Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2017, Vol. 11 Issue (2) : 239-246    https://doi.org/10.1007/s11684-017-0509-8
RESEARCH ARTICLE
Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgery for head and neck cancer
Yutao Liu1, Yaxia Di2, Shuai Fu3()
1. Department of Oral and Maxillofacial Surgery, Children’s Hospital, Chongqing Medical University, Chongqing 400014, China
2. Department of Research and Administration Services, Qujing No.1 Hospital, Qujing 655000, China
3. Department of Oral Surgery, Dental Hospital, Kunming Medical University, Kunming 650031, China
 Download: PDF(148 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Patients undergoing major oncological surgery for head and neck cancer (SHNC) have a particularly high risk of nosocomial infections. We aimed to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC. The study included 465 patients who underwent SHNC between June 2011 and June 2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were retrospectively evaluated. The incidence of VAP was 19.6% (n=95) in patients who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%), Enterobacteriaceae (32.1%), Pseudomonas (20.8%), and Haemophilus (16.9%) were the major bacterial species that caused VAP. The independent risk factors for VAP were advanced age, current smoking status, chronic obstructive pulmonary disease, and a higher simplified acute physiology score system II upon admission. Tracheostomy was an independent protective factor for VAP. The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days, respectively (P=0.006). Mortality among patients who did or did not develop VAP was 16.8% and 8.4%, respectively (P<0.001). The potential economic impact of VAP was high because of the significantly extended duration of ventilation. A predictive regression model was developed with a sensitivity of 95.3% and a specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation. Therefore, innovative preventive measures should be developed and applied in this high-risk population.

Keywords ventilator-associated pneumonia (VAP)      pneumonia      risk factors      surgery for head and neck cancer (SHNC)     
Corresponding Author(s): Shuai Fu   
Just Accepted Date: 16 March 2017   Online First Date: 11 May 2017    Issue Date: 01 June 2017
 Cite this article:   
Yutao Liu,Yaxia Di,Shuai Fu. Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgery for head and neck cancer[J]. Front. Med., 2017, 11(2): 239-246.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0509-8
https://academic.hep.com.cn/fmd/EN/Y2017/V11/I2/239
Patient characteristicsPatients with VAP (total=95),
n(%)
Patients without VAP (total=370),
n (%)
OR95% CIP
Male, n (%)63 (66.3)225 (60.8)1.260.77–2.110.324
Age, mean±SDb, year66.3±17.359.5±15.50.0002
BMIc, mean±SDb, kg/m225.7±4.624.9±4.10.098
Current smoker45 (47.4)126 (34.1)1.741.07–2.820.016
Medical comorbidity
ARDSd19 (20.0)65 (17.5)1.170.62–2.120.582
Cardiac insufficiency17 (17.9)50 (13.5)1.390.71–2.620.278
Immunosuppression27 (28.4)56 (15.1)2.221.25–3.880.003
Neurologic disease9 (9.5)35 (9.5)1.000.40–2.220.996
Diabetes mellitus14 (14.7)38 (10.3)1.510.71–3.010.218
COPDe30 (31.2)79 (21.3)1.701.00–2.860.035
Lung trauma7 (7.4)22 (5.9)1.250.43–3.170.609
Tumor site
Mouth/lip/submandibular gland43 (45.2)157 (42.4)0.521
Oropharynx25 (26.3)87 (23.5)
Larynx21 (22.1)84 (22.7)
Hypopharynx/esophagus6 (6.3)42 (11.4)
Mean GCSf on admission7.2±1.96.8±2.10.092
Mean SAPSg II on admission46.5±11.142.8±10.50.003
Serum albumin level (g/dl)4.61±0.664.40±0.580.003
Abnormal chest examination on admission9 (9.5)37 (10.0)0.940.38–2.080.878
Tracheostomy67 (70.5)302 (81.6)0.540.31–0.940.017
Prior antibiotic therapy82 (86.3)306 (82.7)1.320.67–2.740.398
Tumor size>2 cm63 (66.3)265 (71.6)0.780.47–1.310.311
Statin5 (5.3)20 (5.4)0.970.27–2.760.956
Tab.1  Univariate analysis of factors associated with VAPa in patients undergoing major oncological surgery for head and neck cancer
Characteristics during admissionPatients with VAP ,
n (%)
Patients without VAP,
n (%)
P
Median ICU length of stay, d8.06.50.006
Mean ventilation duration, d (mean±SD)15.1±5.213.0±4.1<0.0001
Mean length of surgery, h (mean±SD)4.8±1.34.6±0.90.081
Number of deaths in ICU16 (16.8)31 (8.4)<0.0001
Tab.2  Events in ICUa and crude outcomes in study patients
OrganismsEpisodes (total= 68)
n (%)
Staphylococcus20 (37.7)
Enterobacteriaceae17 (32.1)
Pseudomonas11 (20.8)
Hemophilus9 (16.9)
Pseudomonas4 (7.5)
Proteusspp.1 (1.9)
Klebsiellaspp.1 (1.9)
Serratiaspp.1 (1.9)
Other pathogens4 (7.5)
Tab.3  Bacterial spectrum for VAPa
VariablesOR95% CIP
Age1.151.04?1.280.01
Current smoker4.371.40?8.22<0.0001
COPDb2.351.30?4.770.0001
Mean SAPSc II on admission1.211.06?1.700.013
Tracheostomy0.720.55?0.980.005
Tab.4  Multivariate model of risk of VAPa in patients admitted to head and neck oncologic surgery
Fig.1  Receiver operating characteristic (ROC) curve drawn for the model built using coefficients. Development subsample, c-statistic for the area under the ROC curve (AUC) = 0.8914 (95%CI, 0.84–0.94).
