Biomedical subjects

N Dubin

Publications and source records attributed to N Dubin.

At least 19 recordsLinked to original sources

PubMed2000

Risk of breast cancer and organochlorine exposure.

A prospective investigation of breast cancer and organochlorine (OC) exposures was undertaken in the New York University Women's Health Study. Cases (n = 148) and individually matched controls (n = 295) were identified among women whose blood had been obtained 6 months or more prior to breast cancer diagnosis. In addition, among 84 cases and 196 controls, two or more consecutive annual blood samples were available to estimate half-lives of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethene (DDE) and polychlorinated biphenyls (PCBs). Cases and controls had similar levels of DDE (geometric mean, 6.95 versus 7.27 ng/ml; lipid-adjusted geometric mean, 977 versus 1100 ng/g) and PCBs (5.04 versus 4.97 ng/ml; lipid-adjusted geometric mean, 683 versus 663 ng/g). These differences remained nonsignificant when estrogen receptor status of tumors was considered. DDE and PCB half-lives did not differ in case versus control patients. In control patients, DDE and PCB half-lives were strongly correlated (r(s) = 0.71), and the half-life of DDE (but not that of PCB) was inversely correlated with body mass index (BMI), yet the blood serum levels of PCB (but not those of DDE) were correlated with BMI. We conclude that there is no evidence for an association of breast cancer risk with DDE or PCB levels in blood (based on samples collected during the period 1987-1992) nor with their elimination half-lives. However, changes in DDE and PCBs over time are influenced by metabolism, BMI, and current OC exposures, and each may affect interpretation of OC levels in risk assessment models.

Adult↗

PubMed1998

Serum autoantibodies recognizing 5-hydroxymethyl-2'-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women.

Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer.

Adult↗

PubMed1997

Poly(ADP-ribose) polymerase in human breast cancer: a case-control analysis.

The importance of a genetic polymorphism (A/B allele) of poly(ADP-ribose) polymerase (PARP) pseudogene on chromosome 13q34-qter, and PARP enzyme activities in the development of human breast cancer were evaluated in a cancer case-control study. A total of 309 Caucasian women (> or = 50 years old) were evaluated for the PARP genotype, 70 of whom had histologically confirmed breast cancer, 128 women with benign breast diseases as study controls, and 111 reference controls. Age was significantly associated with case-control status (p < 0.0001), but family history of breast cancer, age at menarche, age at first live birth and parity were not. The frequency of the PARP B allele was similar in breast cancer cases (0.14), study controls (0.13), and reference controls (0.15). In a subset of 14 breast cancer cases and 32 study controls, the mean PARP enzyme activities (induced by H2O2 or oligonucleotide) were observed to be lower in cancer cases; an age-adjusted odds ratio of 3.40 (95% confidence interval = 0.70-19.54) for the below-median oligonucleotide-induced PARP was suggestive of an association. In subjects with the AB or BB genotype, the mean H2O2-induced PARP enzyme activity was significantly higher (p = 0.02, adjusted for case-control status and age) compared with that in subjects with the AA genotype. These findings indicate that: (a) the genetic polymorphism of the PARP pseudogene on chromosome 13 is not associated with the development of breast cancer in our study population; (b) oligonucleotide-induced PARP activity may be useful for identifying postmenopausal women at increased risk for breast cancer; and (c) there is a possible functional link between the genotype of the PARP pseudogene and enzyme activation.

Aged↗

PubMed1996

Study design and sample size considerations for half-life studies.

Most studies on the half-lives of environmental contaminants have been based on small sample sizes and a limited number of repeated measurements. In this paper, we address issues of study design and sample size for half-life studies. Useful guidelines are provided for choosing the number of repeats and the optimal time interval between repeats for estimating an individual's half-life with a given level of precision, while minimizing the cost of the study. In addition, sample size and power considerations for studies comparing two population half-lives are investigated. An example is presented using data from a study on polychlorinated biphenyls and breast cancer.

Breast Neoplasms↗

PubMed1996

Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities.

