ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Hyun-Sung Lee
Moon Soo Kim
Jong Mog Lee
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Song, S.-W.
Right arrow Articles by Zo, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, S.-W.
Right arrow Articles by Zo, J. I.
Related Collections
Right arrow Lung - other

Ann Thorac Surg 2006;81:1974-1981
© 2006 The Society of Thoracic Surgeons

Original article: General thoracic

Preoperative Serum Fibrinogen Level Predicts Postoperative Pulmonary Complications After Lung Cancer Resection

Suk-Won Song, MD, Hyun-Sung Lee, MD, Moon Soo Kim, MD, Jong Mog Lee, MD, Jee Hee Kim, MD, Byung-Ho Nam, PhD, Jae Ill Zo, MD, PhD *

Center for Lung Cancer, Cancer Biostatistics Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea

Accepted for publication January 3, 2006.

* Address correspondence to Dr Zo, Center for Lung Cancer, National Cancer Center, 809 Madu1-dong, Ilsandong-gu, Goyang, Gyeonggi, 411-769, Korea (Email: jaylzo{at}ncc.re.kr).

Presented at the Poster Session of the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Patients undergoing pulmonary resection are thought to be at high risk for the development of postoperative pulmonary complications (PPCs), and these complications may lead to serious morbidity. The purpose of this study was to identify the factors associated with postoperative pulmonary complications in patients undergoing lung cancer resection and to determine the effect of PPCs on survival.

METHODS: The study involved a retrospective review of 635 patients who had undergone curative resection for lung cancer. The patient group included 504 males (79.4%), and the overall mean age was 61.3 years. Patients were classified as those who had experienced PPCs (PPCs group, n = 105, 16.5%) or those who had not (no-PPCs group, n = 530, 83.5%).

RESULTS: The surgical procedures performed were 101 pneumonectomies (15.9%), 505 lobectomies (79.5%), and 29 lesser resections (4.6%). Cancer types comprised 330 squamous cell carcinomas (52.0%), 255 adenocarcinomas (40.2%) and 50 others (7.8%). Univariate analysis showed that the following factors were predictors for PPCs: male sex, erythrocyte sedimentation rate, preoperative serum fibrinogen level, pulmonary function, chronic obstructive pulmonary disease, smoking, double primary cancer, and surgical duration. Multivariate logistic regression showed that preoperative serum fibrinogen level (p < 0.001), surgical duration (p < 0.0001) and being male (p = 0.02) were significant predictors of PPCs. Overall survival 3 years after surgery was 68.2% in no-PPCs group and 38.8% in PPCs group (p < 0.0001). Regardless of tumor staging, overall survival differed significantly between PPCs and no-PPCs groups, whereas disease-free survival did not.

CONCLUSIONS: Higher preoperative serum fibrinogen levels, longer surgical duration, and being male were the predictive factors for PPCs in surgical candidates. The development of PPCs was linked to a shortened overall survival.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Patients undergoing thoracotomy associated with lung resection are thought to be at high risk for the development of postoperative pulmonary complications (PPCs) during the perioperative period, and these complications may lead to serious morbidity [1–5]. Despite advances in surgical techniques, perioperative care, and anesthesia, the mortality rate ranges from 2% to 12% after lung resection [6, 7]. Although surgical mortality after lobectomy or pneumonectomy has decreased over the past decade, PPCs continue to occur at rates as high as 49% [8]. Postoperative pulmonary complications after lung resection result in increased in-hospital stay, increased surgical mortality rate, and increased cost of hospitalization.

Various clinical research designs and definitions have identified numerous patient- or procedure-related risk factors for PPCs after pulmonary resection. In most but not all studies, the frequently identified risk factors were being male, being of an older age [6, 7, 9, 10], undergoing a relatively large extent of surgical resection [11], having reduced preoperative pulmonary function [8, 9], having cardiovascular comorbidity [6, 8, 12], and being a smoker [8, 10].

