Fine-Needle Aspiration and Tumor Seeding

esophageal sphincter (LES). During SAS4 (and upper airway resistance syndrome5), there is increased respiratory effort by the diaphragm. This extra effort is transmitted to the LES by the PEL. Only when the force transmitted to LES exceeds that threshold will the LES open and allow gastric fluids to enter the esophagus. Penzel et al2 reported that reflux does not occur with every apnea. Although that article did not consider upper airway resistance syndrome, in 68 of 69 observed reflux events, reflux was associated with “arousals.” It is suggested that “sleep-related breathing disorders” should be considered in all cases of GERD because children6 as well as adults are subject to sleep-related breathing disorders. Joseph Herr Alamo, CA Correspondence to: Joseph Herr, 2109 Granite Dr, Alamo, CA 94507-1602

References 1 Teramoto S, Ouchi Y. A possible pathologic link between chronic cough and sleep apnea syndrome through gastroesophageal reflux disease in older people [letter]. Chest 2000; 117;1215–1216 2 Penzel T, Becker H, Brandenburg U, et al. Arousal in patients with gastro-oesophageal reflux and sleep apnoea. Eur Respir J 1999; 14:1266 –1270 3 Stiennon O. The longitudinal muscle in esophageal disease. Madison, WI: WRS Press, 1985 4 Guilleminault C. Obstructive sleep apnea: the clinical syndrome and historical perspective. Med Clin North Am 1985; 69:1187–1203 5 Guilleminault C, Stoohs R, Clerk A, et al. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Chest 1993; 104:781–787 6 Guilleminault C, Pelayo R. Sleep-disordered breathing in children. Ann Med 1998; 30:350 –356

laryngitis, and chronic coughing, the pathologic link among chronic cough, SAS, and GERD is not simply determined in children. Shinji Teramoto, MD, FCCP Takeo Ishii, MD Takeshi Matsuse, MD International University of Health and Welfare Tokyo, Japan Correspondence to: Shinji Teramoto, MD, FCCP, International University of Health and Welfare, Department of Pulmonary Medicine, Sanno Hospital, 8-10-16 Akasaka Minato-ku, Tokyo, Japan 107-0052; e-mail: [email protected]

References 1 Teramoto S, Ouchi Y. A possible pathologic link between chronic cough and sleep apnea syndrome through gastroesophageal reflux disease in older people [letter]. Chest 2000; 117:1215–1216 2 Samelson CF. Gastroesophageal reflux and obstructive sleep apnea. Sleep 1989; 12:475– 476 3 Diaz S, Esteban E, Piro JM, et al. Utility of CPAP in gastroesophageal reflux [letter]. Chest 1990; 97:1275 4 Kerr P, Shoenut JP, Miller T, et al. Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome. Chest 1992; 101:1539 –1544 5 Teramoto S, Ohga E, Matsui H, et al. Obstructive sleep apnea syndrome may be a significant cause of gastroesophageal reflux disease in the elderly. J Am Geriatr Soc 1999; 47:1273– 1274 6 Teramoto S, Sudo E, Ohga E, et al. Impaired swallowing reflex in patients with obstructive sleep apnea syndrome. Chest 1999; 116:17–21

Fine-Needle Aspiration and Tumor Seeding

To the Editor: To the Editor: We appreciated Herr’s comments on our article.1 As suggested by Herr, the possible pathologic link between chronic cough and sleep apneas through gastroesophageal reflux disease (GERD) may be extended to children as well as adults. Although the pathologic link between sleep apneas and GERD have reported by several investigators,2–5 the pathologic link between chronic cough and sleep apneas has not been established. Thus, we have to consider carefully the significant association of chronic cough with sleep apneas. In particular, the fundamental mechanism of sleep-disordered breathing in children may not be the same as that of sleep apneas in adults and the elderly. We do not have enough evidence concerning the chronic cough associated with sleep apneas or GERD in younger subjects and children. However, it is interesting to know the swallowing function in child patients and older patients with sleep apneas or GERD. Because the swallowing function is impaired in patients with sleep apnea syndrome (SAS),6 and because the swallowing function is associated with cough reflex thorough substance P, the abnormality in swallowing function in SAS may be associated with chronic cough in children and adults. Although many patients with adults SAS complain of sleep-related heartburn and regurgitation of gastric contents into the pharynx,2–5 the complaint was rarely heard in children with apneas. Therefore, the similarities and differences in swallowing function, cough reflex, and gastroesophageal reflux between children and adult patients with SAS may lead to further knowledge regarding the coupling mechanism between respiration and deglutition. However, as GERD manifests a spectrum of conditions, including asthma, posterior

We read with great interest the article by Sawabata and associates1 in CHEST (October 2000). The authors present data of a study concerning the potential of malignant cell spread with fine-needle aspiration. Although physicians in some institutions perform fine-needle aspiration routinely and safely in order to obtain histologic diagnosis of thoracic masses with a high rate of accuracy,2 a number of centers do not utilize this method because of possible complications, such as seeding and pneumothorax, especially in patients with COPD. We would like to express a few of our comments on that study. Firstly, concerning the utilized model of the study, the lung was deflated during and after fine-needle aspiration. Therefore, there is a lack of a counter-balancing effect against the chest wall and a lack of sealing function against the shedding possibility of tumor cells. Since the opposed tissue pressure created by inflated airways and alveoli was decreased in a deflated lung, theoretically tumor cells might anticipate less intercellular pressure of extracellular matrix; therefore, the possible chance for tumor cells to exfoliate outside the lung could be suggested to be higher than that of living lung. That hypothesis could have been tested by comparison of the presence of tumor cells in the pleural irrigation fluid from the fine-needle aspirated deflated and artificially reinflated specimens. We think that that would be the necessary negative control of the study group. In the study, it was reported that the number of spilled tumor cells was found to be higher, but increased tumor cell shedding does not necessarily result in successful implantation of the CHEST / 120 / 3 / SEPTEMBER, 2001

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tumor cell population because of the resistance of immune system of the host against tumor cells as proposed by the “immune surveillance” theory.3 In order to test this possibility, aspiration tracts could be pathologically examined. Implantation of tumor cells has been known to be extremely rare, such as 1 in 4,000 transthoracic needle biopsy procedures,4 and has been the subject of a few case reports in medical journals. This study also inspired us to search for evidence of poorer survival in inoperable stage-matched patients who underwent fine-needle aspiration for diagnosis. We were unable to find any study on this respect. For this reason, we think it is unlikely that needle aspiration has a perilous tumor seeding effect in terms of tumor implantation risk in those patients. We are also grateful for that hypothesis-creating innovative study, which could be a basis of further studies. Mehmet Ali Bedirhan, MD Akif Turna, MD Istanbul, Turkey Correspondence to: Akif Turna, MD, Cami Sok, Muminderesi Yolu, Emintas Camlik Sit, No:32/22, Sahrayicedid, Kadikoy 81080 Istanbul, Turkey; e-mail: [email protected]

References 1 Sawabata N, Mitsunori O, Maeda H. Fine-needle aspiration cytologic technique for lung cancer has a high potential of malignant cell spread through the tract. Chest 2000; 118:936 –939 2 Kosar F, Altin S, Kiyik M, et al. Transthoracic fine needle aspiration in evaluation of chest lesions suspicious for malignancy: advances in imaging guidance [abstract]. Eur Respir J 1996; 9:57S 3 Bast RC, Mills GB, Gibson S, et al. Tumor immunology. In: Holland JF, Bast RC, Morton DL, et al, eds. Cancer medicine. Baltimore, MD: Williams & Wilkins, 1997; 207–242 4 Nordenstrom B, et al. Dissemination of cancer cells by needle biopsy of lung [letter]. Thorac Cardiovasc Surg 1973; 65:671 To the Editor: I appreciate the response to our article1 concerning the potential of malignant cell spread following fine-needle aspiration cytology (FNAC) from Dr. Bedirhan and Dr. Turna. They pointed out the dissociation between an in vivo and ex vivo lung. As they said, the inflated lung over the tumor can protect against the spread of malignant cells through the tract following FNAC. However, most of the tumors that underwent FNAC were peripherally located and associated with pleural indentation. Thus, the lung over the tumor does not seem to be completely inflated. And so I believe the possibility of spreading tumor cells is similar between an in vivo and ex vivo lung. I also believe in the “immune surveillance theory.” Effusionassociated lymphocytes are revealed to have depressed cellular function in the malignant effusion with lung cancer.2 And so it is speculated that the spread of malignant cells has a low potential of implantation. Surgical patients with lung cancer have a good performance status and may have a normal immune function. We have performed a retrospective study,3 which revealed the technique did not affect relapse and survival. By contrast, patients with advanced lung cancer may have a depressed immune system. Therefore, it is important to search for evidence of pleural carcinomatosis and poorer survival in inoperable patients with advanced lung cancer. To summarize our opinion, FNAC has the potential to seed malignant cells that rarely implant among operable patients, but 1038

the possibility of implantation is controversial among inoperable patients with advanced lung cancer. Noriyoshi Sawabata, MD, FCCP Toneyama National Hospital Osaka, Japan Correspondence to: Noriyoshi Sawabata, MD, FCCP, Division of Surgery, Toneyama National Hospital, 5-1-1 Toneyaman Toyonaka, Osaka, 560-8552 Japan; e-mail: [email protected]

References 1 Sawabata N, Ohta M, Maeda H. Fine-needle aspiration cytologic technique for lung cancer has a high potential of malignant cell spread through the tract. Chest 2000; 118:936 – 939 2 Chen YM, Tang WK, Ting CC, et al. Cross regulation by IL-10 and IL2-/IL12 of the helper T cell and the cytolotic activity of lymphocytes from malignant effusion of lung cancer patients. Chest 1997; 112:960 –966 3 Sawabata N, Maeda H, Ohta M. Operable non-small cell lung cancer diagnosed by transpleural techniques: do they affect relapse and prognosis? Chest 2001 (in press)

Dextromethorphan in Pregnancy To the Editor: We noted with interest the article in CHEST by Einarson et al (February 2001)1 focusing on the teratogenicity of dextromethorphan. The merit of the authors is to point out a low or absent teratogenic potential of dextromethorphan. However, apart from the investigation of its teratogenic effects, the substance might have other serious side effects that have to be considered. The nitrogen-bound-methyl-dextro-aspartate (NMDA) receptor plays an important role in the developing mammalian brain with respect to the establishment of synaptic connections and learning processes. Antagonists of the NMDA receptor potentially disrupt these processes; this has been clearly shown2 in animal models but not yet in man. Further observations3 refer to the fact that NMDA-receptor blocking agents enhance apoptotic neurodegeneration in the developing brain. This was shown4 for different NMDA-receptor antagonists including alcohol. From the standpoint of pediatric neurology, we are in fact very interested in the field of NMDA blockade with regard to the treatment of severe epilepsy or to neuroprotection. The underlying pathophysiology comprises overstimulation of the NMDA receptor by excitatory amino acids like glycine or glutamate. In certain epileptic disorders, dextromethorphan medication is established as an anticonvulsant.5 In nonketotic hyperglycinemia, for instance, an inborn metabolic dysfunction, in molybdenum cofactor deficiency, and in early infantile epileptic encephalopathy (Ohtahara syndrome), it can be helpful.6 – 8 Furthermore, dextromethorphan was used for neuroprotection in children undergoing cardiac surgery9 or suffering from bacterial meningitis.10 The above findings2– 4 led, however, to the withdrawal of further clinical studies. Theoretically, all mechanisms involved in antagonizing the NMDA receptor might threaten the developing brain of fetuses as well, similar to the neuronal damage of fetuses exposed to alcohol. To our knowledge, no neurodevelopmental data exist on offspring of mothers who received dextromethorphan during their pregnancies. We therefore feel that dextromethorphan should be administered with the utmost Communications to the Editor