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Biomedical subjects

D F Yankelevitz

Publications and source records attributed to D F Yankelevitz.

At least 19 recordsLinked to original sources

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer.

PURPOSE: Preclinical studies suggest that treatment with a selective cyclo-oxygenase-2 (COX-2) inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with non-small-cell lung cancer (NSCLC) were preoperatively treated with celecoxib in combination with chemotherapy. End points were toxicity, response rates, and measurement of intratumoral levels of prostaglandin E2 (PGE2). METHODS: In this phase II trial, 29 patients with stages IB to IIIA NSCLC were treated with two preoperative cycles of paclitaxel and carboplatin, as well as daily celecoxib, followed by surgical resection. Levels of PGE2 in the primary tumors and adjacent normal lung tissue were compared in 17 study patients versus 13 controls, who received preoperative paclitaxel/carboplatin without celecoxib. RESULTS: All patients completed preoperative chemotherapy, and 26 completed preoperative celecoxib. The overall clinical response rate was 65% (48% with partial response; 17% with complete response). Grade 3 or 4 neutropenia was observed in 18 patients (62%). Twenty-eight patients were explored and underwent complete resection of their tumors. There were no complete pathologic responses, but seven patients (24%) had minimal residual microscopic disease. The addition of celecoxib to a regimen of paclitaxel and carboplatin abrogated the marked increase in levels of PGE2 detected in primary tumors after treatment with paclitaxel and carboplatin alone. CONCLUSION: In comparison with historically reported response rates, these data suggest that the addition of a selective COX-2 inhibitor may enhance the response to preoperative paclitaxel and carboplatin in patients with NSCLC. Moreover, treatment with celecoxib 400 mg twice daily was sufficient to normalize the increase in PGE2 levels found in NSCLC patients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.

Adult↗

Guidelines for the use of spiral computed tomography in screening for lung cancer.

Screening should be considered in lung cancer, more than any other cancer. Not only is the disease highly fatal, essentially incurable, when diagnosed on the prompting of symptoms and/or clinical signs, but its occurrence is also highly concentrated in identifiably high-risk persons. The degree of usefulness of computed tomography (CT)-based screening for lung cancer must be thought of in reference to a particular, presumably optimal, regimen of pursuing early stage diagnosis. This is an algorithm that begins with the initial test ("screening CT") and ends in either discontinuation of the diagnostic pursuit or in diagnosis of lung cancer. A carefully developed, extensively pilot tested and critically reviewed, updated protocol for CT-based screening for lung cancer is presented here. Its implementation is addressed, together with quality assurance. Finally, the associated curability rate for lung cancer is addressed in the light of what is known or can be surmised from evidence already available. However, recommendation for or against screening requires further information. Principally, the patients risk for lung cancer (in the near future) and the patients life expectancy (when spared of death from lung cancer). These two factors influence when, if ever, to begin screening, and if it is initiated, when to discontinue it. Finally, cost-effectiveness of the screening program should also be considered.

Humans↗

Early lung cancer action project: initial findings on repeat screenings.

BACKGROUND: The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. METHODS: A cohort of 1000 high-risk individuals was recruited for baseline and annual repeat CT screening. At last follow-up, a total of 1184 annual repeat screenings had been performed. A positive result from the screening test was defined as newly detected, one to six noncalcified pulmonary nodules with interim growth. The diagnostic workup of the individuals was guided by recommendations supplied by the ELCAP investigators to the collaborating clinicians. RESULTS: Of the 1184 repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30 cases, the individual died (of an unrelated cause) before diagnostic workup and the nodule(s) resolved in another 12 individuals. In the remaining 16 individuals, the absence of further growth was documented by repeat CT in 8 individuals and further growth was documented in the remaining 8 individuals. All eight individuals with further nodular growth underwent biopsy and malignancy was diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas (five of which were Stage IA and one of which was Stage IIIA) and the one small cell carcinoma was found to be of limited stage. The median size dimension of these malignancies was 8 mm. In another two subjects, symptoms prompted the interim diagnosis of lung carcinoma. Neither of these malignancies was nodule-associated but rather were endobronchial; one was a Stage IIB nonsmall cell carcinoma and the other was a small cell carcinoma of limited stage. CONCLUSIONS: False-positive screening test results are uncommon and usually manageable without biopsy; compared with no screening, such screenings permit diagnosis at substantially earlier and thus more curable stages. Annual repetition of CT screening is sufficient to minimize symptom-prompted interim diagnoses of nodule-associated malignancies.

Aged↗

Smoking cessation following CT screening for early detection of lung cancer.

BACKGROUND: This study was conducted to assess the impact of lung cancer screening participation on smoking cessation. METHODS: Individuals (n = 134) who reported active smoking at the time of enrollment in our Early Lung Cancer Action Program (ELCAP) completed a brief, follow-up telephone interview assessing any changes in smoking patterns following lung cancer screening. Using logistic regression, we estimated the probability of decreasing or quitting smoking using each enrollee's background information and computed tomography (CT) scan results. RESULTS: Most survey respondents (74%) agreed that participation in the ELCAP increased their motivation for quitting smoking. In terms of self-reported changes in smoking behavior, 31 (23%) reported that they had quit and 35 (27%) decreased their smoking patterns. Several significant covariates of smoking cessation were identified: perceived benefit of quitting (OR 4.02), cancer anxiety (OR 2.49), younger age (OR 2.47), and abnormal CT finding (1.97). CONCLUSIONS: Our analyses suggest that low-dose helical CT scanning may serve as a strong catalyst for smoking cessation and that delivery of effective smoking cessation interventions along with CT scanning represents a potential opportunity to increase the overall cancer prevention benefit of lung cancer screening.

Aged↗

Early lung cancer action project: annual screening using single-slice helical CT.

The advent of helical CT imaging held promise for the early diagnosis, and thereby, for enhanced curability of lung cancer--a highly fatal disease. In 1993, the Early Lung Cancer Action Project (ELCAP) was initiated and experimentally screened a cohort of 1,000 high-risk persons. Here we summarize the results of the baseline and annual repeat CT screening of these 1,000 subjects. CT-based screening (compared to traditional radiology) was clearly shown to enhance the detection of lung cancer at earlier and more curable stages. A discussion follows of the meaning of the results and possible future screening protocols.

Aged↗

Early lung cancer action project: a summary of the findings on baseline screening.

PURPOSE: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low radiation dose computed tomography (low-dose CT) in persons at high-risk for lung cancer. METHODS: Since starting in 1993, the ELCAP has enrolled 1,000 asymptomatic persons, 60 years of age or older, with at least 10 pack-years (1 pack per day for 10 years, or 2 packs per day for 5 years) of cigarette smoking, no prior cancer, and medically fit to undergo thoracic surgery. After a structured interview and informed consent, baseline chest radiographs and low-dose CT were obtained on each subject. The diagnostic work-up of screen-detected noncalcified pulmonary nodules (NCN) was guided by ELCAP recommendations which included short-term high-resolution CT follow-up for the smallest nodules. Baseline RESULTS: On low-dose CT at baseline compared to chest radiography, NCN were detected three times as commonly (23% versus 7%), malignancies four times as commonly (2.7% versus 0.7%), and stage I malignancies six times as commonly (2.3% versus 0.4%). Of the 27 CT-detected cancers, 96% (26/27) were resectable; 85% (23/27) were stage I, and 83% (19 of the 23 stage I) were not seen on chest radiography. Following the ELCAP recommendations, biopsies were performed on 28 of the 233 subjects with NCN; 27 had a malignant and one a benign NCN. Another three individuals underwent biopsy outside of the ELCAP recommendations; all had benign NCNS: No one had thoracotomy for a benign nodule. CONCLUSION: Baseline CT screening for lung cancer provides for detecting the disease at earlier and presumably more commonly curable stages in a cost-effective manner.

Clinical Trials as Topic↗

Special techniques in transthoracic needle biopsy of pulmonary nodules.

We believe that each aspect of the performance of TNB needs to be considered carefully. Meticulous attention to detail allows any nodule in the chest to successfully undergo biopsy. There are techniques of needle tip repositioning that can be quite helpful for obtaining diagnostic material from lung lesions, particularly small nodules. A strong working relationship with pathologists experienced in lung cytology is a vital element of any successful biopsy program. Techniques available to the pathologist allow for quick and decisive determination of the adequacy of the aspirated specimen and help guide the radiologist performing the procedure. Newer cytopathologic techniques help the pathologist make more complex diagnoses from the aspirated material. Finally, techniques used to minimize complications should be considered by the operator before the performance of the biopsy.

Biopsy, Needle↗

Small solitary pulmonary nodules.

We now are detecting an increasing number of SPN that are difficult to diagnose. Many of the techniques we traditionally have relied on were developed when the average size of detected nodules was larger, and these techniques are of limited diagnostic usefulness for small nodules. In the past, recognition of the need for noninvasive differentiation between benign and malignant nodules led to the development of many useful diagnostic techniques. The ever increasing number of small nodules now being detected will stimulate new approaches. In the future, as in the past, many of these will be based on previously developed concepts. Because a majority of these small nodules will be benign, it will be important to develop reliable methods of determining which patients need further evaluation both from a patient management and cost-effectiveness perspective. Criteria will need to be developed based on the initial CT appearance of the nodule, clinical information about the patient, and subsequent CT using the latest decision analytic techniques and databases. Finally, increased interest in predicting the aggressiveness of a lung cancer, once it has been discovered, could lead to further changes in staging criteria.

Humans↗

CT screening for lung cancer.

Recommendations against screening for lung cancer were based on the lack of a reduction in mortality of the screened group as compared with the control group in randomized control trials. These results were interpreted as showing that early detection of lung cancer as a result of screening did not decrease the mortality rate compared with detection after presentation of symptoms for the populations being screened. Evidence, however, shows that earlier-stage intervention leads to substantially higher rates of survival. Screening, therefore, is an effective means to prevent deaths from this otherwise fatal disease. This article discusses the evidence of both CT and chest radiograph screening.

Humans↗

Comparison of biopsy techniques in assessment of solitary pulmonary nodules.

A wide variety of diagnostic tests are available to evaluate solitary pulmonary nodules, ranging from noninvasive to invasive. Given the virulence of lung cancer, those techniques that can provide cytological and pathological information are often chosen. However, the choice of which procedure to perform is complicated by numerous factors, including the sensitivity and specificity of the test, as well as the prevalence of disease. Additional considerations also include complications, availability and expertise in performing procedures, and overall cost of the diagnostic algorithm. Rather than make specific recommendations for diagnostic workup, it is more appropriate to consider that this will vary from institution to institution based on the above factors.

Algorithms↗

The radiologic appearance of solitary pulmonary nodules and their cytologic-histologic correlation.

In this article, we review the various causes of solitary pulmonary nodules. Based on the underlying histology, we attempt to account for the radiologic pattern associated with each. This includes features related to density, edge characteristics, and texture. Similarly, the radiologic appearance of the nodule can be helpful to the cytologist when interpreting cytological samples obtained through image guidance.

Cytodiagnosis↗

Screening for lung cancer.

Screening for lung cancer has remained controversial since the completion, more than two decades ago, of the three large randomized controlled trials, sponsored by the National Cancer Institute, which led to the recommendation against screening by major medical organizations. Details of the controversy are given, which include concerns about the study design, implementation, and analysis. New evidence about the potential benefit of screening with chest radiography that has emerged since the completion of those trials is reviewed, as well as the results of studies of CT screening for lung cancer.

Humans↗

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.

Adolescent↗

Small pulmonary nodules: volumetrically determined growth rates based on CT evaluation.

PURPOSE: To determine the accuracy of high-resolution computed tomographic (CT) volumetric measurements of small pulmonary nodules to assess growth and malignancy status. MATERIALS AND METHODS: The accuracy of three-dimensional (3D) image extraction and isotropic resampling techniques was assessed by performing three experiments. The first experiment measured volumes in spherical synthetic nodules of two diameters (3.20 and 3.96 mm), the second measured deformable silicone synthetic nodules prior to and after their shape had been altered markedly, and the third measured nodules of various shapes and sizes. Three-dimensional techniques were used to assess growth in 13 patients for whom the final diagnosis was known and whose initial nodule diameters were less than 10 mm. By using the exponential growth model and the calculated nodule volume at two points in time, the doubling time for each subject was calculated. RESULTS: The three synthetic nodule studies revealed that the volume could be measured accurately to within +/-3%. All five malignant nodules grew, and all had doubling times less than 177 days. Some malignant nodules had asymmetric patterns of growth identified by using the 3D techniques but not the two-dimensional methods. All eight benign nodules had doubling times of 396 days or greater or showed a decrease in volume. CONCLUSION: CT volumetric measurements are highly accurate for determining volume and are useful in assessing growth of small nodules and calculating their doubling times.

Aged↗

Optimization of combined CT pulmonary angiography with lower extremity CT venography.

OBJECTIVE: We wanted to determine the time delay for maximum enhancement of the deep venous system of the lower extremities after standard CT pulmonary angiography. SUBJECTS AND METHODS: In 20 patients who had undergone standard CT pulmonary angiography, we measured arterial and venous enhancement at the level of the greater trochanter. These measurements were obtained at 30-sec intervals immediately after completion of CT pulmonary angiography. Ten measurements were obtained in 5 min. Time-density curves were plotted. RESULTS: We found that the median and average peak venous enhancements were 92 and 95 H, respectively. Time to peak enhancement was variable. Because of the broad shape of the venous time-density curve, near peak enhancement could be achieved in most patients at 2 min after CT pulmonary angiography. CONCLUSION: CT of the deep venous system of the lower extremities after standard CT pulmonary angiography, performed with appropriate timing considerations, allows near maximal enhancement of the venous system in most patients without altering the optimum CT pulmonary angiography protocol.

Female↗

Early Lung Cancer Action Project: overall design and findings from baseline screening.

BACKGROUND: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer. We report the baseline experience. METHODS: ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery. After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant. The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules. FINDINGS: Non-calcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography. Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]), respectively. Of the 27 CT-detected cancers, 26 were resectable. Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant non-calcified nodules and one had a benign nodule. Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules. No participant had thoracotomy for a benign nodule. INTERPRETATION: Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.

Aged↗