The present study examined PPCs in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection. We examined the incidence and clinical implications of PPCs, identified the preoperative and intraoperative factors that may predispose PPC development, and examined the effect of PPCs on survival.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
The study involved a retrospective review of 635 patients who had undergone lung resection in a curative intent for NSCLC at the Center for Lung Cancer, National Cancer Center, Korea, between March 2001 and October 2004. We obtained the informed consents from the patients and next of kin for the usage of the clinical and serologic data with operation permission. Patients were divided into two groups; the PPCs group (n = 105, 16.5%) were patients with evidence of PPCs and the no-PPCs group (n = 530) were those showing no evidence of PPCs. Each patient was assessed in terms of general preoperative factors, surgical factors, and oncologic factors (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Characteristics of Patients With and Without Postoperative Pulmonary Complications
 
Preoperative General Factors
Before surgery, patients underwent the predefined routine evaluation work-ups that include chest roentgenogram, chest and abdominal computed tomography scanning, radionuclide bone scan, brain magnetic resonance imaging, and fibroptic bronchoscopy.

Routine blood tests and preoperative evaluation for pulmonary function test were performed. Preoperative serum fibrinogen levels were determined using the Clauss method with thrombin as the reagent with normal range of 200 to 400 mg/dL.

Surgical Factors
All surgical procedures were performed under general anesthesia. Thiopental sodium (5 to 6 mg/kg intravenously [IV]) was used for induction. Orotracheal intubation was facilitated by 0.15 mg/kg IV vecuronium. Anesthesia was maintained using 50% N2O in oxygen and enflurane (1.0 to 1.5 minimum alveolar concentration). At the completion of surgery, the neuromuscular block was reversed using 15 mg IV pyridostigmine preceded by 0.4 mg IV glycopyrrolate. Left-sided double-lumen endotracheal tubes were used during surgical procedures. A posterolateral thoracotomy through the fifth intercostal space was accomplished while patients were under general anesthesia and in the lateral decubitus position. Routine systematic lymphadenectomy of hilar and mediastinal lymph nodes was performed in all cases.

Oncologic Factors
After careful examination of all resected tumor and lymph node specimens, pathologic TNM stage was rendered for each case. Preoperative and postoperative serum carcinoembryonic antigen levels were determined.

Definitions of Postoperative Pulmonary Complications
Only postoperative pulmonary complications (PPCs) occurring within 30 days of lung resection were included.

Acute respiratory distress syndrome was defined as (1) acute onset with a PaO2/fraction of inspired oxygen of 200 mm Hg or less. (2) Bilateral infiltrates: the infiltrates may be patchy, diffuse, homogeneous, or asymmetrical, and should be consistent with pulmonary edema or fibrotic changes associated with fibroproliferation. Opacity due to pleural effusions or atelectasis should not be considered. Unilateral infiltrate was included for pneumonectomy patients. (3) No evidence of left atrial hypertension. If measured, a pulmonary artery wedge pressure must be 18 mm Hg or less. (4) The three previously cited criteria must occur together within a 24-hour interval [13, 14].

Acute lung injury was defined as (1) acute onset with a PaO2/fraction of inspired oxygen of 300 mm Hg or less; (2) bilateral infiltrates; (3) no evidence of left atrial hypertension. If measured, a pulmonary artery wedge pressure of 18 mm Hg or less.

For pulmonary infection, (1) pneumonia was diagnosed on the basis of a compatible chest radiograph and purulent sputum with Gram's stain and sputum culture documenting the presence of microorganisms; (2) aspiration pneumonitis was defined as either the presence of bilious secretion or particulate matter in the tracheobronchial tree, or, in patients who did not have their tracheobronchial airways directly examined after regurgitation, a postoperative chest radiograph with infiltrates not identified on a preoperative radiograph; (3) bronchopleural fistula; (4) empyema and related findings.

Sputum retention was defined as inability to adequately clear the tracheobroncheal secretions with standard physiotherapy, which was coincided with lobar or whole-lung atelectasis based on chest radiography requiring aspiration bronchoscopy. The diagnosis was essentially clinical, characterized by evidence of respiratory distress with rapid, shallow, and bubbly respirations.