In a randomized double-blind trial of alpha-tocopherol (vitamin E), we investigated the effects of alpha-tocopherol supplementation on lipid- and water-soluble antioxidants in plasma and DNA repair activities in peripheral mononuclear leukocytes. Baseline levels of antioxidants and DNA repair activities were assessed twice before alpha-tocopherol intervention: on day 1 (visit 1) and day 3 (visit 2). During the second visit, participants were randomized to receive one of three dosages of alpha-tocopherol, 15, 60, or 200 mg/day for 4 weeks. The same biochemical measurements as at baseline were repeated twice after intervention: on day 17 (visit 3) and day 31 (visit 4). A total of 31 healthy volunteers were eligible for the study, completed all four visits and were included in the final data analysis. At baseline, no appreciable differences of dietary intake of vitamin E and plasma alpha-tocopherol were observed among the three dosage groups. In general, supplementation of alpha-tocopherol for 2-4 weeks resulted in a dose-dependent increase of plasma level of alpha-tocopherol (compared to baseline); significant increases of plasma alpha-tocopherol at visits 3 and 4 were observed in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. At visit 4 (but not visit 3), plasma glutathione levels were significantly elevated (compared to baseline) in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In addition, there was an increase in the lipid protection ratio by supplementation of alpha-tocopherol for 2-4 weeks in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In general, there were no consistent effects of alpha-tocopherol on DNA repair activities in peripheral mononuclear leukocytes after being adjusted for baseline DNA repair activities. Results from this study demonstrate the interrelationship between alpha-tocopherol and other antioxidants in plasma; total plasma antioxidants can be modulated by short-term dietary supplementation of alpha-tocopherol.

Adult↗

PubMed1995

Increased prevalence of K-ras oncogene mutations in lung adenocarcinoma.

Reported estimates of ras mutation prevalence in lung adenocarcinoma of 15-24% may be underestimates because of the insensitivity of the assays used. We have devised a rapid, non-radioactive assay for ras mutations, which detects 1 mutant allele/10(3) normal alleles and have used it to study DNA isolated from 53 lung tumor samples (including 28 adenocarcinomas) previously analyzed by PCR/allele specific oligonucleotide hybridization, which is less sensitive. We detected mutations in 13 of 28 samples, including 7 not detected by PCR/allele specific oligonucleotide hybridization. We also found ras mutations in 14 of 25 previously unstudied samples (56%). Our results indicate that the prevalence of K-ras codon 12 mutations in lung adenocarcinoma is higher than previously reported; thus, ras mutations may be more clinically useful as molecular markers for lung cancer than has been appreciated.

Adenocarcinoma↗

PubMed1995

The effects of hydrogen peroxide on DNA repair activities.

Oxygen free radicals generated by H2O2 are involved in the multistage carcinogenic process; mechanisms include carcinogen activation, oxidative DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H2O2 in carcinogenesis--modulation of DNA repair activities. Preexposure of human peripheral mononuclear leukocytes to H2O2 significantly inhibited DNA repair activities in response to damage induced by N-methyl-N'-nitro-N-nitrosoguanidine, measured as unscheduled DNA synthesis. The responses to H2O2 were compared in four healthy human subjects with two sample preparations on different days. Results from multivariate general linear models showed that H2O2 significantly inhibited DNA repair in a dose-dependent manner after adjustment for between- and within-subject variabilities. There was an estimate of 5.0 units (dpm/5 x 10(5) cells) decrease in induced unscheduled DNA synthesis per unit (microM) increase of H2O2 treatment. Furthermore, there was substantial variability in DNA repair activities for the same individual sampled on different days regardless of H2O2 dose level. Results from this study suggest that H2O2 not only can induce DNA damage, but also have suppressive effects on DNA repair.

Adult↗

PubMed1994

Estimation and sample size considerations for clustered binary responses.

Although there is much literature on sample size determination for clinical trials or experiments with independent responses, there is a lack of methodology to obtain sample sizes for dependent outcomes. This paper presents a simple way to calculate sample size for estimating treatment effects and diagnostic accuracy in the case of correlated binary outcomes. The proposed weighted procedure also has use in estimation, whose advantages we demonstrate through simulation. Recommendations are made for practical application.

