Chelation Clinics

REFERENCES

1 Levin ML, Tockman MS, Frost JK, Ball WC Jr. Lung cancer mortality in males screened by chest x-ray and cytologic sputum examination: a preliminary report. Recent Results in Cancer Research 1982; 82:138-46 2 Weiss W. Survivorship among men with bronchogenic carcinoma: three studies in populations screened every six months. Arch Environ Health 1971; 22:168-73 3 Weiss W, Boueot KR, Seidman H. The Philadelphia pulmonary neoplasm research project. Clin Chest Med 1982; 3:243-56 4 Brett GZ. Earlier diagnosis and survival in lung cancer. Br Med J 1969; 4:260-62 5 Sanderson D, Fontana R. Results of the Mayo lung project: an interim report. Recent Results in Cancer Research 1982; 82:179-86 6 Woolner LB, Fontana RS, Cortese DA, Sanderson DR, Bernatz PE, Payne WS, et al. Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10year period. Mayo Clin Proc 1984; 59:453-66 7 Auerbach 0, Stout A~ Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Eng) J Med 1961; 265:253-67 8 Miller AB, ed. Screening in Cancer. A report of a VICC International Workshop, Toronto, Canada, April 24-27, 1978, VICC Technical Report Series, Vol. 40. Geneva: International V nion Against Cancer, 1978; 261 9 Boucot KR, Weiss W. Is curable lung cancer detected by semiannual screening? JAMA 1973; 224:1361-65

risk, we have an incidence rate of 16 per 1,()()() person years for new primary second lung cancers after complete resection of the first. Five of the nine second primary cancers were resectable, and two of the five men treated by a second resection are alive and free of carcinoma six years and three years following resection of their second cancers. We find that very impressive. However, we agree with Dr. Weiss and with the consensus of the VICC International Workshop on screening in cancer;" in which he participated, that the basic index of screening efficiency should be population mortality, not case survival rate. We have reported the mortality rate from lung cancer in our population, but do not have a comparable population of unscreened, cigarette-smoking men with which they can be compared. There are other statistical approaches to solve this dilemma. The most promising, we believe, is through mathematical modeling based on the kind of precise, hard data available to us from the New York Lung Cancer Screening Program. We are presently engaged in deriving such a model from our data, and hope to use that model to show the effects of radiographic screening at various different frequencies, for populations that receive treatment of varying efficacy. It is our hope that we will have Dr. Weiss' critical comments on that effort when it is ready for formal presentation.

Myron R. Melamed, M.D.; Betty]. Flehinger, Ph.D., Memorial Sloan-Kettering Cancer Center, New York and IBM Thomas] Watson Research Center, Yorktown Hts, New York Reprint requests: Dr. Melamed. 1275 York Avenue, New York City

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To the Editor: Dr. Weiss participated in one of the first systematic studies of periodic screening as a potential means of controlling lung cancer, the Philadelphia Pulmonary Neoplasm Research project. I His reports of that work have become a classic source of reference. We thank him for his kind comments on our own study. We agree with Dr. Weiss that rigorous statistical proofof the value of periodic radiographic screening is lacking. We would strongly support a study to obtain that proof if we believed it possible to deny chest x-ray films to a randomized, high-risk "control" population with their informed consent. In the absence of irrefutable proof, we note the following softer evidence of value in periodic screening: a shift to earlier stage disease at diagnosis, an increase in the proportion of cases that are resectable, and better survival in the screened compared to the general population. We certainly see no justification for a change from the present medical practice of recommending annual chest x-ray examinations for asymptomatic, high-risk individuals. A decision to do otherwise, as we have noted, 2 is a decision not to treat lung cancer for cure since the symptomatic patient is essentially incurable. The proportion of early-stage lung cancer detected in our population, the percentage of cases resectable, and the length of survival all are greater than in the three early studies referred to by Dr. Weiss. Operative mortality today for treatment of lung cancer by lobectomy at Memorial Hospital is 2 percent," well below the 10-20 percent mortality of lung cancer surgery 20 years ago reported by Dr. Weiss.· Thus, we are seeing better radiographic detection and better treatment today than was the case 20 years ago. Patients who have had one lung cancer are at higher risk of another, as Dr. Weiss notes. In our population the risk of a new, second lung cancer following complete resection of a first is about fivefold the initial risk of lung cancer for the entire population. There were 12 men with multiple lung cancers among the 291 who have developed the disease at this writing. Three had two synchronous cancers. Nine of the 166 men who were treated by complete resection of their first cancer have since developed a second primary lung cancer (metachronous cancers). Based on a calculation of time at

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REFERENCES

Boucot KR, Cooper DA, Weiss W The Philadelphia pulmonary neoplasm research project: an interim report. Ann Intern Med 1961; 54:363-78 2 Melamed MR, Flehinger BJ. Screening for lung cancer (editorial). Chest 1984; 86:2-3 3 Nagasaki F, Flehinger BJ, Martini N. Complications of surgery in the treatment of carcinoma of the lung. Chest 1982; 82:25-9 4 Weiss W Problems in screening for lung cancer. In: Miller AB, ed, Screening in cancer. A Report of V.I.C.C. International Workshop, Toronto, Canada. April 24-27, 1978

Chelation Clinics To the Editor: There is more to the controversy regarding chelation therapy with disodium EDTA for the treatment of atherosclerosis than was presented in the editorial in Chest (1984; 86:157-58). Not only is efficacy unproven, but there is a report of a study done more than 20 years ago indicating that this form of treatment does not work. Kitchell et all at Presbyterian Hospital, Philadelphia, reported their observations in ten patients after four years of treatment and in 28 patients after one and one-halfto three years of chelation therapy: . . . after three months of treatment, 66 percent of these 38 patients exhibited improved anginal patterns (their own impressions and measured exercise tolerance) and 40 percent showed improved electrocardiographic patterns; none of these effects was lasting. At the time of this report, 12 of the 38 were dead of their original disease (32 percent) and only 40 percent remained clinically improved. The temporary improvement is attributed by the authors to a placebo effect and to the more frequent attention given the patients by physicians and nurses during a long treatment period. This study also showed that chelation therapy does not significantly alter the natural history of coronary disease, nor does it offer any protection against repeated infarctions and death. Of the first group of patients, 50 Communications to the Editor

percent were dead within four years, and 25 percent of 28 other patients had died within 18 months following courses of EDTA. This is the best evidence to date that chelation therapy with the disodium salt of EDTA is not a useful method of treatment of coronary heart disease. Alex Silverglade, M.D. (Retired Medical Director 3M/ Riker Laboratories, Inc.), Beverly Hills, CA

REFERENCE 1 Kitchell ]R, Palmon F ]r, Aytan N, Meltzer LE. The treatment of

coronary artery disease with disodium EDTA. A reappraisal. Am J Cardiol 1963; 11:501-06

Variable Tracheal Stenosis Related to Body Position To the Editor:

The excellent article by Calhoun and Davis, which appeared in Chest in July, 1984, (86:87-9) made a statement the significance of which may have been overlooked. The statement read, A vertical midline tracheostomy using sharp dissection techniques was performed after 29 days of positive pressure ventilation. There was no resection of tracheal rings and no flap was developed. A soft tracheostomy tube was placed, equipped with a low-pressure, high-volume cuff. There was no clinical evidence of stomal infection at any time during the maintenance of the tracheostomy although sputum cultures grew four different isolates of enteric bacteria. Because of this, the authors seemed to be (justifiably) somewhat puzzled that a tracheal obstruction developed at the stomal site. As a thoracic surgeon, I would like to propose that the variable obstruction (tracheal malacia) was a result not of the well done tracheostomy, but that it was the result of 29 days of cuff pressure from the prior translaryngeal tube. Study of the reproduction of the tracheal tomograms in the article shows that the site of the cuff of an endotracheal tube could very well have been at the level of the demonstrated variable tracheal stenosis. In other words, the surgeon made his tracheal stoma in an area that was already damaged by 29 days of cuff pressure; an area that was destined to go on to the malacial variable stenosis whether a tracheostomy had been done or not. It appears to me that this was a complication of the prolonged translaryngeal intubation and not a complication due to the tracheostomy. In the medical literature, complications are often blamed on the tracheostomy that follows the translaryngeal intubation that has already caused the injuries which go on to later stenosis, -at the cuff level or in the subglottic or cord level. Calhoun and Davis state, "This lesion developed as a consequence of technically adequate tracheostomy free from infectious complications. The event probably represents an unusual manifestation of a common complication." It would be interesting to have the opinion of the operating surgeon as to the cause of this variable tracheal stenosis. Does he think the "lesion developed as a consequence of technically adequate tracheostomy free from infectious complications," or does he think it was a consequence of 29 days of translaryngeal cuff pressure? It would also be of interest and of some pertinence to know what the cuff pressures and systemic airway pressures had been during the 29 days of translaryngeal intubation. Even so-called "low-pressure" cuffs can develop high pressures. P. Ciaglia, M.D .. F.C.C.P. Utica, Neu: York

To the Editor:

We thank Dr. Ciaglia for his interest in and comments regarding our recent publication. We, too, recognize the complications and morbidity which can result from translaryngeal endotracheal intubation. Establishing causal links in medicine remains difficult, and Dr. Ciaglia correctly points out that translaryngeal tracheal intubation is associated with many of the complications ascribed to tracheostomy. However, we believe that the variable stenosis we described developed as a consequence of tracheostomy rather than from endotracheal tube (ET) cuff pressure for several reasons. First, chest radiographs were obtained nearly daily, in part to assess ET position. The tip of the ET was maintained within several centimeters of the carina, suggesting that any cuff injury would have been largely confined to the intrathoracic trachea. Secondly, the operative report does not state or suggest the presence of any cartilaginous or mucosal injury at the stomal site. Lastly, the site of the stenosis seen by tomography is 4-6 cm superior to the site of the cuff of an ET in usual position. Peak airway pressures during the period of ET residence ranged from 50-65 cm H 20; on a few occasions, peak pressure reached 75 cm H 20. Cuff pressure was adjusted daily. Only sufficient air was added to prevent a peri-cuff air leak. We concur that a "low-pressure" cuff adjusted in this way may develop high pressure, but we believe that the evidence suggests a procedural complication rather than one related to the ET cuff was responsible for the anatomic abnormality. Tracheal access, via an ET or tracheostomy, carries risks which must be considered in the care of seriously ill patients. William]. Calhoun, M.D.; and Gerald S. Davis, M.D., F.C.C.P. Pulmonary Unit, University ofVennont College ofMedicine, Burlington

Multidrug Resistance in M fortuitum To the Editor:

In the article by Martin and Dall on the "Emergence of multidrug resistant Mycobacterium [ortuitum during treatment" (Chest 1984; 85:440-41), the data on susceptibility testing do not provide definite evidence of acquired multidrug resistance and the potential usefulness of erythromycin against M [ortuitum was over-estimated. Although susceptibility testing was said to be by disk diffusion, we suspect the values obtained in March 1982 were by the proportion method in agar since commercial disks of the sizes listed in Table 1 were not available. If these tests were done using paper disks, the drug concentrations were different from those used in May, 1982, and thus, comparison of the significance of changes in the size of zones of inhibition would be almost impossible. The second and third sets of susceptibility results presumably were by disk diffusion. Disk zone diameters which characterize strains susceptible to streptomycin and strains susceptible or resistant to ethionamide have not been published to our knowledge, so even if the disk diffusion tests in May, 1982 resulted in no zone of inhibition around the disk, one cannot know if the MICs had changed from the first test done by a different method. The 30 ~g cefoxitin disk which was used has not been reliable in our studies for susceptibility testing by disk diffusion as the drug content is inadequate to detect susceptibility in all isolates (ie, some isolates which we consider susceptible with produce no zones of inhibition). The study by MICs of 32 ~g/ml Cynamon and Patapow' includes the only 13 isolates for which zone sizes have been published for cefoxitin. As with streptomycin and ethionamide, zone diameters which correlate to susceptible or resistant MICs have not been determined for cefoxitin, so even a CHEST / 87 / 2 / FEBRUARY, 1985

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