Prolonged air leak was defined as an air leak requiring more than 2 weeks of postoperative chest tube drainage and two times of chemical pleurodesis.

Bronchospasm was defined as a condition of respiratory dysfunction characterized by evidence of severe wheezing or a prolonged expiratory phase requiring aminophylline loading, aerosolized bronchodilator, beta agonist, and steroid therapy.

Postoperative Evaluation
Unless otherwise indicated, all patients underwent extubation in the operating room at the completion of surgery. All patients were managed in the intensive care unit for one night. Postoperative pain control was achieved using epidural analgesia for several postoperative days and thereafter changed to oral analgesics. Emphasis was placed on aggressive pulmonary care, early ambulation, and pain control to minimize PPCs.

Statistical Analysis
Data were analyzed using SPSS for Windows (version 11.0; SPSS, Chicago, Illinois). Categorical variables were compared using the {chi}2 test or Fisher's exact test, and continuous variables were compared using Student's t or Mann-Whitney U tests where appropriate. The risk of PPCs associated with selected factors was evaluated using stepwise binary logistic regression analysis to estimate odds ratios (OR) and their 95% confidence intervals (CI). Continuous variables were dichotomized using the median or extreme values over the normal range as the cutoff value. A p value of 0.05 or less according to univariate analysis was chosen as the criterion for submitting variables to the model. Goodness of fit was assessed using the Hosmer and Lemeshow {chi}2 test. The relative risk, defined as the ratio of incidence among exposed to that among nonexposed subjects, was used to summarize the strength of the association between risk factors and pulmonary complications; the 95% CIs of the relative risk were calculated using Miettinen's test-based approach. Unless otherwise stated, results are expressed as mean ± SD for continuous variables, and as a percent for categorical variables. Survival curves were computed according to the methods of Kaplan-Meier.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Study Population
Six hundred and thirty-five patients (mean age, 61.3 ± 8.8 years; range, 25 to 85; 504 men and 131 women) who underwent pulmonary resections for non-small cell lung cancer are the subject of this analysis. Fifty-nine patients (9.3%) received neoadjuvant chemotherapy, and 47 (7.4%) had previous malignancies or double primary cancers. There were 439 (69.1%) current or former smokers. Lobectomy, the most common operation, was performed in 505 cases (79.5%), including sleeve lobectomies in 55 (8.6%), whereas 101 patients (15.9%) underwent a pneumonectomy and 29 patients (4.6%) underwent a segmentectomy or lesser resection. Cancer types included squamous cell carcinoma in 330 patients (52.0%), adenocarcinoma including bronchioloalveolar cell carcinoma in 255 patients (40.2%), and other types in 50 patients (7.8%), including large cell carcinoma and sarcomatoid carcinoma. Pathology staging showed stage 0 (n = 3; 0.5%), stage IA (n = 76; 12.0%), stage IB (n = 178; 28.0%), stage IIA (n = 21; 3.3%), stage IIB (n = 90; 14.2%), stage IIIA (n = 199; 31.3%), stage IIIB (n = 38; 6.0%), and stage IV (n = 30; 4.7%) (Table 1).

Postoperative Pulmonary Complications
One hundred and five patients (16.5%) experienced at least one PPC. Sputum retention was the most prevalent complication (n = 36, 34.3%), followed by acute respiratory distress syndrome (n = 23, 21.9%), prolonged air leak (n = 18, 17.1%), pulmonary infection (n = 13, 12.4%), acute lung injury (n = 9, 8.6%), and bronchospasm (n = 6, 5.7%). There was no association between the PPC rate and any particular surgical procedure (Table 1).

Sputum retention after lung surgery is a potentially lethal condition, which can progress to atelectasis, pneumonia, and respiratory failure, requiring ventilator support if untreated at all. It occurs when a patient is incapable of adequately clearing tracheobronchial secretions, and aspiration bronchoscopy was performed as soon as possible.

