevention guidelines for pediatricians should be considered.

Genetically engineered transgenic plants with the domain 1 sequence of tobacco mosaic virus 126 kDa protein gene are completely resistant to viral infection.

In many plant RNA viruses, Domains 1, 2 and 3 are conserved in replicase proteins. In order to examine the interference of viral replication by the Domain 1 sequence, we generated transgenic plants transformed with DNA corresponding to the Domain 1 sequence of the TMV 126 kDa protein. This DNA sequence includes the TMV RNA from nucleotides 1 to 2,149, which comprises both the 5'-untranslated and methyl transferase region. The transgenic plants obtained showed complete resistance to TMV infection. The presence of the Domain 1 sequence in the plants completely prevented local necrosis in Nicotiana tabacum cv. Xanthi nc, and any systemic development of symptoms in Nicotiana tabacum Xanthi upon TMV inoculation. Most transgenic plants sustained the conferred resistance even under TMV inoculum concentrations up to as high as 1,000 microg/ml. To detect any accumulation of TMV coat protein or viral RNA in infected transgenic plants, immunochemical tests and Northern blot analyses were carried out. Neither viral RNA or coat protein was detectable in the systemic leaves of the completely resistant transgenic plants, whereas they were accumulated in large quantities in all of the control plants. Because of the conservation of Domain 1 in many plant RNA viruses, the acquisition of resistance to virus infection using the Domain 1 sequence appears to be a very effective strategy for breeding of viral resistant plants.

Public health interventions for melanoma. Prevention, early detection, and education.

Worldwide melanoma control programs that include some combination of primary prevention, education, and screening activities have only recently begun to undergo an evaluation process. More studies with rigorous design and evaluation are needed. Until then, the proper public health policy guidelines for melanoma control, especially screening, are open to debate. Future studies must determine how screening, early detection, case finding, and education can best be used to reduce mortality and achieve optimal melanoma control.

Epidemiology and clinical manifestations of cutaneous T-cell lymphoma.

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.

Assessing clinical outcomes in cutaneous T-cell lymphoma.

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.

Factors associated with smoking among children and adolescents in Connecticut.

INTRODUCTION: The age of smoking initiation has dropped over the past four decades. Since behaviors and attitudes adopted in late childhood or early adolescence predict future smoking, it is important to understand the smoking and other risk-taking behaviors and attitudes of children aged 12 and younger. The goal of the analyses presented here was to describe behavioral and attitudinal factors associated with smoking among elementary school (grades 4-6), middle school (grade 7-8), and high school (grades 9-12) students in Connecticut. METHODS: We have used data from 8 years (1988-1996) of an anonymous, self-administered health risk appraisal survey given to children and adolescents in self-selected public and private schools. We compared the proportion of smokers and nonsmokers who reported various behaviors and attitudes and compared them with the chi-square test. RESULTS: Fifteen percent (n = 4,884) of the total population (n = 31, 861) were current smokers. At all grade levels, current smokers were more likely than nonsmokers to engage in risk-taking behaviors, and to report more stress and depression. Indicators of risk-taking and stress were also associated with the intent to smoke among children in grades 4-6. CONCLUSIONS: Smoking occurs within the context of other risk-taking behavior and psychological distress, among both children and older adolescents. Our data provide support for the idea of early identification and targeting of children at high risk of smoking in elementary school, possibly as early as grade four.

Use of health services before diagnosis of head and neck cancer among Boston residents.

One hundred thirty incident cases of head and neck cancer in Boston between September 1, 1985, and March 31, 1988, provided interview or medical record review data on the use of health services in the 24 months preceding the diagnosis of cancer. One hundred twenty-four subjects were able to recall whether and how often they visited health care sites in this period, reporting a median number of 10.5 visits; 94% recalled at least one visit. Eighty-nine medical record reviews indicated a median of seven visits. For the most part, these visits were to providers whom subjects considered their regular source of care--sources that provided care in a broad range of locations. These data support a strategy of integrating screening for head and neck cancers into existing health care services.

Malignant fibrous histiocytoma arising from discoid lupus erythematosus.

While the association of discoid lupus erythematosus (DLE) and subsequent squamous cell carcinoma is well known, there are no reports in the English-language literature concerning the association of DLE and soft-tissue sarcoma. We describe a patient with DLE and malignant fibrous histiocytoma.

Serum soluble interleukin 2 receptor levels in erythrodermic cutaneous T-cell lymphoma correlate with response to photopheresis-based treatment.

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.

Melanoma control in the United States: current status.

Screening and education for melanoma/skin cancer are receiving increasing worldwide attention. In an attempt to improve melanoma control in the United States, where incidence and mortality rates continue to increase, the American Academy of Dermatology (AAD) has provided free skin cancer screenings to more than 600,000 Americans and prevention messages to millions more. This chapter reviews and summarizes ongoing melanoma control activities in the United States, including prevention, education, and early detection/screening. We also address outcome measures in melanoma control and suggest that the unique external and visible nature of skin cancer blurs the distinction between screening and education. Measuring and evaluating the benefits of international melanoma control activities presents many challenging tasks. Future collaborative work must include complementary strategies in melanoma/skin cancer prevention, education, and screening to combat the worldwide increase in melanoma incidence and mortality.

Etiology of melanoma.

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.