1 Bigham MT, Amato R, Bondurrant P, Fridriksson J, Krawczeski CD, Raake J, Ryckman S, Schwartz S, Shaw J, Wells D, Brilli RJ. Ventilator-associated pneumonia in the pediatric intensive care unit: characterizing the problem and implementing a sustainable solution. J Pediatr 2009; 154(4): 582–587.e2
https://doi.org/10.1016/j.jpeds.2008.10.019 pmid: 19054530
2 Shorr AF, Tabak YP, Gupta V, Johannes RS, Liu LZ, Kollef MH. Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia. Crit Care 2006; 10(3): R97
https://doi.org/10.1186/cc4934 pmid: 16808853
3 Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH; VAP Outcomes Scientific Advisory Group. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002; 122(6): 2115–2121
https://doi.org/10.1378/chest.122.6.2115 pmid: 12475855
4 Vallés J, Pobo A, García-Esquirol O, Mariscal D, Real J, Fernández R. Excess ICU mortality attributable to ventilator-associated pneumonia: the role of early vs. late onset. Intensive Care Med 2007; 33(8): 1363–1368
https://doi.org/10.1007/s00134-007-0721-0 pmid: 17558495
5 Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005; 33(10): 2184–2193
https://doi.org/10.1097/01.CCM.0000181731.53912.D9 pmid: 16215368
6 Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med 1999; 159(4): 1249–1256
https://doi.org/10.1164/ajrccm.159.4.9807050 pmid: 10194173
7 Petrar S, Bartlett C, Hart RD, MacDougall P. Pulmonary complications after major head and neck surgery: a retrospective cohort study. Laryngoscope 2012; 122(5): 1057–1061
https://doi.org/10.1002/lary.23228 pmid: 22447296
8 Ong SK, Morton RP, Kolbe J, Whitlock RM, McIvor NP. Pulmonary complications following major head and neck surgery with tracheostomy: a prospective, randomized, controlled trial of prophylactic antibiotics. Arch Otolaryngol Head Neck Surg 2004; 130(9): 1084–1087
https://doi.org/10.1001/archotol.130.9.1084 pmid: 15381595
9 McCulloch TM, Jensen NF, Girod DA, Tsue TT, Weymuller EA Jr. Risk factors for pulmonary complications in the postoperative head and neck surgery patient. Head Neck 1997; 19(5): 372–377
https://doi.org/10.1002/(SICI)1097-0347(199708)19:5<372::AID-HED2>3.0.CO;2-X pmid: 9243263
10 Kakavas S, Mongardon N, Cariou A, Gulati A, Xanthos T. Early-onset pneumonia after out-of-hospital cardiac arrest. J Infect 2015; 70(6): 553–562
https://doi.org/10.1016/j.jinf.2015.01.012 pmid: 25644317
11 Li S, Zhang Y, Li S, Wang X, Zhang R, Lu Z, Yan J. Risk factors associated with prolonged mechanical ventilation after corrective surgery for tetralogy of Fallot. Congenit Heart Dis 2015; 10(3): 254–262
https://doi.org/10.1111/chd.12205 pmid: 25059746
12 Inchai J, Pothirat C, Liwsrisakun C, Deesomchok A, Kositsakulchai W, Chalermpanchai N. Ventilator-associated pneumonia: epidemiology and prognostic indicators of 30-day mortality. Jpn J Infect Dis 2015; 68(3): 181–186
https://doi.org/10.7883/yoken.JJID.2014.282 pmid: 25672347
13 Gianakis A, McNett M, Belle J, Moran C, Grimm D. Risk factors for ventilator-associated pneumonia: among trauma patients with and without brain injury. J Trauma Nurs 2015; 22(3): 125–131
https://doi.org/10.1097/JTN.0000000000000121 pmid: 25961478
14 Berlet T, Etter R, Fehr T, Berger D, Sendi P, Merz TM. Sonographic patterns of lung consolidation in mechanically ventilated patients with and without ventilator-associated pneumonia: a prospective cohort study. J Crit Care 2015; 30(2): 327–333
https://doi.org/10.1016/j.jcrc.2014.11.021 pmid: 25499414