Acute respiratory distress syndrome occurred on postoperative day 3.6 ± 2.5 (median 3). The duration of mechanical ventilation was 16.7 ± 24.9 days. Tracheostomies were performed in 12 patients (52.2%). The mean intensive care unit stay and hospital stay was 19.8 ± 24.6 days (median, 15; range, 0 to 120) and 39.9 ± 29.9 days (median, 30; range, 5 to 125), respectively. Surgical mortality due to acute respiratory distress syndrome occurred in 11 patients (47.8%). In acute respiratory distress syndrome patients, empyema thoracis occurred in 5 patients, bronchopleural fistula in 4 patients, and wound infection in 2 patients. Fifteen episodes (65.2%) of nosocomial pneumonia occurred during mechanical ventilation. Ten episodes of pneumonia were associated with methicillin-resistant Staphylococcus aureus, seven episodes were related to Pseudomonas aeruginosa, and four were related to Enterobacter species.

Prolonged air leak was diagnosed in 18 patients. The length of chest tube drainage was 16.1 ± 2.5 days (range, 14 to 22). They were treated more than twice with chemical pleurodesis with talc or doxycycline. One patient had an air leak lasting longer than 3 weeks. The length of hospital stay was 18.9 ± 8.0 days (range, 15 to 47).

Of the 13 pulmonary infections, 9 had sputum cultures positive for bacterial pneumonia, 3 empyema thoracis, and 1 bronchopleural fistula. Gram-negative bacilli were cultured in 7 of the 9 episodes of pneumonia (77.8%). The distribution pattern of Gram-negative bacilli-isolated strains was as follows: Pseudomonas aeruginosa (n = 4; 44.4%); Enterobacter cloacae (n = 4; 44.4%); Haemophilus influenzae (n = 1; 11.1); Klebsiella pneumoniae (n = 1; 11.1%); and others (Enterobacteriaceae sp, n = 1; 11.1%; and Acinetobacter baumannii, n = 4; 44.4%). One Candida and one Streptococcus pneumoniae infection were identified. Staphylococcus aureus was cultured in three episodes (all were methicillin-resistant). Four episodes were related to both Gram-negative bacilli and Gram-positive cocci.

Of the 9 acute lung injury patients, 4 were treated with steroid therapy and 1 patient required mechanical ventilation. Mean hospital stay was 20.5 ± 9.0 days (range, 11 to 38) without surgical mortality.

Risk Factors for Postoperative Pulmonary Complications
Thirty perioperative variables were examined for possible association with PPC development (Table 1). Univariate analysis showed the following 11 variables were associated with PPCs: sex, erythrocyte sedimentation rate, preoperative serum fibrinogen level, percent forced vital capacity (%FVC), percent forced expiratory volume in 1 second (%FEV1), forced expiratory volume in 1 second (FEV1), chronic obstructive pulmonary disease, total cigarette smoking (packs-years), smoking status, previous malignancy/double primary cancer, and surgical duration.

Stepwise forward binary logistic regression analysis identified three perioperative variables independently associated with PPCs: a preoperative serum fibrinogen level of 400 mg/dL or greater (OR, 6.80; 95% CI: 3.30–14.00; p < 0.0001), a surgical duration of 180 minutes or more (OR, 3.31; 95% CI: 1.73–6.34; p < 0.0001), and male sex (OR, 5.93; 95% CI: 1.32–26.73; p = 0.020; Table 2). Previous results were confirmed using stepwise backward binary logistic regression analysis. The {chi}2 value for this model was 6.401 for 11 degrees of freedom, indicating that the model was an acceptable fit for the data set. To examine the interaction between serum fibrinogen level and smoking exposure, we used the bivariate and partial correlation adjusted by sex. On bivariate correlation, correlation coefficient was 0.164 (p = 0.004). However, on partial correlation, coefficient controlling for sex, was 0.057 (p = 0.317). Although fibrinogen level and smoking exposure seemed to correlate well together, they were confounded by the factor "sex." Fibrinogen level and smoking exposure amounts were significantly higher in male sex. To evaluate the correlation between these variables and PPCs, we used the independent t test and logistic regression analysis stratified by smoking status and sex. Serum fibrinogen was deeply associated with the development of PPCs regardless of smoking status and sex (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 2. Multivariate Logistic Regression Analysis of Postoperative Pulmonary Complications
 

