Giancarlo Roviaro, MD, FCCP; Federico Varoli, MD; Contardo Vergani, MD; Ombretta Nucca, MD; Marco Maciocco, MD; and Fabrizio Grignani, MD

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1 Giancarlo Roviaro, MD, FCCP; Federico Varoli, MD; Contardo Vergani, MD; Ombretta Nucca, MD; Marco Maciocco, MD; and Fabrizio Grignani, MD San Giuseppe (18 39 ) Kaplan-Meier 3 5 y 77.7% 63.64% T1N0 3 5 y ( 83.50% 70.21%) T2N0 ( 71.13% 56.12%) y ( 82.37% 73.32%) 70 ( 57.49% 37.09%) (P < 0.01) (bronchogenic carcinoma); (pulmonary lobectomy); (survival); (video-assisted thoracic surgery); (video-assisted thoracic surgery lobectomy) [4~8] [1~3] 10 y ( ) CHEST

2 [9~12] 3 5 y [13] 3 ~ 4 cm 57 ( ) N1 N ( CT ) ( 1) (87 T1N0 78 T2N0) 28 7 (6 (22 N1,6 N2) 1 ) (1991 (1) T1N ) (1) T2N0 < 3 cm (2) (3) (4) [2,14~17] (1) From the Department of Surgical Sciences (Drs. Roviaro, Vergani, and Maciocco), University of Milan, and Department of Surgery, Ospedale Maggiore Policlinico IRCCS, Milan; and Department of Surgery (Drs. Varoli, Nucca, and Grignani), Ospedale San Giuseppe Fbf, A. Fa. R Milan, Italy. Correspondence to: Giancarlo Roviaro, MD, FCCP, University of Milan, Ospedale Maggiore Policlinico IRCCS, Milan, Pad. Zonda, Via Francesco Sforza, 35, Milan, Italy; e- mail: gian. roviaro@unimi. it ( ) (1) (1) 572

3 % (95%CI 8.9) 70.2% (95% CI 12.4); T2N0 3 5 y 71.1% (95% CI 11.6) % (95% CI 14.2)] ( 1); A B ( 2) [3 y 68.9% (95% CI 13.5) 5 y % (95% CI 14.5)] [3 y t / mo 83.9% (95% CI 8.3) 5 y 63.3% (95% CI 1 13)] ( 3) y 3 5 y Kaplan-Meier 70 (P < 0.01) 15 ( y 82.3% (95% 5 4 CI 8.7) 72.3% (95% CI 11.3); y 57.5% (95% CI 16.4) 37.1% (95% CI 18) ( 4) 5 y) 60 d 2 (1.03%) d 6 1 y [3~5,7,8,10,12,14] 1 (Office of Vital Statistics) 15 2 ( ( 5 y) Kaplan-Meier Kaplan-Meier ) (11 ~ 78 ) TNM 4 T2N T2N0 4 ( T1N0 ) 2 3 mo 5 ( ) 5 T1N0 0.5 t / mo Kaplan-Meier 3 5 y 77.7% 2 T1N0 T2N0 [95% (confidence index CI) 7.3] Kaplan-Meier 63.6% (95% CI 9.4) T1N0 3 5 y T1N0 3 5 y A B T2N0 [T1N0 3 5 y CHEST

4 t / mo 14 N1 N2 22 (11.4%) N1 6 (3.1%) N2 3 Kaplan-Meier [5,20] 2 ( 5 y [22,23] ) [2,3] 327 ( ) [5] [18] 0.9 [19] [5,18~20] 0.6 > 70 < 70 < 70 [4~9] 1997 Mack [21] 0.3 ( ) t / mo [1] Kaplan-Meier >

5 ( ) (non-small cell lung cancer NSCLC) 3 y 57.8% 5 y 46.9% NSCLC y 36.89% [24,25] [26~30] 5 y A (T1N0) [13,31,37] 54% ~ 83% B (T2N0) 37% ~ 65% -α IL-1β IL-6 IL-10 [5,8~12,19,31] ( 3) [11,18] 3 y 77.75% 5 y 63.64% 70 3 y 57.49% 5 y 37.09% 70 3 y 82.37% 5 y [13,32~36] IgG C (interleukin IL)-6 ( 72.32% ) (P < 0.01) ( 3) 1 Roviaro GC, et al. Surg Laparosc Endosc 1992; 2: Roviaro GC, et al. Ann Thorac Surg 1993; 56: Kirby TJ, et al. Ann Thorac Surg 1993; 56: Loscertales J, et al. Eur J Cardiothorac Surg 1997; 12: McKenna RJ Jr, et al. Semin Thorac Cardiovasc Surg 1998; 10: Shennib HA, et al. Ann Surg 1993; 218: Walker WS. Semin Thorac Cardiovasc Surg 1998; 10: Yim APC, et al. Semin Thorac Cardiovasc Surg 1998; 10: Kaseda S, et al. Ann Thorac Surg 2000; 70: Naruke T. In: Yim APC, et al, eds. Minimal access cardiothoracic surgery.philadelphia, PA: WB Saunders, 2000; Walker SW, et al. Eur J Cardiothorac Surg 2003; 23: Kaseda S, et al. Semin Thorac Cardiovasc Surg 1998; 10:300-3 (%) 2 y 3 y 4 y 5 y Yim [8](1) McKenna [5](1) Kaseda [9](2) Naruke [10](2) Sugi [31](2) Walker [11](2) Roviaro ( ) (2) (1) (2) CHEST

6 Walker WS, et al. In:Yim APC, et al. eds. Minimal access cardiothoracic surgery. Philadelphia, PA: WB Saunders, 2000; Roviaro GC, et al. Semin Thorac Cardiovasc Surg 1998;10: Roviaro GC, et al. Int Surg 1993; 78: Roviaro GC, et al. In: Yim APC, et al, eds.minimal access cardiothoracic surgery. Philadelphia, PA: WB Saunders, 2000; Roviaro GC, et al. Chest Surg Clin N Am 1999; 9: Lewis RJ, et al. Semin Thorac Cardiovasc Surg 1998; 10: Yim APC. Ann Thorac Surg 2002;74: McKenna RJ Jr, et al. Ann Thorac Surg 1998; 66: Mack MJ, et al. Ann Thorac Surg 1997; 64: Roviaro GC, et al. Ann Thorac Surg 1995;59: Roviaro GC, et al. Int Surg 1996; 81: American Joint Committee on Cancer. In: Greene FL, et al, eds. AJCC cancer staging manual. 6th ed. New York, NY: Springer, 2002; National Cancer Data Base NCDB, Commission on Cancer, AcoS/ ACS. Survival reports, v January 4, Five year survival rates for lung, bronchus-non small cell carcinoma cancer cases diagnosed in 1994 and 1995.All states/data reported from 1663 hospitals. Available at: Accessed June 30, Martini N. Semin Surg Oncol 1990; 6: Williams DE, et al. J Thorac Cardiovasc Surg; 1981; 82: Shields TW, et al. J Thorac Cardiovasc Surg 1978; 76: Mountain CF. Chest 1990; 97: Naruke T, et al. J Thorac Cardiovasc Surg 1988; 96: Sugi K, et al. Jpn J Thorac Cardiovasc Surg 2000;48: Leaver HA, et al. Biologicals 1996; 24: Leaver HA, et al. Eur J Clin Invest 2000; 30: Leaver HA, et al. Eur J Clin Invest 1996; 26:A37,A Carey PD, et al. Br J Surg 1994; 81: Salo M. Acta Anaesth Scand 1996; 36: Yim APC, et al. Ann Thorac Surg 2000; 70: CHEST, 2004;126: CHEST No.10 B. Buffering of hypercapnic acidosis with bicarbonate worsens acute lung injury. Lung protective mechanical ventilation strategies often result in "so-called" permissive hypercapnia. Because physicians associate academia with hypoperfusion and end-orgean failure and because there is concern for adverse hemodynamic effects of acidosis, some authorities recommend the use of bicarbonate therapy to keep blood ph above However, there is little to no evidence that this is beneficial. To the contrary, there is strong experimental evidence that buffering hypercapnic acidosis worsen acute lung injury in ex vivo perfused mechanically ventilated lungs and that hypercapnia per se may exert clinically important organ protection. One proposed mechanism by which hypercapnic acidosis may protect the lungs from injury is inhibition of endogenous xanthine oxidase enzyme activity and the consequent reduction in free radical generation. This mechanism has been examined in detail in lung models of ischemia/reperfusion injury. Alternative mechanisms involve ph-dependent alterations in amiloride sensitive Na-H exchange channels. These microvascular ion channels are important in regulating pulmonary fluid flux. Consistent with this hypothesis is the observation that the administration of bicarbonate raises the pulmonary capillary filtration coefficient and promotes edema formation in isolated perfused lungs. Not only is there evidence that hypercapnic acidosis may be organ protective, there is also evidence that hypocapnic alkalosis has adverse effects on neurologic and cardiovascular outcomes. Hypocapnia accentuates ischemic injury to the brain and myocardium and worsens systemic oxygenation. There is strong evidence that systemic ph regulates the rate of endogenous acid production and that buffering with bicarbonate interferes with this homeostatic mechanisms. For example, the administration of bicarbonate increases the rate of lactate production and raises blood lactate concentration. Option A is therefore incorrect. The same holds true for ketone generation in diabetic ketoacidosis; bicarbonate increases ketone formation as opposed to reducing it as stated in option C. while there are no data to refute the common practice of alkali therapy in severe cases of "permissive hypercapnia," there are equally no data to suggest clinical benefit. Therefore, answer D is incorrect. Finally, the homeostatic feedback mechanism between ph and acid production has implications for metabolic rate; academia lowers oxygen demand, alkalemia increases it. Option E is therefore incorrect. 576