15 Semenov YR, Starmer HM, Gourin CG. The effect of pneumonia on short-term outcomes and cost of care after head and neck cancer surgery. Laryngoscope 2012; 122(9): 1994–2004
https://doi.org/10.1002/lary.23446 pmid: 22777881
16 Goutier JM, Holzmueller CG, Edwards KC, Klompas M, Speck K, Berenholtz SM. Strategies to enhance adoption of ventilator-associated pneumonia prevention interventions: a systematic literature review. Infect Control Hosp Epidemiol 2014; 35(8): 998–1005
https://doi.org/10.1086/677152 pmid: 25026616
17 Maselli DJ, Restrepo MI. Strategies in the prevention of ventilator-associated pneumonia. Ther Adv Respir Dis 2011; 5(2): 131–141
https://doi.org/10.1177/1753465810395655 pmid: 21300737
18 Klompas M, Kleinman K, Murphy MV, Program CPE. Descriptive epidemiology and attributable morbidity of ventilator-associated events. Infect Control Hosp Epidemiol 2014; 35(5): 502–510
https://doi.org/10.1086/675834 pmid: 24709718
19 Bercault N, Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med 2001; 29(12): 2303–2309
https://doi.org/10.1097/00003246-200112000-00012 pmid: 11801831
20 Warren DK, Shukla SJ, Olsen MA, Kollef MH, Hollenbeak CS, Cox MJ, Cohen MM, Fraser VJ. Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med 2003; 31(5): 1312–1317
https://doi.org/10.1097/01.CCM.0000063087.93157.06 pmid: 12771596
21 Bird D, Zambuto A, O’Donnell C, Silva J, Korn C, Burke R, Burke P, Agarwal S. Adherence to ventilator-associated pneumonia bundle and incidence of ventilator-associated pneumonia in the surgical intensive care unit. Arch Surg 2010; 145(5): 465–470
https://doi.org/10.1001/archsurg.2010.69 pmid: 20479345
22 Bronchard R, Albaladejo P, Brezac G, Geffroy A, Seince PF, Morris W, Branger C, Marty J. Early onset pneumonia: risk factors and consequences in head trauma patients. Anesthesiology 2004; 100(2): 234–239
https://doi.org/10.1097/00000542-200402000-00009 pmid: 14739794
23 Lepelletier D, Roquilly A, Demeure dit latte D, Mahe PJ, Loutrel O, Champin P, Corvec S, Naux E, Pinaud M, Lejus C, Asehnoune K. Retrospective analysis of the risk factors and pathogens associated with early-onset ventilator-associated pneumonia in surgical-ICU head-trauma patients. J Neurosurg Anesthesiol 2010; 22(1): 32–37
https://doi.org/10.1097/ANA.0b013e3181bdf52f pmid: 20027012
24 American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171(4): 388–416
https://doi.org/10.1164/rccm.200405-644ST pmid: 15699079
25 Weksler ME, Hütteroth TH. Impaired lymphocyte function in aged humans. J Clin Invest 1974; 53(1): 99–104
https://doi.org/10.1172/JCI107565 pmid: 4855547
26 Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest 2001; 120(3): 705–710
https://doi.org/10.1378/chest.120.3.705 pmid: 11555496
27 Barrera R, Shi W, Amar D, Thaler HT, Gabovich N, Bains MS, White DA. Smoking and timing of cessation: impact on pulmonary complications after thoracotomy. Chest 2005; 127(6): 1977–1983
https://doi.org/10.1378/chest.127.6.1977 pmid: 15947310
28 Wong J, Lam DP, Abrishami A, Chan MT, Chung F. Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis. Can J Anaesth 2012; 59(3): 268–279
https://doi.org/10.1007/s12630-011-9652-x pmid: 22187226
29 Kotani N, Kushikata T, Hashimoto H, Sessler DI, Muraoka M, Matsuki A. Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period. Anesthesiology 2001; 94(6): 999–1006
https://doi.org/10.1097/00000542-200106000-00013 pmid: 11465626
30 Makris D, Desrousseaux B, Zakynthinos E, Durocher A, Nseir S. The impact of COPD on ICU mortality in patients with ventilator-associated pneumonia. Respir Med 2011; 105(7): 1022–1029