View this table:
[in this window]
[in a new window]
  		Table 3. Preoperative Serum Fibrinogen Level and Postoperative Pulmonary Complications Stratified by Smoking Status and Sex
 
Patient Outcomes
Seventeen deaths (2.68% mortality rate) occurred after surgery, with 11 occurring within 30 days (1.73%, 30-day mortality rate). Pneumonectomies, lobectomies, and wedge resections were all associated with similar in-hospital PPC rates (Table 1). The causes of surgical mortality were acute respiratory distress syndrome (n = 10), bacterial pneumonia (n = 3), invasive aspergillosis (n = 1), acute myocardial infarction (n = 1), sepsis (n = 1), and anaphylactic shock (n = 1). Of the factors studied, development of PPCs was the sole factor associated with an increased risk of death. The relative risk was 27.819 (95% CI: 7.900 to 97.965). Multivariate analysis was not performed to assess death as a dependent variable owing to the small number of cases. The mean duration of postoperative hospital stay was 12.6 ± 3.4 days for patients without PPCs and 25.1 ± 19.9 days for patients with PPCs (p < 0.0001).

Postoperative Pulmonary Complications and Survival
Follow-up was complete (mean follow-up, 16.9 ± 11.1 months; range, 0.3 to 43.4). Overall survival at 1 and 3 years was 92.1% and 68.2% in the no-PPCs group, and 76.9% and 38.8% in the PPCs group (Fig 1A; p < 0.0001, log-rank test; hazard ratio 2.67; 95% CI: 1.68–4.24). However, the groups did not differ in terms of disease-free survival at 1 and 3 years: at 76.0% and 60.2% in the no-PPCs group, and 70.6% and 56.2% in the PPCs group, respectively (Fig 1B; p = 0.232, log-rank test; hazard ratio 1.77; 95% CI: 0.99 to 3.15). Regardless of tumor staging, overall survival differed significantly between the PPCs and no-PPCs groups, while disease-free survival did not (Fig 2).


Figure 1
View larger version (19K):
[in this window]
[in a new window]
  		Fig 1. Survival of patients in the no–postoperative pulmonary complications (PPCs) group and the PPCs group. (A) Overall survival at 3 years was 68.2% in the no-PPCs group, and 38.8% in the PPCs group (p < 0.0001). (B) Disease-free survival at 3 years was 60.2% in the no-PPCs group, and 56.2% in the PPCs group (p = 0.232).

 

Figure 2
View larger version (34K):
[in this window]
[in a new window]
  		Fig 2. Survival of patients according to tumor stage in the no–postoperative pulmonary complications (PPCs) group and the PPCs group. (A) Overall survival at 1 and 3 years was, respectively, 94.8% and 81.9% in the no-PPCs group and 84.6% and 43.0% in the PPCs group in the early stage (stage I and II; p = 0.001). (B) Disease-free survival at 1 and 3 years was, respectively, 85.7% and 72.8% in the no-PPCs groups and 77.0% and 65.1% in the PPCs group in the early stage (stage I and II; p = 0.165). (C) Overall survival at 1 and 2 years was, respectively, 88.0% and 68.7% in the no-PPCs group and 66.5 and 32.8% in the PPCs group in the advanced stage (stage III and IV; p = 0.001). (D) Disease-free survival at 1 and 2 years was, respectively, 61.6% and 43.6% in the no-PPCs groups and 61.6 and 39.6% in the PPCs group in the advanced stage (stage III and IV; p = 0.621).

 
Seventy-six patients (14.9%) in the no-PPCs group and 24 patients (27.3%) in the PPCs group died during the follow-up period. The primary cause of death was recurrence of the primary lung cancer in both groups (69 patients in the no-PPCs and 14 in the PPCs group). In evaluating the causes of death of 599 patients who were discharged from the hospital, 9 (37.5%) of 24 patients who had PPCs died of causes unrelated to lung cancer: emaciation in 1, respiratory insufficiency in 7, and acute myocardial infarction in 1. Seven (9.2%) of 76 patients without PPCs succumbed to miscellaneous causes other than lung cancer: emaciation in 1, respiratory insufficiency in 2, and unknown in 4. Thus, patients who had PPCs died of unrelated causes to lung cancer more frequently than those without PPCs (p < 0.0001). The mortality rate due to cancer-unrelated causes is represented in Figure 3. There were fewer cases of respiratory failure in the no-PPCs group. In contrast, the incidence of respiratory failure leading to death constantly increased in the PPCs group. Most of the mortality due to respiratory insufficiency occurred especially within 1 year after discharge in the PPCs group.


Figure 3
View larger version (19K):
[in this window]
[in a new window]
  		Fig 3. Cumulative mortality during the follow-up from cancer-unrelated causes after lung resection in the no–postoperative pulmonary complications (PPCs) group and the PPCs group (p < 0.0001).

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
Pulmonary resection for lung cancer is associated with morbidity rates between 12% and 49% and mortality rates between 2% and 12 % [6, 7]. In addition to defining the clinical stage of the lung cancer, preoperative evaluation seeks to determine the risk of planned surgery. For this reason, accurate prediction of the complication risk after resection surgery in patients with NSCLC is a very important issue. Since patients with lung cancer who undergo evaluation for lung resection are usually smokers, they often have concomitant chronic obstructive pulmonary disease with impaired lung function, making them at increased risk for development of PPCs. Therefore, in addition to tumor stage evaluation and histologic analysis, physiologic assessment of these patients is very important. Previous reports have identified a wide variety of factors associated with overall morbidity and mortality after lung resection [6–12].

The present study shows that an increased level of serum fibrinogen is a predictor for the development of PPCs. Previous studies have shown that plasma fibrinogen level is an independent and major risk factor for acute coronary events or stroke and correlates well with the presence and severity of coronary artery disease, suggesting that fibrinogen is involved in the progression of atherosclerosis in the coronary artery disease as well as peripheral artery occlusive disease [15, 16]. Fibrinogen, an acute phase reactant and blood clotting factor, is synthesized by hepatocytes and released in large amounts into the circulation primarily in response to interleukin-6 stimulation in systemic inflammation [17, 18]. However, fibrinogen is also synthesized by lung epithelium in cases of ongoing airway inflammation and lung tissue destruction [17, 18]. Elevated serum fibrinogen can affect coagulability, blood viscosity and rheology, platelet aggregation, and endothelial function [19], which may induce microthrombosis in the pulmonary capillaries and ischemic changes in the lung tissues, and make patients vulnerable to ischemia, inflammation, and infection, especially after lung resection. Therefore, it may be that measurement of serum fibrinogen levels provides a noninvasive method of identifying ongoing airway inflammation and lung tissue destruction [16, 17]. Fibrinogen is also associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. The dramatic upregulation of fibrinogen in response to inflammatory stimuli suggests that it may contribute to pathophysiologic events associated with fibrotic lung disease. Plasma proteins such as fibrinogen can decrease the activity of surfactant in acute respiratory distress syndrome as levels of surfactant drop concomitantly with disease progression [20].

The present results suggest preoperative preexisting local lung inflammatory process is a risk factor for PPCs development. Numerous studies have demonstrated coagulation and fibrinolysis disorders in cancer patients [21, 22]. Levels of basic hemostatic markers including platelets, prothrombin time, activated partial thrombin time, fibrinogen, D-dimer. and antithrombin III are elevated in lung cancer patients [23, 24]. The mechanisms activating coagulation and fibrinolysis systems differ between NSCLC and small-cell lung cancer (SCLC) [25]. In SCLC, tumor cells release tissue factor that directly activates the coagulation system, whereas in NSCLC, host macrophages release procoagulant factors that activate the fibrinolytic system [25, 26].

The present study found that the preoperative serum fibrinogen level was linearly associated with the pathologic T stage (p < 0.05, data not shown). Some authors report that inflammatory mediators are positively correlated with the tumor stage and survival.

In addition to the preoperative serum fibrinogen level, prolonged surgery and being male were predictive factors for PPCs. Longer surgical duration is considered to be related to increased surgical stress, which can lead to enhanced accumulation of water and sodium in the third space during surgery and increased extravascular lung water, causing a ventilation-perfusion mismatch in the lung. A longer operation time can therefore result in a higher PPC incidence and subsequent in-hospital mortality. Longer surgical time is often due to more locally advanced lung cancers that invade the chest wall, diaphragm, mediastinal pleura, and other neighboring structures, and emphysematous lung disease, which is characterized by severe pleural adhesions, incomplete fissures, and air leak during manipulation or adhesiolysis. The higher incidence of PPCs among males than females is believed to be associated with larger amount of smoking exposure (37.4 ± 26.7 pack-years for males and 3.2 ± 10.2 pack-years for females), smoking status (former and current smoker: 444 of 504 males [88.1%] and 16 of 131 females [12.2%]), and comorbidity of chronic obstructive pulmonary disease with impaired lung function (133 of 486 males [27.4%] and 7 of 129 females [5.4%]). The interaction between multiple variables and PPCs seems to be tangled. However, Table 3 suggests that preoperative serum fibrinogen is deeply associated with the development of postoperative pulmonary complications independent of smoking status or sex.

We found that while there was no difference in disease-free survival between the PPCs and no-PPCs groups, PPCs had a negative effect on overall survival regardless of tumor stage. This finding indicates that PPC patients are continuously exposed to the risk of respiratory insufficiency after discharge, especially during the first year. We emphasize that patients who experienced PPCs require more careful and frequent short-term follow-up to improve overall survival.

In conclusion, preoperative serum fibrinogen levels of 400 mg/dL or greater, a surgical duration of 180 minutes or longer, and being male are the meaningful predictive factors for PPCs in surgical candidates. Measurements of preoperative serum fibrinogen levels will be helpful to predict PPCs. In addition, PPC patients are at risk of a shorter overall survival time regardless of tumor stage. An accurate prediction of PPCs can improve patient selection for appropriate treatment modalities and can help reduce overall medical costs related to treatments. The current findings indicate the need for further long-term follow-up studies in a prospective setting with a larger series of patients.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
The authors are grateful to Bo Ryong Hwang, RN, Eun-Ji Lee, RN, and Dong-Seok Han, RN, for their valuable contribution to collect the data in this article.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Wang J, Olak J, Ultmann RE, Ferguson MK. Assessment of pulmonary complications after lung resection Ann Thorac Surg 1999;67:1444-1447.[Abstract/Free Full Text]
  2. Hazelrigg SR, Landreneau RJ, Boley TM, et al. The effect of muscle-sparing versus standard posterolateral thoracotomy on pulmonary function, muscle strength, and postoperative pain J Thorac Carciovasc Surg 1991;101:394-400.[Abstract]
  3. Busch E, Verazin G, Antkowiak JG, Driscoll D, Takita H. Pulmonary complications in patients undergoing thoracotomy for lung resection Chest 1994;106:1930-1931.[Medline]
  4. Bolliger CT, Jordan P, Soler M, et al. Exercise capacity as a predictor of postoperative complications in lung resection candidates Am J Respir Crit Care Med 1995;151:1472-1480.[Abstract]
  5. Epstein SK, Faling LJ, Daly BD, Celli BR. Inability to perform bicycle ergometry predicts increased morbidity and mortality after lung resection Chest 1995;107:311-316.[Abstract/Free Full Text]
  6. Romano PS, Mark DH. Patient and hospital characteristics related to in-hospital mortality after lung cancer resection Chest 1992;101:1332-1337.[Abstract/Free Full Text]
  7. Wada H, Nakamura T, Nakamoto K, et al. Thirty-day operative mortality for thoracotomy in lung cancer J Thorac Cardiovasc Surg 1998;115:70-73.[Abstract/Free Full Text]
  8. Patel RL, Townsend ER, Fountain SW. Elective pneumonectomyfactors associated with morbidity and operative mortality. Ann Thorac Surg 1992;54:84-88.[Abstract]
  9. Nagasaki F, Flehinger BJ, Martini N. Complications of surgery in the treatment of carcinoma of the lung Chest 1982;82:25-29.[Abstract/Free Full Text]
  10. Harpole DH, Liptay MJ, DeCamp MM, et al. Prospective analysis of pneumonectomyrisk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg 1996;61:977-982.[Abstract/Free Full Text]
  11. Bagg LR. The 12-min walking distanceits use in the preoperative assessment of patients with bronchial carcinoma before lung resection. Respiration 1984;46:342-345.[Medline]
  12. Deslauriers J, Ginsberg RJ, Piantadosi S, et al. Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer Chest 1994;106(suppl):329S-330S.[Abstract/Free Full Text]
  13. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDSdefinitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-824.[Abstract]
  14. Lee HS, Lee JM, Kim MS, Kim HY, Hwangbo B, Zo JI. Low-dose steroid therapy at an early phase of postoperative acute respiratory distress syndrome Ann Thorac Surg 2005;79:405-410.[Abstract/Free Full Text]
  15. Yarnell JW, Baker IA, Sweetnam PM, et al. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease Circulation 1991;83:836-844.[Abstract/Free Full Text]
  16. Heinrich J, Balleisen L, Schulte H, Assmann G, Van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men Arterioscleros Thromb 1994;14:54-59.
  17. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation N Engl J Med 1999;340:448-454.[Free Full Text]
  18. Castell JV, Gomez-Lechon MJ, David M, et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes FEBS Lett 1989;242:237-239.[Medline]
  19. Ernst E, Resh KL. Fibrinogen as a cardiovascular risk factora meta-analysis and review of the literature. Ann Intern Med 1993;118:956-963.[Abstract/Free Full Text]
  20. Jacobson W, Park GR, Saich T, Holcroft J. Surfactant and adult respiratory distress syndrome. Br J Anaesth 70:522-6..
  21. Sack Jr GH, Levin J, Bell W. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasm Medicine 1977;56:1-37.[Medline]
  22. Gabazza EC, Taguchi O, Yamakami T, Machishi M, Ibata H, Suzuki S. Evaluating prethrombotic state in lung cancer using molecular markers Chest 1993;103:196-200.[Abstract/Free Full Text]
  23. Buccheri G, Ferrigno D, Ginardi C, Zuliani C. Haemostatic abnormalities in lung cancerprognostic implications. Eur J Cancer 1997;33:50-55.[Medline]
  24. vanWesch JW, Tjwa MK. Coagulation/fibrinolysis balance and lung cancer Haemostasis 1991;21:117-123.[Medline]
  25. Costantini V, Zacharski LR. Fibrin and cancer Thromb Hemost 1993;69:406-414.[Medline]
  26. Pavey SJ, Hawson G, Marsch NA. Alterations to the fibrinolytic enzyme system in patients with non small cell lung carcinoma Blood Coag Fibrinol 1999;10:261-267.[Medline]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
S.-W. Song, H.-S. Lee, J.-H. Kim, M. S. Kim, J. M. Lee, and J. I. Zo
Readmission to Intensive Care Unit After Initial Recovery From Major Thoracic Oncology Surgery
Ann. Thorac. Surg., December 1, 2007; 84(6): 1838 - 1846.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
S. R. Bapoje, J. F. Whitaker, T. Schulz, E. S. Chu, and R. K. Albert
Preoperative Evaluation of the Patient With Pulmonary Disease
Chest, November 1, 2007; 132(5): 1637 - 1645.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Hyun-Sung Lee
Moon Soo Kim
Jong Mog Lee
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Song, S.-W.
Right arrow Articles by Zo, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, S.-W.
Right arrow Articles by Zo, J. I.
Related Collections
Right arrow Lung - other

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS