HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Atsushi Watanabe Tetsuya Higami Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, A. Articles by Mawatari, T. Search for Related Content PubMed Articles by Watanabe, A. Articles by Mawatari, T. Related Collections Lung - cancer Lung - other

J Thorac Cardiovasc Surg 2008;136:1357-1363
© 2008 The American Association for Thoracic Surgery

General Thoracic Surgery

Is lung cancer resection indicated in patients with idiopathic pulmonary fibrosis?

Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

Received for publication November 3, 2007; revisions received May 16, 2008; accepted for publication July 5, 2008.

^_* Address for reprints: Atsushi Watanabe, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. (Email: atsushiw{at}sapmed.ac.jp).

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 
Objective: The purpose of this study was to determine the implication of idiopathic pulmonary fibrosis on the surgical treatment for primary lung cancer.

Methods: Between January 1994 and June 2006, 870 patients with primary lung cancer were surgically treated. Fifty-six (6.4%) of 870 patients had complications with idiopathic pulmonary fibrosis, and their data were retrospectively reviewed. There were 50 men and 6 women with an average age of 68 years. The incidence of squamous cell carcinoma was 28 (50.0%). Surgical procedures consisted of 7 wedge resections of the lung, 5 segmentectomies, 43 lobectomies, and 1 bilobectomy.

Results: Surgery-related hospital mortality was higher in patients with idiopathic pulmonary fibrosis than in patients without (7.1% vs 1.9%; P = .030). Four (7.1%) of these 56 patients had acute postoperative exacerbation of pulmonary fibrosis and died because of this complication. No factors such as pulmonary function, serologic data, operative data, and histopathologic data were considered predictive risk factors for the acute exacerbation. The postoperative 5-year survival for pathologic stage I lung cancer was 61.6% for patients with idiopathic pulmonary fibrosis and 83.0% for patients without (P = .019). The causes of late death were the recurrence of cancer or respiratory failure owing to idiopathic pulmonary fibrosis.

Conclusions: Although idiopathic pulmonary fibrosis causes high mortality after pulmonary resection for lung cancer and poor long-term survival, long-term survival is possible in patients with these two fatal diseases. Therefore, in selected patients, idiopathic pulmonary fibrosis may not be a contraindication to pulmonary resection for stage I lung cancer.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 

Earn CME credits at http://cme.ctsnetjournals.org

 

Idiopathic pulmonary fibrosis (IPF) is known to be concomitant with primary lung cancer (PLC) and sometimes causes catastrophic results after pulmonary resection. Acute postoperative exacerbation of IPF is one of the fatal complications after lung resection. Mortality after the occurrence of this complication is very high (80%–100%).^1,2Although some efforts have been made to establish the cause of acute postoperative exacerbation in order to prevent it,^3,4 the influence of the existence of IPF as a comorbidity on postoperative mortality, morbidity, and long-term survival after pulmonary resection for PLC has not been well studied. Hence, this study examines the implication of IPF on surgical results of pulmonary resection for PLC.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 
Patients
Between January 1994 and June 2006, 870 patients with PLC were surgically treated in our institute. Sixty-eight of 870 patients had complications with diffuse parenchymal lung disease. Ten patients with diffuse parenchymal lung disease and concomitant collagen diseases (rheumatoid arthritis in 3, Sjögren syndrome in 3, mixed collagen tissue diseases in 2, and progressive systemic sclerosis in 2) and 2 patients with nonspecific interstitial pneumonia were excluded from this study because these types of diffuse parenchymal lung diseases have different outcomes from IPF. Therefore, the inclusion criteria of this study were surgically treated patients with PLC concomitant with IPF (n = 56) and patients with PLC without diffuse parenchymal lung disease (n = 802). The medical records of 858 consecutive patients with PLC were retrospectively reviewed. Data acquisition and analysis were approved by our institutional review board. The records contained preoperative patient characteristics, disease status, operative procedures, pathologic diagnosis, and follow-up data. Idiopathic interstitial pneumonia was preoperatively diagnosed in all patients with IPF. This included 45 confident chest computed tomography diagnoses of IPF with consistent clinical features: fine crackles (resembling the sound of hook-and-loop fasteners) on chest auscultation and abnormalities, such as peripheral reticular opacity or honeycombing, on preoperative chest computed tomography. Furthermore, after surgery, idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) was definitively diagnosed in all patients with IPF by histopathologic assessment of the resected lung (architectural destruction, fibrosis often with honeycombing, scattered fibroblastic foci, patchy distribution, and involvement of the periphery of the acinus or lobule). The incidence of male sex, squamous cell carcinoma, wedge resection, and lower lobe tumor was higher in patients with IPF than in patients without. Furthermore, the percentage of diffusion capacity of the lung for carbon monoxide was higher in patients with IPF than in patients without. Patients with IPF underwent 7 wedge resections of the lung, 5 segmentectomies, 43 lobectomies, and 1 bilobectomy as surgical treatment for lung cancer. Pathologic stages were I in 28, II in 5, III in 14, and IV in 3 patients (Table 1 ).