https://doi.org/10.1016/j.rmed.2011.03.001 pmid: 21435855
31 Nseir S, Di Pompeo C, Soubrier S, Cavestri B, Jozefowicz E, Saulnier F, Durocher A. Impact of ventilator-associated pneumonia on outcome in patients with COPD. Chest 2005; 128(3): 1650–1656
https://doi.org/10.1378/chest.128.3.1650 pmid: 16162771
32 Rinaudo M, Ferrer M, Terraneo S, De Rosa F, Peralta R, Fernández-Barat L, Li Bassi G, Torres A. Impact of COPD in the outcome of ICU-acquired pneumonia with and without previous intubation. Chest 2015; 147(6): 1530–1538
https://doi.org/10.1378/chest.14-2005 pmid: 25612147
33 Di Pasquale M, Esperatti M, Crisafulli E, Ferrer M, Bassi GL, Rinaudo M, Escorsell A, Fernandez J, Mas A, Blasi F, Torres A. Impact of chronic liver disease in intensive care unit acquired pneumonia: a prospective study. Intensive Care Med 2013; 39(10): 1776–1784
https://doi.org/10.1007/s00134-013-3025-6 pmid: 23907496
34 Ranzani OT, Ferrer M, Esperatti M, Giunta V, Bassi GL, Carvalho CR, Torres A. Association between systemic corticosteroids and outcomes of intensive care unit-acquired pneumonia. Crit Care Med 2012; 40(9): 2552–2561
https://doi.org/10.1097/CCM.0b013e318259203d pmid: 22732293
35 Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187(4): 347–365
https://doi.org/10.1164/rccm.201204-0596PP pmid: 22878278
36 Kanna B, Ayman HA, Soni A. Early tracheostomy in intensive care trauma patient improves resource utilization: a cohort study and literature review. Crit Care 2005; 9(4): 414–416
https://doi.org/10.1186/cc3043 pmid: 16137393
37 Schneider GT, Christensen N, Doerr TD. Early tracheotomy in elderly patients results in less ventilator-associated pneumonia. Otolaryngol Head Neck Surg 2009; 140(2): 250–255
https://doi.org/10.1016/j.otohns.2008.11.006 pmid: 19201298
38 Terragni PP, Antonelli M, Fumagalli R, Faggiano C, Berardino M, Pallavicini FB, Miletto A, Mangione S, Sinardi AU, Pastorelli M, Vivaldi N, Pasetto A, Della Rocca G, Urbino R, Filippini C, Pagano E, Evangelista A, Ciccone G, Mascia L, Ranieri VM. Early vs. late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial. JAMA 2010; 303(15): 1483–1489
https://doi.org/10.1001/jama.2010.447 pmid: 20407057
39 Arabi Y, Haddad S, Shirawi N, Al Shimemeri A. Early tracheostomy in intensive care trauma patients improves resource utilization: a cohort study and literature review. Crit Care 2004; 8(5): R347–R352
https://doi.org/10.1186/cc2924 pmid: 15469579
40 Devarajan J, Vydyanathan A, Xu M, Murthy SM, McCurry KR, Sessler DI, Sabik J, Bashour CA. Early tracheostomy is associated with improved outcomes in patients who require prolonged mechanical ventilation after cardiac surgery. J Am Coll Surg 2012; 214(6): 1008–16.e4
https://doi.org/10.1016/j.jamcollsurg.2012.03.005 pmid: 22541987
41 Rumbak MJ, Newton M, Truncale T, Schwartz SW, Adams JW, Hazard PB. A prospective, randomized, study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed tracheotomy) in critically ill medical patients. Crit Care Med 2004; 32(8): 1689–1694
https://doi.org/10.1097/01.CCM.0000134835.05161.B6 pmid: 15286545
42 Blot F, Similowski T, Trouillet JL, Chardon P, Korach JM, Costa MA, Journois D, Thiéry G, Fartoukh M, Pipien I, Bruder N, Orlikowski D, Tankere F, Durand-Zaleski I, Auboyer C, Nitenberg G, Holzapfel L, Tenaillon A, Chastre J, Laplanche A. Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients. Intensive Care Med 2008; 34(10): 1779–1787
https://doi.org/10.1007/s00134-008-1195-4 pmid: 18592210
43 Nieszkowska A, Combes A, Luyt CE, Ksibi H, Trouillet JL, Gibert C, Chastre J. Impact of tracheotomy on sedative administration, sedation level, and comfort of mechanically ventilated intensive care unit patients. Crit Care Med 2005; 33(11): 2527–2533
https://doi.org/10.1097/01.CCM.0000186898.58709.AA pmid: 16276177
44 Kollef MH, Zilberberg MD, Shorr AF, Vo L, Schein J, Micek ST, Kim M. Epidemiology, microbiology and outcomes of healthcare-associated and community-acquired bacteremia: a multicenter cohort study. J Infect 2011; 62(2): 130–135
https://doi.org/10.1016/j.jinf.2010.12.009 pmid: 21195110
45 Moore CL, Hingwe A, Donabedian SM, Perri MB, Davis SL, Haque NZ, Reyes K, Vager D, Zervos MJ. Comparative evaluation of epidemiology and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infections causing community- and healthcare-associated infections. Int J Antimicrob Agents 2009; 34(2): 148–155
https://doi.org/10.1016/j.ijantimicag.2009.03.004 pmid: 19394801
46 Fujita T, Sakurai K. Multivariate analysis of risk factors for postoperative pneumonia. Am J Surg 1995; 169(3): 304–307
https://doi.org/10.1016/S0002-9610(99)80163-9 pmid: 7879831
47 Liu C, Du Z, Zhou Q, Hu B, Li Z, Yu L, Xu T, Fan X, Yang J, Li J. Microscopic examination of intracellular organisms in bronchoalveolar lavage fluid for the diagnosis of ventilator-associated pneumonia: a prospective multi-center study. Chin Med J (Engl) 2014; 127(10): 1808–1813
pmid: 24824236
[1] Rongmeng Jiang, Bing Han, Chang Dou, Fei Zhou, Bin Cao, Xingwang Li. Analysis of antibiotic usage for viral community-acquired pneumonia in adults[J]. Front. Med., 2021, 15(1): 139-143.
[2] Xiaowei Zhu, Houfeng Zheng. Factors influencing peak bone mass gain[J]. Front. Med., 2021, 15(1): 53-69.
[3] Fanghua Gong, Yong Xiong, Jian Xiao, Li Lin, Xiaodong Liu, Dezhong Wang, Xiaokun Li. China’s local governments are combating COVID-19 with unprecedented responses ---- from a Wenzhou governance perspective[J]. Front. Med., 2020, 14(2): 220-224.
[4] Sasa Nie, Zhe Feng, Lihua Xia, Jiuxu Bai, Fenglin Xiao, Jian Liu, Li Tang, Xiangmei Chen. Risk factors of prognosis after acute kidney injury in hospitalized patients[J]. Front. Med., 2017, 11(3): 393-402.
[5] Jananni Muthu,Sivaramakrishnan Muthanandam,Jaideep Mahendra. Mouth the mirror of lungs: where does the connection lie?[J]. Front. Med., 2016, 10(4): 405-409.
[6] Alexandra Urman,H. Dean Hosgood. Curbing the burden of lung cancer[J]. Front. Med., 2016, 10(2): 228-232.
[7] Zhiming Zhu, Peijian Wang, Shuangtao Ma. Metabolic hypertension: concept and practice[J]. Front Med, 2013, 7(2): 201-206.
[8] Jin Gao, Ben Panizza, Newell W. Johnson, Scott Coman, Alan R. Clough. Basic consideration of research strategies for head and neck cancer[J]. Front Med, 2012, 6(4): 339-353.
[9] Marie-Germaine Bousser. Stroke prevention: an update[J]. Front Med, 2012, 6(1): 22-34.
[10] Jing LI, Ying FU, Ji-Yao WANG, Chuan-Tao TU, Xi-Zhong SHEN, Lei LI, Wei JIANG. Early diagnosis and therapeutic choice of Klebsiella pneumoniae liver abscess[J]. Front Med Chin, 2010, 4(3): 308-316.
[11] Jun-Jie XIAO MD, Yi-Han CHEN MD, PhD, . Prevalence of cardiovascular diseases in China[J]. Front. Med., 2010, 4(1): 16-20.
[12] Qiong DAI MD, Bei LIU MD, Yukai DU MM, . Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive use[J]. Front. Med., 2009, 3(4): 452-458.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed