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Level IV Neck Dissection in Laryngeal Carcinoma
Vol. 203, No. 1, July 2006
milieu and preexisting mild proinflammatory state and sarcopenia.10,11 We are grateful to Dr Wolfe for emphasizing the importance of this topic in the older population. The premises are good. The time for a randomized clinical trial to test this hypothesis has arrived. REFERENCES 1. Wolfe RR. Optimal nutrition, exercise, and hormonal therapy promote muscle anabolism in the elderly. J Am Coll Surg 2006; 202:176–180. 2. Fried L, Walston J. Frailty and failure to thrive. In Principles of Geriatric Gerontology, 5th ed. Hazzard WR, Blass JP, Ettinger WH Jr, et al, eds. New York: McGraw Hill, 2003:1487⫺1502. 3. Cappola AR, Xue QL, Ferrucci L, et al. Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 2003; 88:2019–2025. 4. Maggio M, Ceda GP, De Cicco G, et al. Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting. J Endocrinol Invest 2005;28:711–719. 5. Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006; 27:135–137. 6. Ferrando AA, Sheffield-Moore M, Yeckel CW, et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 2002;282:E601–E607. 7. Malkin CJ, Pugh PJ, Jones RD, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89:3313–3318. 8. Maggio M, Basaria S, Ble A, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor (sIL-6r) in older men. J Clin Endocrinol Metab 2006;91: 345–347. 9. Guler N, Batyraliev T, Dulger H, et al. The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting. Int J Cardiol July 22, 2005. [Epub ahead of print] 10. Ferrucci L, Corsi A, Lauretani F, et al. The origins of age-related proinflammatory state. Blood 2005;105:2294–2299. 11. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997;278:419–424.
Level IV Neck Dissection in Laryngeal Carcinoma Sheng-Po Hao, MD, FACS, FICS Taipei, Taiwan I read with great interest the article, “Do pathologic and molecular analyses of neck dissection specimens justify
Letters
135
the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck?” by Dr Elsheikh and colleagues.1 The authors present an interesting and important observation on critical issues concerning level IV node metastasis of laryngeal carcinoma. I am particularly concerned about the conclusion made in this article, stating, “Using immunohistochemistry and in addition, developing the genetic diagnosis of occult metastases, we shall probably discover that selective neck dissection (IIA, III) is justified for patients with supraglottic and glottic squamous carcinoma with a clinically N0 neck, and transglottic and primary subglottic tumors will also require level IV dissection.” The authors also stated, “So, level IV dissection may not be necessary for supraglottic and glottic tumors in N0 necks. But transglottic and primary subglottic tumors may well require level IV dissection.” It is well known that transglottic carcinoma represents a group of glottic cancers that include paraglottic space invasion.2,3 Clinically, transglottic carcinoma usually crosses Morgagni’s ventricle in a vertical plain and involves glottic and supraglottic sites. It is sometimes possible, but not always, for a transglottic cancer to involve subglottis. Khafif and coworkers4 reported on 71 patients, including 42 with supraglottic primary and 29 with transglottic primary cancers, who underwent neck dissections, which included levels II and IV in all patients. They found that of 43 patients who underwent elective lateral neck dissection, the only 1 (2.3%) with level IV metastases also showed metastases at level II. Nine (32%) of the other 28 patients with clinical adenopathy had level IV metastases. They concluded that dissection of level IV as part of a therapeutic neck dissection for supraglottic and transglottic squamous cell carcinoma is recommended for patients with clinically enlarged lymph nodes, but its necessity in the absence of detectable adenopathy is challenged. I agree with the authors that “Lymphatic collectors of the supraglottic and glottic larynx drain primarily into level II and secondarily into level III cervical lymph nodes; the lymphatic vessels of the subglottic drain primarily into level IV lymph nodes.1 But I postulate that the patients who have transglottic cancer with metastatic level IV nodes either have other metastatic nodes at levels II and III or have subglottic invasion. I wonder if a transglottic cancer without subglottic invasion or clinically enlarged nodes will also require level IV dissection.
136
Letters
REFERENCES 1. Elsheikh MN, Ferlito A, Rinaldo A, et al. Do pathologic and molecular analyses of neck dissection specimens justify the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck? J Am Coll Surg 2006;202:320–323. 2. Hao SP, Myers EN, Johnson JT. T3 glottic carcinoma revisited, transglottic vs pure glottic carcinoma. Arch Otolaryngol Head Neck Surg 1995;121:166–170. 3. Kirchner JA. Two hundred laryngeal cancers: patterns of growth and spread as seen in serial section. Laryngoscope 1997;87:474– 482. 4. Khafif A, Fliss DM, Gil Z, Medina JE. Routine inclusion of level IV in neck dissection for squamous cell carcinoma of the larynx: is it justified? Head Neck 2004;26:309–312.
Reply Mohamed N Elsheikh, MD Tanta, Egypt Alfio Ferlito, MD, FACS, Alessandra Rinaldo, MD Udine, Italy Ashok R Shaha, MD, FACS New York, NY Avi Khafif, MD Tel-Aviv, Israel Hakan H Coskun, MD Bursa, Turkey Luiz P Kowalski, MD São Paulo, Brazil Jesus E Medina, MD, FACS Oklahoma City, OK We have read the interesting letter from Dr Hao concerning our article “Do pathologic and molecular analyses of neck dissection specimens justify the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck?”1 In this article, we concluded that the data from several pathologic and molecular analyses of neck dissection specimens from patients with laryngeal squamous carcinoma and a clinically N0 neck have demonstrated a low incidence of positive nodes at level IV. Thi is not enough to justify a standardized selective neck dissection (IIA,
J Am Coll Surg
III). Using immunohistochemistry and the genetic diagnosis of occult metastases may determine that selective neck dissection (IIA, III) is justified for patients with supraglottic and glottic squamous carcinoma with a clinically N0 neck, and transglottic and primary subglottic tumors could well require level IV dissection. In his letter, Dr Hao postulated that the patients who have transglottic cancer with metastatic level IV nodes either have other metastatic nodes at level IIs and III or have subglottic invasion. So he wondered if a transglottic cancer without subglottic invasion or clinically enlarged nodes would also require level IV dissection. Transglottic cancer means that the tumor has invaded the paraglottic space. The paraglottic space is in continuity from the supraglottis down to the subglottis, and there is no boundary within this space. So, a transglottic cancer can easily metastasize as a subglottic cancer. Based on the strength of the current pathologic and molecular studies on the pattern of nodal metastasis in patients with squamous carcinoma of the larynx, we cannot accept or decline Dr Hao’s optimistic suggestion. Many surgeons still stress that group IV should be included not only with transglottic, but even with supraglottic carcinoma. Elsheikh and colleagues2 prospectively examined 31 previously untreated consecutive patients with squamous carcinoma of the larynx (9 of them were transglottic). The incidence of metastases to level IV after elective selective neck dissection (II–IV) was evaluated by nested reverse transcriptase-polymerase chain reaction for cytokeratin 19 and cytokeratin 20, and by pathologic examination. Based on the two molecular markers, the incidence of occult positive lymph nodes was 29% (9 of 31) and level IV was involved in 1 of the 9 patients. This metastasis was detected by both pathologic and molecular analyses. The incidence of metastases to level IV in transglottic carcinoma was consequently 11% (1 of 9). The patient with a positive level IV had a T3N0 transglottic cancer. In this patient, an isolated metastasis to this level occurred without any involvement of the other lymph nodes in the selective neck dissection specimen. This may mean that skip metastases to level IV are a potential problem. To date, many pathologic and few molecular analysis studies have identified a low incidence of involvement to level IV, but this is not enough to justify a standardized selective neck dissection (IIA, III). In addition, concern
milieu and preexisting mild proinflammatory state and sarcopenia.10,11 We are grateful to Dr Wolfe for emphasizing the importance of this topic in the older population. The premises are good. The time for a randomized clinical trial to test this hypothesis has arrived. REFERENCES 1. Wolfe RR. Optimal nutrition, exercise, and hormonal therapy promote muscle anabolism in the elderly. J Am Coll Surg 2006; 202:176–180. 2. Fried L, Walston J. Frailty and failure to thrive. In Principles of Geriatric Gerontology, 5th ed. Hazzard WR, Blass JP, Ettinger WH Jr, et al, eds. New York: McGraw Hill, 2003:1487⫺1502. 3. Cappola AR, Xue QL, Ferrucci L, et al. Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 2003; 88:2019–2025. 4. Maggio M, Ceda GP, De Cicco G, et al. Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting. J Endocrinol Invest 2005;28:711–719. 5. Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006; 27:135–137. 6. Ferrando AA, Sheffield-Moore M, Yeckel CW, et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 2002;282:E601–E607. 7. Malkin CJ, Pugh PJ, Jones RD, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89:3313–3318. 8. Maggio M, Basaria S, Ble A, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor (sIL-6r) in older men. J Clin Endocrinol Metab 2006;91: 345–347. 9. Guler N, Batyraliev T, Dulger H, et al. The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting. Int J Cardiol July 22, 2005. [Epub ahead of print] 10. Ferrucci L, Corsi A, Lauretani F, et al. The origins of age-related proinflammatory state. Blood 2005;105:2294–2299. 11. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997;278:419–424.
Level IV Neck Dissection in Laryngeal Carcinoma Sheng-Po Hao, MD, FACS, FICS Taipei, Taiwan I read with great interest the article, “Do pathologic and molecular analyses of neck dissection specimens justify
Letters
135
the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck?” by Dr Elsheikh and colleagues.1 The authors present an interesting and important observation on critical issues concerning level IV node metastasis of laryngeal carcinoma. I am particularly concerned about the conclusion made in this article, stating, “Using immunohistochemistry and in addition, developing the genetic diagnosis of occult metastases, we shall probably discover that selective neck dissection (IIA, III) is justified for patients with supraglottic and glottic squamous carcinoma with a clinically N0 neck, and transglottic and primary subglottic tumors will also require level IV dissection.” The authors also stated, “So, level IV dissection may not be necessary for supraglottic and glottic tumors in N0 necks. But transglottic and primary subglottic tumors may well require level IV dissection.” It is well known that transglottic carcinoma represents a group of glottic cancers that include paraglottic space invasion.2,3 Clinically, transglottic carcinoma usually crosses Morgagni’s ventricle in a vertical plain and involves glottic and supraglottic sites. It is sometimes possible, but not always, for a transglottic cancer to involve subglottis. Khafif and coworkers4 reported on 71 patients, including 42 with supraglottic primary and 29 with transglottic primary cancers, who underwent neck dissections, which included levels II and IV in all patients. They found that of 43 patients who underwent elective lateral neck dissection, the only 1 (2.3%) with level IV metastases also showed metastases at level II. Nine (32%) of the other 28 patients with clinical adenopathy had level IV metastases. They concluded that dissection of level IV as part of a therapeutic neck dissection for supraglottic and transglottic squamous cell carcinoma is recommended for patients with clinically enlarged lymph nodes, but its necessity in the absence of detectable adenopathy is challenged. I agree with the authors that “Lymphatic collectors of the supraglottic and glottic larynx drain primarily into level II and secondarily into level III cervical lymph nodes; the lymphatic vessels of the subglottic drain primarily into level IV lymph nodes.1 But I postulate that the patients who have transglottic cancer with metastatic level IV nodes either have other metastatic nodes at levels II and III or have subglottic invasion. I wonder if a transglottic cancer without subglottic invasion or clinically enlarged nodes will also require level IV dissection.
136
Letters
REFERENCES 1. Elsheikh MN, Ferlito A, Rinaldo A, et al. Do pathologic and molecular analyses of neck dissection specimens justify the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck? J Am Coll Surg 2006;202:320–323. 2. Hao SP, Myers EN, Johnson JT. T3 glottic carcinoma revisited, transglottic vs pure glottic carcinoma. Arch Otolaryngol Head Neck Surg 1995;121:166–170. 3. Kirchner JA. Two hundred laryngeal cancers: patterns of growth and spread as seen in serial section. Laryngoscope 1997;87:474– 482. 4. Khafif A, Fliss DM, Gil Z, Medina JE. Routine inclusion of level IV in neck dissection for squamous cell carcinoma of the larynx: is it justified? Head Neck 2004;26:309–312.
Reply Mohamed N Elsheikh, MD Tanta, Egypt Alfio Ferlito, MD, FACS, Alessandra Rinaldo, MD Udine, Italy Ashok R Shaha, MD, FACS New York, NY Avi Khafif, MD Tel-Aviv, Israel Hakan H Coskun, MD Bursa, Turkey Luiz P Kowalski, MD São Paulo, Brazil Jesus E Medina, MD, FACS Oklahoma City, OK We have read the interesting letter from Dr Hao concerning our article “Do pathologic and molecular analyses of neck dissection specimens justify the preservation of level IV for laryngeal squamous carcinoma with clinically negative neck?”1 In this article, we concluded that the data from several pathologic and molecular analyses of neck dissection specimens from patients with laryngeal squamous carcinoma and a clinically N0 neck have demonstrated a low incidence of positive nodes at level IV. Thi is not enough to justify a standardized selective neck dissection (IIA,
J Am Coll Surg
III). Using immunohistochemistry and the genetic diagnosis of occult metastases may determine that selective neck dissection (IIA, III) is justified for patients with supraglottic and glottic squamous carcinoma with a clinically N0 neck, and transglottic and primary subglottic tumors could well require level IV dissection. In his letter, Dr Hao postulated that the patients who have transglottic cancer with metastatic level IV nodes either have other metastatic nodes at level IIs and III or have subglottic invasion. So he wondered if a transglottic cancer without subglottic invasion or clinically enlarged nodes would also require level IV dissection. Transglottic cancer means that the tumor has invaded the paraglottic space. The paraglottic space is in continuity from the supraglottis down to the subglottis, and there is no boundary within this space. So, a transglottic cancer can easily metastasize as a subglottic cancer. Based on the strength of the current pathologic and molecular studies on the pattern of nodal metastasis in patients with squamous carcinoma of the larynx, we cannot accept or decline Dr Hao’s optimistic suggestion. Many surgeons still stress that group IV should be included not only with transglottic, but even with supraglottic carcinoma. Elsheikh and colleagues2 prospectively examined 31 previously untreated consecutive patients with squamous carcinoma of the larynx (9 of them were transglottic). The incidence of metastases to level IV after elective selective neck dissection (II–IV) was evaluated by nested reverse transcriptase-polymerase chain reaction for cytokeratin 19 and cytokeratin 20, and by pathologic examination. Based on the two molecular markers, the incidence of occult positive lymph nodes was 29% (9 of 31) and level IV was involved in 1 of the 9 patients. This metastasis was detected by both pathologic and molecular analyses. The incidence of metastases to level IV in transglottic carcinoma was consequently 11% (1 of 9). The patient with a positive level IV had a T3N0 transglottic cancer. In this patient, an isolated metastasis to this level occurred without any involvement of the other lymph nodes in the selective neck dissection specimen. This may mean that skip metastases to level IV are a potential problem. To date, many pathologic and few molecular analysis studies have identified a low incidence of involvement to level IV, but this is not enough to justify a standardized selective neck dissection (IIA, III). In addition, concern