Definition of Each Disorder
In this study, we used the criteria of acute exacerbation of IPF as described previously by Yoshimura and associates,⁵ namely, (1) intensified dyspnea, (2) increase in the interstitial shadow on chest radiograph, (3) increase in fine crackles on auscultation, (4) elevation of serum lactate dehydrogenase, and (5) decrease in arterial oxygen tension of more than 10 mm Hg under similar condition. Furthermore, we added the elevation of serum surfactant protein-D or sialylated carbohydrate antigen KL-6 to criterion 4. Diagnosis of acute exacerbation was confirmed if patients included all of 1, 2, and 3 plus at least either of 4 or 5 of the criteria.

Pneumonia was diagnosed by the presence of new and/or progressive pulmonary infiltrates on chest radiography plus two or more of the following criteria: fever (38°C), leukocytosis (12 x 10⁹/L), purulent sputum, or isolation of pathogen in respiratory secretions.

Regarding acute respiratory distress syndrome (ARDS), we used the American–European Consensus Conference Definition for acute respiratory distress syndrome.⁶

Perioperative and Postoperative Management
Chest radiographs were routinely taken on the first and third postoperative days and on the day after chest tube removal. Additional chest radiographs were taken, depending on the patients' clinical state, as opposed to including all symptoms and signs. If infiltrates were revealed on chest radiograph suggestive of ARDS or acute pulmonary embolism, high-resolution computed tomographic scan was performed for the differential diagnosis of these lung diseases.

Oxygen inhalation was administered at minimal level to maintain oxygen saturation at 92% or greater if patients did not have dyspnea or if they underwent any change in cardiorespiratory conditions owing to mild hypoxia.

The steroid pulse therapy with methylpredonisolone (1 or 2 g per day for 3 or 4 days as one course) was used as the first line treatment for acute postoperative exacerbation of IPF. In this series, neither immunosuppressive agent nor nitric oxide inhalation therapy was used.

Statistical Analysis
Statistical evaluation was performed by standard computer software (SPSS 9.0; SPSS, Inc, Chicago, Ill). All data are presented as mean ± standard deviation. Differences in continuous and categorical values were tested by unpaired the Student t test and ² square test (or Fisher's exact test), respectively. To account for the risk factor of morbidity or mortality after pulmonary resection for lung cancer, we used the logistic regression analysis. Furthermore, to account for the risk factor of late death after operation for patients with PLC in combination with IPF, we used the Cox proportional hazard model. Clinicopathologic related factors were quantified by univariate analysis and then all factors with P < .10 in the univariate analysis were included in the multivariate Cox hazard model together.

	Results

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 
Acute postoperative exacerbation of IPF, ARDS, and the need for prolonged mechanical ventilatory assist (> 2 days) for respiratory failure were more common in the patients with IPF than in those without (Table 2 ). IPF was a risk factor for causing these postoperative respiratory complications.

The percentage of diffusion capacity of the lung for carbon monoxide showed no differences between patients with the exacerbation and patients without it. No patient who underwent wedge resection of the lung had an exacerbation after the operation. There were no differences in the other values of pulmonary function, serologic data, operative factors, and histopathologic factors between the two groups (Table 3 ).

Survival
In patients undergoing surgical treatment for pathologic stage I PLC, actuarial survival curve and recurrence-free survival curve were compared between patients with IPF (n = 28) and patients without IPF (n = 526). Actuarial 5-year survival was 83.0% and 61.6% in patients without IPF and patients with IPF, respectively. Actuarial survival was significantly worse in patients with IPF than in patients without IPF (P = .0189) (Figure 1 ).

View larger version (13K): [in this window] [in a new window]   Figure 1. Actuarial cumulative survival curve in patients with pathologic stage I lung cancer. UIP, Usual interstitial pneumonia.

View larger version (15K): [in this window] [in a new window]   Figure 2. Actuarial cumulative disease-free survival curve in patients with pathologic stage I lung cancer. UIP, Usual interstitial pneumonia.

Limited resection for patients with PLC concomitant with IPF has no effect on the late outcome after surgical treatment. The 5-year survival of limited resection compared with lobectomy, the survival of wedge resection, segmentectomy, and lobectomy, were 62.4%, 50.0%, and 53.6 %, respectively (P = .93).

Sixteen of 52 patients in whom acute postoperative exacerbation of IPF did not develop immediately after operation died of exacerbation of pulmonary fibrosis (PF) (n = 5), recurrence of lung cancer (n = 8), bacterial pneumonia (n = 2), and cerebral infarction (n = 1) in late term after lung resection. Table 5 shows the comparison between patients with late death and patients without. The frequencies of cancer recurrence and late exacerbation of PF were higher in patients with late death than in patients without.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

There are reports that the incidence of lung cancer is increased in patients with IPF and that this effect is independent of the effect of cigarette smoking¹⁰ or mutations of the p-53 gene.¹¹ However, other studies did not show an increased risk of lung cancer.^12,13 Another possible mechanism for the development of lung cancer is carcinogenesis caused by PF through the promotion of atypical epithelial proliferation.¹⁴ Mizushima and associates¹⁵ reported that 154 (3.12%) of 4931 patients with lung cancer from 1975 to 1977 in Japan were associated with IPF: 23 patients with synchronous multiple lung cancer and 131 with single lung cancer. In these 154 patients, most tumors were observed in male patients, smokers, and in peripheral regions of the lung. Occurrence in the lower lobes, where a fibrotic shadow was prominent, was significantly more prevalent in the IPF–lung cancer groups than for the whole lung cancer group. The distribution of histologic types in the IPF–single lung cancer group was similar to that of the whole lung cancer group.

Operative mortality is considered to be higher in patients with PF than in control patients (17% vs 3.1%; P < .01) and there is a higher procedure-specific mortality in PF for pneumonectomy (33% vs 5.1%; P < .01) and lobectomy (12% vs 2.6%; P < .01).¹⁶

In the recent study,⁴ the long-term survival of patients who had lung cancer resection appears to be unaffected by the association with interstitial lung disease. They described that this reason could be explained by an adequate preoperative selection based on pulmonary function tests and a preferential choice for lobectomies. Thus, surgical resection should be offered to properly selected patients with lung cancer and underlying interstitial lung disease. Okamoto and associates² described that in patients with lung cancer concomitant with IPF, the actuarial 2-year survival after pulmonary resection was 52% overall, 58% for patients with N0 or N1 disease and 25% for those with N2 disease; the long-term results were poor partly because of the high incidence of a second PLC and partly because of the poor natural history of IPF. In our series, actuarial survival in patients with pathologic N0 disease was 61.6%. Recurrence or second development of the lung cancer is very common in these patients; therefore, these patients require intensive surveillance even after curative pulmonary resection for lung cancer. In addition, the postoperative mortality of lung resection for lung cancer concomitant with IPF is very high in comparison with that for simple lung cancer because of acute exacerbation of IPF. The long-term outcomes are poor because of the high incidence of second lung cancer and because of the deterioration of IPF itself. However, the poor results do not directly mean that surgical treatment for lung cancer concomitant with IPF should be limited or avoided, because the natural history of patients with lung cancer concomitant with IPF has not been clarified yet. Of course, we should exclude patients with lung cancer and IPF from the criteria for pulmonary resection if the survival is higher in patients without pulmonary resection than patients with, because the postoperative 5-year survival (61.6%) for patients with stage I primary lung cancer concomitant with IPF was similar to the relative 5-year survival (63.7%)⁷ of patients with IPF after the diagnosis from the census data. A randomized controlled trial is necessary to compare the survival after surgical treatment for lung cancer with IPF versus nonsurgical treatment.

In this study, as described previously by Yoshimura and associates,⁵ acute deterioration of interstitial lung disease immediately after lung resection in these patients was defined as acute postoperative exacerbation of IPF.

Few reports^1,2,5 have been published on acute exacerbation of IPF after lung resection for patients with PLC concomitant with IPF. Surprisingly, most of these were reported from Japan. The clinical concept of acute exacerbation of IPF has not been accepted in other countries because of lack of studies on it. Okamoto and associates² reported that postoperative exacerbation was observed in 4 (20%) of 20 patients who had IPF before surgery for PLC, and 3 of the 4 patients died. Furthermore, a higher incidence of idiopathic pulmonary exacerbation of IPF was observed in patients who had undergone lobectomy and pneumonectomy. Koizumi and associates¹ reported that exertional dyspnea (Hugh–Jones classification) greater than grade II, serum C-reactive protein greater than 2.0 mg/dL, serum lactate dehydrogenase greater than 400 IU/L, and percentage of total lung capacity less than 95% were considered to be preoperative risk factors of acute exacerbation and that methods to approach the thorax, such as posterolateral thoracotomy, muscle-sparing thoracotomy, and video-assisted thoracic surgry, did not pose an effect on the development of exacerbation of IPF. Kushibe and associates¹⁷ also reported that patients with IPF who had postoperative acute lung injury/ARDS had a significantly lower preoperative percent forced VC than those without such complications. Our results showed that no clinical factors were implicated on acute exacerbation. Even serum C-reactive protein or lactate dehydrogenase did not relate to the development of the exacerbation. That is why the patients with active phase IPF were excluded from our inclusion criteria for surgical resection.

Low oxygen inhalation, use of steroids,¹⁸ limited surgery,² avoidance of hyperinflation of the lung during operation, and prevention of postoperative pneumonia by the use of prophylactic antibiotic therapy have been used to prevent acute exacerbation of IPF after lung resection. However, none of these therapies presents any definitive evidence that one could prevent the development of the postoperative exacerbation of IPF. At the cellular level, IPF/UIP may in part be an oxidant-mediated disease,¹⁹ and oxygen therapy might be expected to increase tissue concentrations of toxic oxygen radicals.²⁰

Alveolar fluid is severely depleted in bronchoalveolar fluid from patients with IPF/UIP, and antioxidant therapy with N-acetylcysteine has been reported to improve the concentration of glutathione in the bronchoalveolar fluid of patients with IPF/UIP.²¹ Recent study revealed the following findings: (1) Lung re-expansion after one-lung ventilation (OLV) provoked severe oxidative stress. (2) The degree of generated oxygen-derived free radicals was associated with the duration of OLV. (3) Patients with lung cancer had a higher production of oxygen-derived free radicals than the normal population. (4) Tumor resection removes a large oxidative burden from the organism. (5) Mechanical ventilation and surgical trauma are weak free radical generators. (6) Manipulated lung tissue is also a source of oxygen-derived free radicals, not only intraoperatively but also for several hours later.²² These results indicate that shortening OLV duration and avoiding manipulation of lung tissue may inhibit the occurrence of the acute postoperative exacerbation of IPF resulting from oxygen-derived free radicals. However, it is very hard to strike a balance between shortening OLV duration and avoiding the manipulation clinically.

Only steroid pulse therapy has been considered for the treatment of acute postoperative exacerbation of IPF, but we were able to save none of 4 patients who had the exacerbation of IPF. Although there are some reports that second line therapies, such as immunosuppressant^23,24 and nitric oxide therapy,²⁵ prolonged survival, further study on these therapies is required.

There have been no reports on pulmonary function after lung resection for lung cancer in patients with IPF. Our data show that patients with IPF lost more VC and FEV_1.0 after lower lobectomy than patients without. They have proceeded with daily life at a lower pulmonary function than the postoperative predictive value. In patients with lung cancer concomitant with IPF, it is very important to estimate postoperative lung function, but it is very difficult to do so for lack of a predictive formula. We must emphasize that the conventional formula of each postoperative predictive VC or FEV_1.0 overestimates the true postoperative values even after lower lobectomy, which relatively preserves postoperative pulmonary function because residual upper lobe injury resulting from IPF is lesser than in the lower lobe injury.

Strategy for Recurrence or Second Development of Lung Cancer
In patients with PLC and IPF, it was very difficult to undergo reresection because their pulmonary function is lower than at the first operation. In our series, only 1 patient underwent reresection of the lung. On one hand, chemotherapy and/or radiotherapy²⁶ could possibly contribute to the development of PF. It is considered that single administration of platina agents, such as cisplatin and carboplatin, hardly induce pulmonary injury²⁷; however, vindesine and etoposide,²⁸ which are usually used together with cisplatin, or a single administration of any of them induces fatal pulmonary injury. When using these agents, one should take extremely good care of the patients with IPF.

Limitations of this Study
A number of limitations are inherent in a retrospective single institution study. A retrospective analysis is susceptible to various sources of bias that may not have been identified and controlled. At occurrence of the acute exacerbation of IPF after lung resection for lung cancer concomitant with IPF, adjuvant therapy added to steroid pulse therapy is not determined, and at the lung cancer recurrence after lung resection, we do not have definitive strategy. Only 4 patients underwent acute exacerbation of IPF, in which the case number might have been too little to predict some risk factor for the development of the exacerbation.

Another limitation of the present study is the long time period of the analysis (about 11 years) wherein the surgical techniques (video-assisted thoracic surgery is predominant in late term of study period) and perioperative management differ. After 1999, we routinely administrated erythromycin (300 mg per day) or clarythromycin (400 mg per day) for patients with lung cancer who had complications with IPF, in which the administration period was between 1 week preoperatively and 3 or 4 weeks postoperatively.

A further limitation may be the definition of acute postoperative exacerbation of IPF. We could not distinguished acute postoperative exacerbation of IPF from acute interstitial pneumonia. We cannot deny that there could be two diseases occurring together or as a single disease entity in this study.

	Conclusions

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 
Our retrospective data reveal the following implications: (1) Acute postoperative exacerbation of IPF causes high mortality. (2) It is very difficult to predict the occurrence of the postoperative exacerbation of IPF. (3) Although the long-term results of surgical treatment for lung cancer concomitant with IPF are worse than that without IPF, the surgical treatment of the PLC is effective in patients with stage I lung cancer with concomitant IPF.

	Table E1

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 

Summary of patients who had postoperative acute exacerbation of IPF

Case, sex, age (y) Procedure P-stage Onset (POD) SPT (No. of times) Concomitant disease SP-D/LDH ([IU/L]/[ng/dL]) POS 1, M, 68 LLL 1B 7, 27 2 BPn (Klebsiela) 1099/1120 42 2, M, 61 LUL 3B 5 2 BPn (MRSA, PA) 850/1112 13 3, F, 74 RUL 3B 3, 24 3 Bpn (MSSA, PA) 1342/1842 32 4, M, 72 LLL 2B 6 1 — NA /1206 9

IPF, Idiopathic pulmonary fibrosis; P-stage, pathologic stage; POD, postoperative day; SPT, steroid pulse therapy for exacerbation of IPF; SP-D, surfactant protein-D; LDH, lactate dehydrogenase; POS, postoperative survival; M, male; F, female; LLL, left lower lobectomy; LUL, left upper lobectomy; RUL, right upper lobectomy; Bpn, bacterial pneumonia; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; PA, Pseudomonas aeruginosa, NA, not available.

	Table E2

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 

Pulmonary function in lower lobectomy cases

Variables IPF (–) (n = 250) IPF (+) (n = 36) P value Preop VC (L) 3.22 ± 0.79 3.29 ± 0.71 .710 Postop VC (L) 2.55 ± 0.77 2.25 ± 0.64 .270 Preop FEV1.0 (L) 2.39 ± 0.68 2.35 ± 0.57 .800 Postop FEV1.0 (L) 1.99 ± 0.61 1.67 ± 0.42 .122 Postop VC/preop VC (%) 78.3 ± 15.1 67.0 ± 12.1 .038 Postop FEV1.0/preop FEV1.0 (%) 81.3 ± 13.5 67.7 ± 10.6 .006

Preop, Preoperative; Postop, postoperative; VC, vital capacity; FEV_1.0, forced expiratory volume in 1 second.

	References

Top Abstract Introduction Patients and Methods Results Discussion Conclusions Table E1 Table E2 References

 

1. Koizumi K, Hirata T, Hirai K, Mikami I, Okada D, Yamagishi S, et al. Surgical treatment of lung cancer combined with interstitial pneumonia: the effect of surgical approach on postoperative acute exacerbation. Ann Thorac Cardiovasc Surg 2004;10:340-346.[Medline]
   
2. Okamoto T, Gotoh M, Masuya D, Nakashima T, Liu D, Kameyama K, et al. Clinical analysis of interstitial pneumonia after surgery for lung cancer. Jpn J Thorac Cardiovasc Surg 2004;52:323-329.[Medline]
   
3. Utz JP, Ryu JH, Douglas WW, Hartman TE, Tazelaar HD, Myers JL, et al. High short-term mortality following lung biopsy for usual interstitial pneumonia. Eur Respir J 2001;17:175-179.[Abstract/Free Full Text]
   
4. Martinod E, Azorin JF, Sadoun D, Destable, MD, Le Toumelin P, Longchampt E, et al. Surgical resection of lung cancer in patients with underlying interstitial lung disease. Ann Thorac Surg 2002;74:1004-1007.[Abstract/Free Full Text]
   
5. Yoshimura K, Nakatani T, Nakamori Y, Chonabayashi N, Tachibana A, Nakata K, et al. [Acute exacerbation in idiopathic interstitial pneumonia.]. Nihon Kyobu Shikkan Gakkai Zasshi 1984;22:1012-1020In Japanese.[Medline]
   
6. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American–European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-824.[Abstract/Free Full Text]
   
7. Schwartz DA, Helmers RA, Galvin JR, Van Fossen DS, Frees KL, Dayton CS, et al. Determinants of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1994;149:450-454.[Abstract/Free Full Text]
   
8. Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. Chest 1998;113:396-400.[Medline]
   
9. Mapel DW, Hunt WC, Utton R, Baumgartner KB, Samet JM, Coultas DB. Related idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts. Thorax 1998;53:469-476.[Abstract/Free Full Text]
   
10. Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med 2000;161:5-8.[Abstract/Free Full Text]
    
11. Hojo S, Fujita J, Yamadori I, Kamei T, Yoshinouchi T, Ohtsuki Y, et al. Heterogeneous point mutations of the p53 gene in pulmonary fibrosis. Eur Respir J 1998;12:1404-1408.[Abstract]
    
12. Mapel DW, Hunt WC, Utton R, Baumgartner KB, Samet JM, Coultas DB. Idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts. Thorax 1998;53:469-476.[Abstract/Free Full Text]
    
13. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199-203.[Medline]
    
14. Meyer EC, Liebow AA. Relationship of interstitial pneumonia honeycombing and atypical epithelial proliferation to cancer of the lung. Cancer 1965;18:322-351.[Medline]
    
15. Mizushima Y, Kobayashi M. Clinical characteristics of synchronous multiple lung cancer associated with idiopathic pulmonary fibrosis. A review of Japanese cases. Chest 1995;108:1272-1277.[Medline]
    
16. Kumar P, Goldstraw P, Yamada K, Nicholson AG, Wells AU, Hansell DM, et al. Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection. J Thorac Cardiovasc Surg 2003;125:1321-1327.[Abstract/Free Full Text]
    
17. Kushibe K, Kawaguchi T, Takahama M, Kimura M, Tojo T, Taniguchi S. Operative indications for lung cancer with idiopathic pulmonary fibrosis. Thorac Cardiovasc Surg 2007;55:505-508.[Medline]
    
18. Yano T, Koga T. [Prophylactic administration of steroid for interstitial pneumonia after pulmonary resection for lung cancer.]. Kyobu Geka 2005;58:37-40In Japanese.[Medline]
    
19. Hunninghake GW, Kalica AR. Approaches to the treatment of pulmonary fibrosis. Am J Respir Crit Care Med 1995;151:915-918.[Abstract]
    