Clinical Trials as Topic↗

PubMed1994

Estimation of time since infection using longitudinal disease-marker data.

We propose a method to estimate the usually unknown time since infection for individuals infected with human immunodeficiency virus type 1 (HIV-1). If we assume the time since infection has an exponential prior distribution, then under the model the conditional distribution of time since infection, given the CD4 level at the time of the first positive HIV-1 antibody test, is a truncated normal density. We applied the method to prevalent cohort data both from intravenous drug users and from homosexual/bisexual men. For the intravenous drug users the estimated mean time since infection was 15.0 months from infection at a presumed mean CD4 level of 1060 cells/ml to first positive antibody test at a CD4 level of 597 cells/ml, which was the average CD4 at enrollment for infected subjects. For the homosexual/bisexual men the estimated mean time since infection was 16.7 months from infection at a presumed mean CD4 level of 699 cells/ml to first positive antibody test at an average CD4 level of 577 cells/ml. We performed a validation study using initially seronegative subjects in these cohorts who seroconverted to HIV-1-positive antibody status during the follow-up period. For the intravenous drug users, data were too few to provide definitive verification of the method. In the cohort of homosexual/bisexual men, however, there was a total of 70 seroconverters with relevant data. Among them, the median absolute difference between the midpoint of the known seroconversion interval and the estimated mean infection date was 4.6 months, conditional on CD4-lymphocyte measurements taken approximately 18 months subsequent to infection. Conditional on CD4 approximately 30 months after infection, this median difference increased modestly to 8.2 months. Our analysis suggested that the underlying mathematical model tends to overestimate short times since infection and underestimate long times since infection. We consider potential corrective modifications to the model.

Bias↗

PubMed1994

No improvement in survival from melanoma diagnosed from 1973 to 1984.

BACKGROUND: While the incidence and mortality of melanoma has increased dramatically during the last few decades, survival rates, based on the case-fatality ratio, have apparently improved. Efforts at early detection have probably been effective in the discovery of lesions at a curable stage. However, the effects of lead-time bias need to be accounted for in order to understand the contribution of early detection to the increased incidence. This can best be done by appropriately controlling for depth of the tumour or a surrogate of depth, at diagnosis. METHODS: A survival analysis was conducted for 3197 Connecticut residents newly diagnosed with invasive melanoma between 1973 and 1984. Five prognostic variables were evaluated: sex, age at diagnosis, anatomical site, histological type, and year of diagnosis. RESULTS: As expected, women and the young had better survival than men and the elderly. Melanomas located on the trunk had poorer prognosis than those on other sites. The survival experience by histological type was significantly different; lentigo maligna melanoma and superficial spreading melanoma had the best survival and nodular melanomas the poorest, while 'other' and unclassifiable melanomas had intermediate survival. When survival by period of diagnosis was controlled by other variables, which included surrogates for disease stage, there was no improvement in survival over time. CONCLUSION: These data do not imply that early diagnosis and treatment are ineffective; rather, that within stages of disease, survival improvements did not occur during the period 1973-1984.

Adolescent↗

PubMed1993

Blood levels of organochlorine residues and risk of breast cancer.

BACKGROUND: Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. PURPOSE: This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. METHODS: We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. RESULTS: Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. CONCLUSION: In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. IMPLICATIONS: These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide.

Adult↗

PubMed1993

Prediction of histologic melanocytic dysplasia from clinical observation.

BACKGROUND: The dysplastic melanocytic nevus (DMN) is a putative precursor for malignant melanoma in persons with a family history of melanoma and multiple large atypical moles. Furthermore, the concept that DMN confers increased risk for melanoma has been extended to those without a family history of melanoma. Some investigators have characterized DMN in terms of size, surface topography, and irregularity of border and color and have provided definitive statements as to major and minor clinical "criteria" for DMN. OBJECTIVE: In this study we conducted a quantitative test of previously described clinical characteristics in patients diagnosed with melanoma but without a family history of melanoma in a first-degree relative (N = 153). METHODS: Two of us examined each patient independently, counting the total number of nevi, deciding on the most clinically atypical nevus, and recording quantitatively the size, surface, border, and color characteristics. The most atypical nevus was removed from each patient and diagnosed histologically without knowledge of the clinical examiner's description. RESULTS: Of the 153 nevi so examined, 91 (59.5%) were judged to be clinically atypical and 23 nevi (15%) were classified as histologically dysplastic. We then analyzed the ability of each clinical feature to predict histologic melanocytic dysplasia. A multivariate analysis was conducted with the blindly scored clinical features as independent variables. Independent variables included total number of nevi and freckles as well as the features of the particular nevus biopsied (including longest diameter, macular component, irregular border, ill-defined border, haphazard coloration). Of the many independent clinical variables, only total number of nevi and macular component were useful in the final multivariate prediction. Of 21 nevi with a macular component removed from persons with more than 24 total body nevi, 7 were histologically dysplastic, representing a positive predictive value of 33.3% (95% exact confidence limits 14.6% to 57.0%). Of the 38 nevi without a macular component to their most atypical nevus removed from patients with 12 or fewer total body nevi, 37 failed to meet histologic criteria for DMN, representing a negative predictive value of 97% (95% exact confidence limits 86.2% to 99.9%). CONCLUSION: We conclude that in nonfamilial melanoma, clinical criteria suggesting DMN when present will often fail to display histologic melanocytic dysplasia. In contrast, absence of a macular component in melanocytic nevi in a person with fewer than 13 total body nevi will accurately predict the absence of melanocytic dysplasia on histologic examination.

Adult↗

PubMed1993

HIV risk-related sexual behaviors among heterosexuals in New York City: associations with race, sex, and intravenous drug use.

OBJECTIVE: To investigate the relationship between heterosexual behaviors associated with HIV infection and ethnicity, sex, and intravenous drug use. METHODS: Subjects were recruited from Bellevue Hospital Center, New York City between 1986 and 1989, and interviewed about sexual behaviors and intravenous drug use. Analyses were based on 1561 black, white, or Hispanic individuals who reported having sexual contact with a member of the opposite sex. RESULTS: Twenty-seven per cent of the study population were black, 43% Hispanic, and 31% white. Blacks were more likely than whites or Hispanics to have initiated sexual intercourse at an early age, and to have had a sexually transmitted disease. Sex with a female drug user was more common among white men, and contact with a prostitute more frequent among Hispanic men. Among the women, Hispanics had fewer sexual risk factors overall than whites or blacks. Use of barrier contraceptives was uniformly low across all ethnic groups. Intravenous drug use was significantly associated with sexual risk-taking. Women were more likely than men to have an intravenous drug-using (IVDU) sexual partner. CONCLUSIONS: The large prevalence of high-risk sexual practices observed in this study emphasizes the continuing need to target AIDS prevention programs at those at highest risk of heterosexually transmitted HIV: racial minorities, IVDU, and their sexual partners.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Heterosexual transmission of HIV in a cohort of couples in New York City.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Adolescent↗

PubMed1991

Case-control evaluation of breast cancer screening efficacy.

The feasibility and validity of using case-control methods to evaluate the efficacy of breast cancer screening were investigated using data from the Health Insurance Plan of Greater New York Breast Cancer Screening Trial. Women who died of breast cancer were compared with individually matched controls of the same age who had equal or greater survival times. To minimize the effects of self-selection bias, most analyses focused on the 95 cases and 380 matched controls who had been screened at least once and for whom covariate data were available. A statistically significant effect for being screened more than once versus being screened once, uncorrected for healthy-screenee bias, was found (odds ratio = 0.13, p less than 0.001). After correction for healthy-screenee bias, the effect was not statistically significant (odds ratio = 0.54, p = 0.15). Possible explanations for this statistical nonsignificance are: 1) correction for healthy-screenee bias entails loss of power and 2) the correction procedure used may, under some circumstances, result in bias toward the null hypothesis. Further research into means of eliminating healthy-screenee bias is needed to improve the applicability of case-control methods to the evaluation of screening efficacy.

Adult↗

PubMed1991

CD4% is the best predictor of development of AIDS in a cohort of HIV-infected homosexual men.

To determine the relationships between individuals' baseline T-cell subsets, their rates of change with time, and AIDS-free survival time, data were collected at 6-monthly intervals from 379 HIV-seropositive homosexual Sydney men, of whom 31 developed AIDS during the 3-year observation period. Both CD4% and rate of change of CD4% in an individual had significant prognostic value in determining AIDS-free survival time. Compared with subjects whose CD4% remained stable, subjects whose CD4% dropped by 7% or more in a year had a relative hazard of 35.1 (95% confidence interval = 11.7-105.6, P less than 0.001) of developing AIDS. Increasing CD4% had a significant protective effect, reducing the risk of developing AIDS. CD4%, CD4 cell count and CD4: CD8 ratios showed steeper declines in subjects who were later diagnosed with AIDS than in those who remained AIDS-free. The rates of immunological change in AIDS-free seroconverters and seropositives were similar, despite indeterminate differences in durations of infections. In the multivariate Cox regression analysis, baseline CD4%, the rate of change of CD4%, and baseline lymphocyte count were associated with AIDS-free survival time. Baseline CD4% had greater prognostic value than baseline CD4 cell count. Baseline CD8%, baseline CD8 count, their rates of change and their mean square errors were not independently significant in this analysis. These findings are important for clinicians monitoring HIV infection in an individual and for entry criteria and monitoring procedures in clinical trials. They also have implications for resource-poor settings; prognosis based on CD4% can be made with a flow cytometer without a full blood count.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1991

The risk of carcinoma in wire localization biopsies for mammographically detected clustered microcalcifications.

A total of 183 consecutive patients undergoing biopsies for unilateral microcalcifications concentrated in one or more segments of the breast in the absence of any palpable findings were analyzed to characterize their risk of cancer. Biopsy findings were benign in 86 patients (47%) and malignant in 97 (53%). Of the clinical and mammographic characteristics evaluated, an increasing number of linear microcalcifications, either without a dominant density (p = 0.014) or with a dominant density (p = 0.019) and the presence of heterogeneous microcalcifications (p = 0.055), were associated with a significantly increased risk of malignancy. Conversely a fibronodular parenchymal pattern (p = 0.008) was associated with a significantly decreased risk of malignancy. A high-risk group was identified, 95% (40/42) of whom had malignant biopsy findings, whose mammograms had more than 10 linear microcalcifications not associated with a dominant density (16/17) or at least one linear microcalcification associated with a dominant density (24/25). Conversely a low-risk group for cancer was identified, 88% (28/32) of whom had benign biopsy findings, whose mammograms had exclusively punctate microcalcifications within a fibronodular parenchymal milieu (26/30) or demonstrated some change in the configuration of the microcalcifications on the various mammographic views (10/10). For the remaining 109 patients there was an almost equal division between malignant and benign diagnoses (49% vs 51%).

Adenofibroma↗

PubMed1991

Survival with regional and distant metastases from cutaneous malignant melanoma.

The clinical course of 312 consecutive patients after initial presentation with metastatic melanoma, 165 of whom presented with regional metastases at cutaneous or subcutaneous, or both, nodal sites and 147 with metastases at distant sites, was reviewed. The five year survival rate for regional metastases was 43.4 per cent compared with a five year survival rate for distant metastases of 4.9 per cent (p less than 0.0001). Favorable prognostic variables for survival from first regional metastases included primary melanoma sites on the extremities compared with the head, neck and trunk (p = 0.043) and a disease-free interval of more than one year from primary surgical treatment to regional metastases (p = 0.0058). Favorable prognostic variables for survival from the first distant metastasis included a disease-free interval of more than one year from primary surgical treatment to distant metastases (p = 0.0092), the type of resection of metastatic disease (p = 0.00027) and the addition of systemic immunotherapy (p = 0.0011). Forty-nine patients with totally resectable distant metastases had a five year survival rate from the treatment of the initial metastasis of 13.1 per cent, whereas 33 patients having palliative resections had a five year survival rate of 7.5 per cent. All 165 patients who did not have resection for distant metastases died within five years. The results of our experience support therapeutic efforts to ablate both regional and distant metastases of malignant melanoma when feasible.

Adult↗