Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy.

BACKGROUND: The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. PURPOSE: This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS: From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. RESULTS: Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS AND IMPLICATIONS: The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.

Stomach and colorectal cancers in Puerto Rican-born residents of New York City.

Colorectal cancer incidence and mortality rates for Puerto Rican-born residents in New York City (PR-NYC) for 1975-79 were about two times those for Puerto Ricans living in Puerto Rico (PR-PR) and one-half to almost two-thirds those for other whites in New York City. From 1958 to 1979, colon cancer mortality rates for PR-NYC increased dramatically (i.e., 212% in males and 54% in females), whereas in PR-PR, male rates increased only slightly and female rates remained constant. For stomach cancer, incidence rates for male and female PR-NYC were slightly, but not significantly, higher than those for male and female PR-PR. In contrast, stomach cancer mortality rates for PR-NYC were lower than those for PR-PR throughout the survey period, and mortality decreased substantially in all racial-ethnic groups in New York City and Puerto Rico from 1958 to 1979. Results of this study indicated that the changes in colorectal and stomach cancer incidence and mortality in Puerto Rican-born residents after migration to New York City, although not as dramatic as in migrants from Japan and Eastern Europe, were comparable to those observed for Hispanic migrants to New Mexico and Los Angeles.

Hydralazine and breast cancer.

Hydralazine (CAS: 86-54-4; 1-hydrazinonaphthalazine) is a well-established antihypertensive agent. There are no conclusive data on the drug as a human carcinogen, but one of its metabolites, hydrazine (CAS: 302-01-2), has been shown to be carcinogenic in rats and mice. To assess the relationship of hydralazine to human breast cancer, 3,419 women with breast cancer and 3,219 hospital control subjects were studied. Data were obtained by interview in hospitals in the United States and Canada. A total of 1.4% of the cases and 1.2% of the controls had used hydralazine. Compared with never use, the relative risk (RR) estimate for hydralazine that was first used at least 18 months before admission was 0.9 [95% confidence interval (CI), 0.5-1.7] after risk factors for breast cancer and the use of other antihypertensive drugs and diuretics were taken into account by multivariate analysis. The RR estimate for hydralazine use lasting at least 1 year was 0.9 (95% CI, 0.5-1.7). RR estimates for longer durations of use (up to 5 or more yr), and for use within strata of risk factors for breast cancer, were close to 1.0. The results suggest that hydralazine does not increase the risk of breast cancer in humans in the short term. Whether the risk is increased after latent intervals of many years could not be evaluated.

Second primary cancers following treatment of Hodgkin's disease.

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was conducted. This report describes 2,591 patients with HD diagnosed in 1940-75 and presents an analysis of follow-up findings through 1978. Seventy-four second primary cancers (excluding basal cell and squamous cell cancers of the skin and in situ carcinomas of the cervix uteri) were observed 1 year or more after diagnosis of HD, including 21 leukemias. Twenty leukemias occurred after chemotherapy. The relative risk (RR) of leukemia after intensive chemotherapy with or without radiotherapy was 136 relative to general population incidence rates. In the subgroup with both intensive chemotherapy and intensive radiotherapy, the RR of leukemia was 125. Both RR estimates differed significantly from unity. The RR of cancers other than leukemia 10 years or more after intensive radiotherapy relative to no intensive therapy was 19.5 (95% confidence limits: 4.8-80).

Lack of an elevated risk of malignant melanoma in relation to oral contraceptive use.

Epidemiologic and laboratory data suggest an effect of oral contraceptives (OC) on the risk of malignant melanoma. This relationship was explored in a hospital-based case-control study of 160 women with malignant melanoma and 640 matched controls, all of whom were white and 20-59 years of age. A total of 63 cases (39%) had used OC compared with 270 controls (42%), yielding a relative risk estimate of 0.9 (95% confidence interval: 0.6-1.3). When a number of potential confounding factors were simultaneously controlled, the relative risk estimate was 0.8 (0.5-1.3). For use that lasted 5 or more years the estimate was 0.9 (0.5-1.6). The level of tumor invasion was not related to OC use. The evidence from this study suggests that OC, even when used for 5 or more years, do not increase the risk of malignant melanoma.

Carotid body tumors in humans: genetics and epidemiology.

Genetic factors in the etiology of carotid body tumors (CBT) were sought in a medical record review of 222 histologically diagnosed cases at 12 U.S. medical centers. Patients in the series, which had a marked female predominance (146 females:76 males), usually developed tumors between the fourth and seventh decades of life (mean, 44.7 yr). In 16 patients who also had other extra-adrenal paragangliomas, suggesting a multiple primary tumor syndrome, CBT were diagnosed significantly earlier (mean, 35.4 yr; P less than 0.01). The occurrence of thyroid cancer in 5 other patients appeared to be excessive. Familial CBT was recognized in 16 patients from 13 affected families, including 9 newly ascertained kindreds. Compared with non-familial lesions, familial CBT tended to develop bilaterally (38% vs. 8% unilaterally) and at slightly earlier ages (41.6 vs. 44.9 yr). CBT was reported to occur in an autosomal dominant pattern in some families and within sibships in others; relatives were not examined for confirmation. The familial findings are generally consistent with a two-step mutation model of the development of hereditary and nonhereditary CBT; apparent deviations from the model might be clarified with additional data on this rare neoplasm.

Leukemia following treatment of germ cell tumors in men.

We investigated the incidence of leukemia occurring subsequent to the treatment of germ cell tumors in men at our institution over a 30-year interval and found four patients with acute nonlymphocytic leukemia (ANLL) and one patient with chronic myelomonocytic leukemia. The relative risk (observed/expected cases) estimates for the development of leukemia ranged from 13.7 (P = .0005) in the total population to 50.1 (P = .0001) in the group treated with cytotoxic agents alone. All three patients with ANLL treated with contemporary antileukemic therapy had complete responses, with survivals of 7, 29, and 133 + months. In a review of the literature, 14 additional cases of germ cell tumors were found in which the men subsequently developed leukemia. It is concluded that leukemia following germ cell tumors is increased in incidence and is likely to be treatment induced. Complete responses and long-term survival are possible in secondary leukemia and aggressive antileukemic therapy should be given.

A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix.

PURPOSE: Previous trials of topical trans-retinoic acid treatment of cervical intraepithelial neoplasia (CIN) grades 2 and 3 led to a statistically significant regression of CIN 2, but not CIN 3. We tested N-(4-hydroxyphenyl)retinamide (4-HPR), a promising oral retinoid that has been shown to induce apoptosis through nonretinoic receptor acid-mediated pathways, for its toxicity and efficacy against CIN 2/3. EXPERIMENTAL DESIGN: In a blinded randomized trial, 4-HPR at 200 mg/day for 6 months (with a 3-day/month drug holiday) was compared with placebo in patients with biopsy-proven CIN-2/3 [high-grade squamous intraepithelial lesions (HGSILs)]. Patients were treated with placebo or 4-HPR for 6 months, biopsied, and then followed for an additional 6 months. At the 12-month end point, they underwent either loop excision if a histological lesion was present or a biopsy from the original area of the lesion if no lesion was present. RESULTS: An interim analysis of blinded data showed a significantly worse prognosis at 12 months for one group. When the code was broken because of the poorer outcomes, we discovered that the 4-HPR treatment arm was performing more poorly than was the placebo at 6 and 12 months (25 versus 44% response rates at 6 months; 14 versus 50% at 12 months). Toxicity was not significant in either arm. CONCLUSIONS: 4-HPR at 200 mg/day with a 3-day/month drug holiday is not active compared with placebo in the treatment of HGSIL. Because 4-HPR is active in the laboratory, the lack of effect in our trial may indicate that higher doses are needed in patients to achieve comparable results.

Cervical human papillomavirus infection and intraepithelial neoplasia: a review.

Cervical human papillomavirus (HPV) infections and intraepithelial neoplasias are precursors to cervical cancer, the second most common cancer in women worldwide. HPV satisfies the epidemiologic criteria for causality; the role of other cofactors is under study. Natural history studies show that most low-grade lesions (productive HPV infections) regress or persist, whereas high-grade lesions (those with integrated HPV DNA) progress. Immunobiologic studies demonstrate that infection peaks in the early 20s, leading to a 10- to 20-year period of persistent infection, before finally progressing to a preinvasive or invasive lesion. Papanicolaou (Pap) screening has lowered the morbidity and mortality from cervical cancer in every country in which screening programs have been introduced. The diagnostic strategy for an abnormal Pap smear includes colposcopy; the role of HPV DNA testing in screening or diagnosis remains unclear. Patients are treated with cervical ablation, cone biopsy, or chemopreventive agents. Efforts to strengthen screening and prevention, as well as new directions for research, are needed.

Declining FEV1 and chronic productive cough in cigarette smokers: a 25-year prospective study of lung cancer incidence in Tecumseh, Michigan.

A community-based study has been reviewed to assess whether impaired forced expiratory volume in 1 s (FEV1) and/or the symptoms of chronic cough and sputum production predict the incidence of lung cancer, after controlling for age, sex, cigarette smoking history, and the dietary intake of carotenoids and retinoids. A cohort of 2099 women and 1857 men, 25 years of age or older, were first examined from 1962 to 1965. As of 1987, there were 60 validated lung cancers diagnosed in men (1.83 per 1000 person-years) and 17 in women (0.39 per 1000 person-years). The incidence density of lung cancer in current smokers at baseline, when compared with never smokers, was increased 5.34 (95% confidence interval, 1.74, 16.38) times in women and 4.11 (95% confidence interval, 1.63, 10.34) times in men. The risk of lung cancer increased in women and men in relation to the average daily intensity of exposure in current smokers and the duration of smoking history (< 20 years, > or = 20 years) in current and ex-smokers. When stratified by cigarette smoking intensity, subjects with chronic cough and phlegm experienced a future risk of lung cancer that was more than 3 times higher than that in the nonsymptomatic subgroup. Among the smoking women and men at entry, those in the lowest quartile of the percent predicted FEV1, after controlling for the average number of cigarettes smoked per day, experienced a risk of lung cancer that was 2.7 times that of subjects in the highest quartile. With each 10% decrease in percent predicted FEV1, the risk of lung cancer increased 1.17 times (0.96, 1.42), after controlling for age, sex, and cigarette smoking intensity at baseline. The average annual decline in FEV1 as estimated between 1962 and 1965 and 1967 and 1969 was a significant independent predictor of future lung cancer incidence after controlling for cigarette smoking history; the slope of the regression line indicated that with each decline in FEV1 of 100 ml/year, lung cancer incidence density increased 1.16 per 1000 person-years (95% confidence interval, 0.30, 2.01). Controlling for potential confounding by quartile distribution of calorie-adjusted dietary intake of vitamin A, beta-carotene, cholesterol, and fat did not weaken or alter the fundamental relationship with impaired pulmonary function. Rapidly declining ventilatory function in conjunction with persistent symptoms of chronic bronchitis in current smokers is predictive of the increased risk of lung cancer and correlates with cumulative levels of exposure to cigarette smoking.(ABSTRACT TRUNCATED AT 400 WORDS)

The natural history of cervical intraepithelial neoplasia: an argument for intermediate endpoint biomarkers.

Cervical cancer is the second most common malignancy in women worldwide and remains a significant health problem for women, especially minority women in the United States. Despite morbid and costly treatment with whole pelvic radiotherapy, radical surgery, and chemotherapy, the overall survival remains 40%. While the epidemiological risk factors are well known, little is known of the pathobiology of cervical carcinogenesis. Prevention of cervical cancer and its precursors is an important objective. New strategies, both clinical and laboratory based, are desperately needed. Cellular and molecular characteristics of the pathobiology of cervical cancer and its precursors need to be quantified, thereby providing insights into the multistep process of cervical carcinogenesis, identifying those precancerous lesions at high risk for progression to invasion, providing potential targets for intervention, and providing intermediate end point biomarkers for chemopreventive therapies. The premise for this strategy in cervical cancer prevention is that squamous cancers of the female genital tract have a well defined preinvasive stage, and that carcinogenesis is a multistep genetic process which involves increasing dysregulation of proliferation and differentiation as lesions progress from normal to human papillomavirus infected tissue to cervical intraepithelial neoplasia to cancer.

Alcohol consumption and the risk of breast cancer: a report from the Tecumseh Community Health Study.

The relationship between prior alcohol consumption and the risk of breast cancer was studied in 1954 women in the Tecumseh Community Health Study (TCHS) who entered the cohort in 1959-1960 and were followed potentially for 28 years. The mean alcohol consumption at baseline was 0.89 (SD 2.2) oz/week for premenopausal women and 0.85 (SD 2.2) oz/week for postmenopausal women. Only 25% of the cohort consumed more than 0.5 oz of ethanol/week or about 1.6 g/day. The adjusted relative risks (RRs) for breast cancer associated with the use of ethanol vs never drinking were 0.93 (95% CI, 0.40-2.18) for ex-drinkers, 1.08 (95% CI, 0.64-1.82) for 0- less than 1 drink/day, 1.23 (95% CI, 0.49-3.10) for 1- less than 2 drinks/day and 1.12 (95% CI, 0.25-5.01) for greater than or equal to 2 drinks/day. There were only 37 subjects in the group at the highest level of consumption (greater than or equal to 2 drinks/day). There was no significant interaction between alcohol and the period of onset of breast cancer (premenopausal or postmenopausal). In the TCHS, alcohol consumption generally at levels not exceeding 2 drinks/day, was not significantly associated with an increased risk of breast cancer. Although we have found little excess risk associated with alcohol consumption, the wide confidence intervals summarized above are not inconsistent with previously published reports that have suggested a modest positive association.

Potential selection bias in a community-based study of PSA levels in African-American men.

The first phase of the Flint Men's Health Study (FMHS) in Michigan was a community-based epidemiologic study of prostate cancer and benign prostatic hyperplasia (BPH) in African-Americans aged 40 to 79 years. An objective of the FMHS was to determine age-specified prostate specific antigen (PSA) reference ranges in a random population sample of African-American men without clinically evident prostate cancer. The FMHS study protocol included an initial in-home epidemiologic interview followed by PSA testing and a urologic examination of eligible subjects. Since the participation rate in the PSA phase of the study was under 60%, it was important to determine whether selectivity in participation biased the FMHS results for age-specific PSA distributions. Logistic regression analyses were used to investigate selectivity in the sample of subjects who participated in the PSA testing and urologic examination. Younger men, with current urologic symptoms, and with a family history of prostate cancer were more likely to participate in the PSA testing and urologic examination. Linear regression analysis indicated that greater participation by African-American men without clinically evident prostate cancer but with obstructive or irritative lower urinary tract symptoms or a family history of prostate cancer did not bias the estimated age-specific reference ranges for total PSA concentrations and free-to-total PSA ratios.

Epithelial ovarian cancer and coffee drinking.

A recent report from a case-control study in Greece suggested that coffee consumption is related to an increase in the risk of ovarian cancer. This hypothesis was examined in a hospital-based case-control study in the US. Information on coffee drinking and other factors was obtained from 290 incident cases of epithelial ovarian cancer and compared with that of 580 controls with non-malignant conditions of acute onset and 476 controls with cancer of other sites. Adjustment was made for the potential confounding effects of several factors, including the major known risk factors for ovarian cancer. The estimated relative risk for drinking five or more cups of coffee per day, relative to none, was 1.1 (95% confidence interval, 0.6-2.0) using the controls with non-malignant conditions and 1.0 (0.5-1.8) using the controls with cancer. The estimates for drinking less than five cups per day were greater than 1.0, but this could have been due to chance. The consumption of decaffeinated coffee and tea also appeared to have no influence on risk. The evidence from this study suggests that, if coffee drinking increases the risk of ovarian cancer, the effect is small.

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Epidemiology of breast carcinoma: Age, menstrual status, and exogenous hormone usage in patients with lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) of the breast is a neoplastic condition associated with premenopausal women and it is largely for this reason that LCIS has been considered to be an estrogen-dependent lesion. In this report we present the results of a study of age at diagnosis, menstrual status, and exogenous hormone usage in 59 women with LCIS and in 190 patients with duct carcinoma. When LCIS was associated with duct carcinoma, 46% of patients were postmenopausal and in the group that also had infiltrating lobular carcinoma 71% were postmenopausal. Nine of 39 (23%) patients whose only carcinoma was LCIS were postmenopausal, 56% were premenopausal and 21% were menopausal. Seven of the nine postmenopausal women had never used a hormone-containing medication. In a comparison group with only duct carcinoma, 59.4% were postmenopausal and 35.2% had taken a hormone preparation. The high proportion of postmenopausal patients with LCIS leaves considerable doubt as to whether all lesions termed LCIS are equally dependent on estrogens at all stages in their evolution. We found no evidence to link LCIS with exogenous hormone usage in postmenopausal women. Prospective studies of hormone levels in patients with LCIS and in their relatives may provide an explanation for persistence of the lesion in postmenopausal women and could aid in identifying women at risk of developing invasive carcinoma.

Breast cancer risk in relation to early oral contraceptive use.

It has been suggested that the risk of breast cancer is increased by oral contraceptive use before the first birth, or by use before age 25, particularly if certain formulations are used. These hypotheses were evaluated in a hospital-based case-control study. A total of 521 patients under age 45 with breast cancer were compared with 521 controls matched for age, time of interview, and geographic area. Oral contraceptive use before the first birth was reported by 155 patients and 137 controls. With allowance for confounding by multivariate analysis, the estimated relative risk was 1.0 (95% confidence interval, 0.6-1.5). The estimate was 1.0 (0.2-3.9) for any use among nulliparous women and 0.6 (0.3-1.3) for use before the first birth among parous women. Use before age 25 was reported by 145 patients and 141 controls, and the multivariate relative risk estimate was 1.0 (0.7-1.6); the results were similar when use of specific formulations was examined. For oral contraceptive use before either the first birth or age 25, the relative risk estimates were compatible with 1.0 for use of five or more years' duration or an interval since first use of at least 15 years. There was also no evidence of an increased risk in any subgroup including those at increased underlying risk because of factors such as a family history of breast cancer or a history of cystic breast disease. The findings suggest that, up to age 45, the risk of breast cancer is not influenced by the use of oral contraceptives before the first birth or before age 25 even if the use lasted for five or more years.

Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta-analysis.

OBJECTIVE: To quantify by meta-analysis the performance of colposcopy to set a standard against which new technologies can be compared. DATA SOURCES: MEDLINE was searched for articles on colposcopy for diagnosis of squamous intraepithelial lesions (SIL). The search selected articles from 1960 to 1996 combining the key word "colposcopy" with key words "diagnosis," "positive predictive value," "negative predictive value," "likelihood ratio," and "receiver operating characteristic (ROC) curve." METHODS OF STUDY SELECTION: Articles were selected if the authors studied a population of patients with abnormal screening Papanicolaou smears and presented raw data showing for each cervical lesion type the number of patients judged positive and negative by colposcopic impression versus the standard of colposcopic biopsy results. Nine of 86 studies met these criteria. TABULATION, INTEGRATION, AND RESULTS: Biopsies had been categorized as normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, carcinoma in situ, and invasive cancer; we recalculated performance measures using the Bethesda system. Overall sensitivity, specificity, likelihood ratios, ROC curves, and the corresponding areas under the curves were calculated. The average weighted sensitivity of diagnostic colposcopy for the threshold normal compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL, cancer) was 96% and the average weighted specificity 48%. For the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer, average weighted sensitivity was 85% and average weighted specificity 69%. Likelihood ratios generated small but important changes in probability for distinguishing normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the ROC curve were 0.80 for the threshold normal cervix compared with all abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer. CONCLUSION: Colposcopy compares favorably with other medical diagnostic tests in terms of sensitivity, specificity, and area under the ROC curve. New diagnostic methods for the cervix can be compared with colposcopy using these quantified values.

Screening for squamous intraepithelial lesions with fluorescence spectroscopy.

OBJECTIVE: To evaluate the accuracy of fluorescence spectroscopy in screening for squamous intraepithelial lesions (SILs) and to compare its performance with that of Papanicolaou smear screening, colposcopy, cervicoscopy, cervicography, and human papillomavirus (HPV) testing. DATA SOURCES: Receiver operating characteristic (ROC) curve analysis was used to analyze performance by fluorescence spectroscopy (primary data) and other methods (secondary data). METHODS OF STUDY SELECTION: In our search, 275 articles were identified in MEDLINE (1966-1996). Articles were included if the investigators had studied a population in whom low disease prevalence was expected; used either Papanicolaou smear screening and colposcopy or colposcopically directed biopsy as a standard against which the screening technique was measured, and included enough data for recalculation of reported sensitivities and specificities. TABULATION, INTEGRATION, AND RESULTS: Receiver operating characteristic curves for fluorescence spectroscopy were calculated using a Bayesian algorithm, and ROC curves for the other screening methods were constructed using metaanalytic techniques. Areas under the ROC curves and Q points were calculated. Screening colposcopy had the highest area under the curve (0.95), followed by screening cervicography (0.90), HPV testing (0.88), cervicoscopy (0.85), fluorescence spectroscopy (0.76), and Papanicolaou smear screening (0.70). CONCLUSION: In terms of screening for SILs, fluorescence spectroscopy performed better than the standard technique, Papanicolaou smear screening, and less well than screening colposcopy, cervicography, HPV testing, and cervicoscopy. The promise of this research technique warrants further investigation.

En bloc resection of primary melanoma with regional lymph node dissection.

En bloc resection of the primary melanoma with the regional lymph node drainage basin as a method of controlling disease within the area was used in 281 patients with stage I or II melanoma arising on the extremities (proximal to wrist or ankle) or on the trunk from 1954 through 1964. The en bloc operation was performed in 212 patients with a five-year cure of 73.5% (156 of 212). Seventy-six percent had histologically negative nodes. Only 2% developed regional recurrence. Sixty-nine patients had a discontinuous dissection. The five-year cure was comparable: 68% (47 of 69). The incidence of histologically negative nodes was similar (77%), but the regional recurrence rate was 14%. This difference is significant at P < .01. The incontinuity or en bloc procedure appears highly effective for its designed purpose.