20. Douglas WW, Ryu JH, Schroeder DR. Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival. Am J Respir Crit Care Med 2000;161:1172-1178.[Abstract/Free Full Text]
    
21. Meyer A, Buhl R, Magnussen H. The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. Eur Respir J 1994;7:431-436.[Abstract]
    
22. Misthos P, Katsaragakis S, Milingos N, Kakaris S, Sepsas E, Athanassiadi K, et al. Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation. Eur J Cardiothorac Surg 2005;27:379-383.[Abstract/Free Full Text]
    
23. Sakamoto S, Homma S, Kawabata M, Kono T, Seki K, Nakata K, et al. [Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer.]. Nihon Kokyuki Gakkai Zasshi 2004;42:760-766In Japanese.[Medline]
    
24. Inase N, Sawada M, Ohtani Y, Miyake S, Isogai S, Sakashita H, et al. Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid. Intern Med 2003;42:565-570.[Medline]
    
25. Yoshida M, Taguchi O, Gabazza EC, Yasui H, Kobayashi T, Kobayashi H, et al. The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis. Eur Respir J 1997;10:2051-2054.[Abstract]
    
26. Takeuchi E, Yamaguchi T, Mori M, Tanaka S, Nakagawa M, Yokota S, et al. [Characteristics and management of patients with lung cancer and idiopathic interstitial pneumonia.]. Nihon Kyobu Shikkan Gakkai Zasshi 1996;34:653-658In Japanese.[Medline]
    
27. Chang AY, Kuebler JP, Tormey DC, Anderson S, Pandya KJ, Borden EC, et al. Phase II evaluation of a combination of mitomycin C, vincristine, and cisplatin in advanced non–small cell lung cancer. Cancer 1986;57:54-59.[Medline]
    
28. Dajczman E, Srolovitz H, Kreisman H, Frank H. Fatal pulmonary toxicity following oral etoposide therapy. Lung Cancer 1995;12:81-86.[Medline]
    

This article has been cited by other articles:

				Y. Saito, Y. Kawai, N. Takahashi, T. Ikeya, K. Murai, Y. Kawabata, and E. Hoshi Survival After Surgery for Pathologic Stage IA Non-Small Cell Lung Cancer Associated With Idiopathic Pulmonary Fibrosis Ann. Thorac. Surg., November 1, 2011; 92(5): 1812 - 1817. [Abstract] [Full Text] [PDF]

				A. Watanabe Invited Commentary Ann. Thorac. Surg., November 1, 2011; 92(5): 1817 - 1818. [Full Text] [PDF]

				M. Kashima, K. Yamakado, H. Takaki, H. Kodama, T. Yamada, J. Uraki, and A. Nakatsuka Complications After 1000 Lung Radiofrequency Ablation Sessions in 420 Patients: A Single Center's Experiences Am. J. Roentgenol., October 1, 2011; 197(4): W576 - W580. [Abstract] [Full Text] [PDF]

				C. R. Lloyd, S. L. F. Walsh, and D. M. Hansell High-resolution CT of complications of idiopathic fibrotic lung disease Br. J. Radiol., July 1, 2011; 84(1003): 581 - 592. [Abstract] [Full Text] [PDF]

				M. Kanzaki, T. Kikkawa, H. Maeda, M. Kondo, T. Isaka, T. Shimizu, M. Murasugi, and T. Onuki Acute exacerbation of idiopathic interstitial pneumonias after surgical resection of lung cancer Interact CardioVasc Thorac Surg, June 1, 2011; 13(1): 16 - 20. [Abstract] [Full Text] [PDF]

				H. Ito, H. Nakayama, M. Tsuboi, Y. Kameda, T. Yokose, C. Hasegawa, and K. Yamada Subpleural Honeycombing on High Resolution Computed Tomography is Risk Factor for Fatal Pneumonitis Ann. Thorac. Surg., March 1, 2011; 91(3): 874 - 878. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Atsushi Watanabe Tetsuya Higami Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, A. Articles by Mawatari, T. Search for Related Content PubMed Articles by Watanabe, A. Articles by Mawatari, T. Related Collections Lung - cancer Lung - other