Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 719-723

Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma

1 2nd Department of Surgery, Aretaieio University Hospital, National and Kapodistrian University of Athens, Athens, Greece
2 Department of Pathology, Aretaieio University Hospital, National and Kapodistrian University of Athens, Athens, Greece

Date of Web Publication24-Sep-2018

Correspondence Address:
Panagis M Lykoudis
2nd Department of Surgery, Aretaieio University Hospital, 75, Vas. Sofias Ave., Athens, 11528
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.187346

Rights and Permissions
 > Abstract 

Context: Survivin is an antiapoptotic protein with a role in tumorigenesis and suggested prognostic value in several proliferative diseases.
Aims: This study aimed to examine the role of survivin as a prognostic marker in pancreatic adenocarcinoma (PDAC).
Settings and Design: Fifty-one specimens of PDAC were assessed for survivin expression by immunohistochemistry.
Subjects and Methods: Overall survival and 1-, 3-, and 5-year survival were retrieved retrospectively.
Statistical Analysis Used: Bivariate analysis was conducted using Chi-square and Mann–Whitney U tests, while survival analysis was conducted using Kaplan–Meier statistics.
Results: Of the 51 assessed cases, 49% were positive for survivin. Survivin expression was significantly correlated 1-year survival and overall survival, particularly in bcl-2 positive cases.
Conclusions: Survivin may be implicated in the bcl-2 and p53 pathways and therefore in the biology of PDAC. Its potential use as a survival predictor and therapeutic target represent a promising field.

Keywords: Apoptosis, pancreatic adenocarcinoma, survival, survivin

How to cite this article:
Contis J, Lykoudis PM, Goula K, Karandrea D, Kondi-Pafiti A. Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma. J Can Res Ther 2018;14, Suppl S3:719-23

How to cite this URL:
Contis J, Lykoudis PM, Goula K, Karandrea D, Kondi-Pafiti A. Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma. J Can Res Ther [serial online] 2018 [cited 2022 May 28];14, Suppl S3:719-23. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/719/187346

 > Introduction Top

Pancreatic adenocarcinoma (PDAC) remains the fourth cause of death due to malignancies in the USA[1] with an overall 5-year survival of <5%.[2] Despite the progress in our understanding of PDAC biology, as well as advances in diagnosis and treatment, survival rates seem to decrease, unlike other malignancies.[3] The diagnosis of PDAC in later stages and lack of precise stratification of patients for successful treatment tailoring are considered the main causes for these outcomes.[4] A number of molecules have been proposed in literature as predictors for survival, appearing thus as candidates for inclusion in prognostic models and for molecular targeted therapies.

Survivin is a member of the inhibitors of the apoptosis family, involved in cell division regulation and inhibition of apoptosis. Overexpression of survivin has been found in many human malignancies including lymphoma[5],[6] and nonsmall cell lung cancer,[7] usually accompanying more aggressive forms followed by worse outcomes.[8] Research on targeting survivin in an effort to inhibit its proliferative action in malignancies has yielded encouraging results concerning different types of cancer.[9],[10]

This study aims to reassess the potential prognostic role of survivin expression in PDAC as well as to examine whether established prognostic markers are confounding factors in the correlation between survivin expression and overall survival.

 > Subjects and Methods Top

The archives of the Pathology Department of a single tertiary center were searched for specimens regarding PDAC during a 5-year period (2003–2007). Fifty-one consecutive cases were identified, and relevant paraffin-embedded archived tissue and histopathology slides were retrieved. Sections from the archived paraffin-embedded tumor tissues were obtained and examined by Ventana automatic immunostain method, using antihuman bcl-2 protein (DAKO M0887, clone 124), p53 antibody (DAKO, M7001, DO-7), EGFR (Zymed Lab Inc., San Francisco, CA, USA), and survivin (A-Diagnostics Intern, San Antonio, TX, USA) according to manufacturers' instructions with appropriate positive and negative controls. The immunoreaction was evaluated semiquantitatively, depending on the percentage of positively stained cells to the total number of cells examined (at least 100 cells/case). The score was considered negative (-) where the percentage of positively stained cells was <10% of total cells examined, and positive (+) where >10% of cells were stained. Positive immunoreaction was observed at the nuclei (p53), the cytoplasm (bcl-2 and survivin), and at the cellular membrane and the cytoplasm (EGFR). Data regarding patient's gender and age, as well as tumor grading, were obtained from the relevant histopathology reports. The archives of the oncology department were accessed to document data regarding survival. None of the included patients was lost during follow-up, thus patients who were still alive at the time data were collected, had completed a 5-year follow-up. Overall survival was calculated from the time of surgical operation, and survival in 1, 3, and 5 years were calculated accordingly.

Chi-square and Mann–Whitney U tests were used for univariate analyses, and Kaplan–Meier analysis was additionally applied for correlation of survival with various independent variables. For the latter analysis, Breslow test was used to test for statistical significance because most deaths are expected early in the postoperative course, given the short survival of pancreatic cancer patients, and thus proportional hazards assumption is expected to be not true.[11],[12]

All patients had consented for tissue preservation and research investigations; the study confirmed with The Code of Ethics of the World Medical Association and the approval of hospital's Ethical Committee.

 > Results Top

Of a total of 51 patients, 62.7% were male (n = 32) and 37.3% were female (n = 19). Median age was 67 years (ranging between 35 and 78 years, 95% confidence interval [CI]: 63–69 years) and median overall survival was 12 months (ranging between 5 and 106 months, 95% CI: 7–17). Twelve patients had a Grade I tumor (23.5%), 23 patients had a Grade II tumor (45.1%), and 16 patients had a Grade III tumor (31.4%). The expression ratio for each protein is presented in [Table 1]. Eleven specimens were negative for all proteins (19%), seven specimens demonstrated expression of only one marker (12.1%), two markers were expressed in 16 specimens (27.6%), 15 specimens were positive for 3 factors (25.9%), and finally all four proteins were expressed in nine specimens (15.5%). One-year, 3-year, and 5-year survivals were 51%, 11.8%, and 5.9%, respectively.
Table 1: Expression ratios of studied proteins

Click here to view

Survivin expression was found to have statistically significant correlation with tumor grade (P = 0.025) and with p53 expression (P = 0.016), as well as with 1-year survival (P = 0.008) and overall survival (Breslow [generalized Wilcoxon] P = 0.035). Correlations of survivin expression with age, gender, EGFR expression, and bcl-2 expression were not statistically significant nor were those with 3- and 5-year survival. As far as correlations between survival outcomes and the rest of the independent variables (age, gender, grade, p53, bcl-2, and EGFR) are concerned, the only detected statistically significant correlation was the one between bcl-2 and five-year survival.

A Kaplan–Meier curve was created to demonstrate the correlation between survivin expression and overall survival (Breslow P = 0.035) [Figure 1]. According to the same method and using each of the other independent variables as a stratification variable, bcl-2 expression appeared as a confounding factor to the correlation between overall survival and survivin expression. The latter correlation remained statistically significant only in bcl-2 positive cases [Figure 2] but was insignificant in bcl-2 negative cases [Figure 3].
Figure 1: Kaplan–Meier analysis of overall survival according to survivin expression

Click here to view
Figure 2: Kaplan–Meier analysis of overall survival according to survivin expression on bcl-2 positive specimens demonstrating nonsignificant correlation

Click here to view
Figure 3: Kaplan–Meier analysis of overall survival according to survivin expression on bcl-2 negative specimens demonstrating nonsignificant correlation

Click here to view

 > Discussion Top

Since 1997, when Ambrosini et al. first reported the involvement of survivin in PDAC development and biological behavior,[6] numerous research groups studied the role of this molecule in pancreatic cancer biology. Initially, it was demonstrated that survivin plays a significant role in apoptosis of PDAC cells.[13] Several proliferative mechanisms, including Protein Kinases C[14] and the MEK-ERK pathway,[15] have been shown to mediate survivin's antiapoptotic action. Bhanot et al. also demonstrated that survivin expression increases as precancerous lesions evolve into phenotypically unambiguous infiltrative carcinoma.[16] Survivin was also tested as a biomarker to help differentiate between malignant and benign disease in fine needle aspiration specimens, unfortunately without success though.[17] Moreover, a number of studies have suggested that survivin may potentiate resistance of PDAC cells to certain chemotherapeutic agents, and consequently suppression of survivin's expression may restore/augment response to these agents.[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29] Based on these findings, several groups have tried to downregulate survivin's function through immunological approaches[30],[31] or genomic approaches such as antisense nucleotides, gene silencing, and translation inhibition.[32],[33],[34],[35]

Survivin has been studied as a prognostic factor in PDAC, but although some groups have reported results which support such a role for survivin,[18],[36],[37],[38],[39] other groups did not detect the aforementioned correlation.[13],[40],[41] The only meta-analysis that has addressed this inconsistency detects a prognostic role for survivin; however, the authors of this paper admit certain weaknesses, involving mainly heterogeneity of outcome assessment among included studies that must be considered before adopting its conclusions.[42] Besides, given that survivin expression has been correlated with the expression of other established prognostic factors such as bcl-2,[43] EGFR,[44],[45] and p53,[13],[46] the reported relation between survivin expression and clinical outcomes may be secondary to the aforementioned correlations and it is thus unclear whether survivin is an independent prognostic factor.

In the present study, 54.9% of tumors were survivin positive while the reported ratio of survivin-positive PDACs varies between 44.8 and 93.9% in literature.[37],[41] This study reports a statistically significant correlation between survivin expression and overall survival, reproducing thus the findings of previous research groups.[36],[37],[38],[39] In the studied sample, only bcl-2 expression qualified as a potential confounding factor and was investigated accordingly. On stratification of studied subjects according to bcl-2 expression, survivin maintained its prognostic role only in bcl-2 positive specimens. It can be argued thus that survivin is an independent prognostic factor in bcl-2 positive PDACs, with survivin-negative tumors associated with a prolonged overall survival, while in bcl-2 negative PDACs, this correlation is lost. It is characteristically reported in literature that simultaneous silencing of bcl-2 and survivin may augment cancer cell apoptosis.[34] It can also be suggested that since survivin and p53 expressions show a statistically significant correlation, they may share partially common or at least linked molecular pathways. The latter correlation has also been reported previously in literature.[13]

The above findings suggest a potential significant functional role of survivin in the biology of PDAC, linked with p53 and bcl-2 functions, and they also define a subgroup of patients, those with bcl-2 positive tumors, in which survivin expression is associated with worse survival and thus could be a used as a treatment target. However, this is a small cohort study, and relevant findings and conclusions should be investigated in larger series in order to establish solid deductions.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Hidalgo M. Pancreatic cancer. N Engl J Med 2010;362:1605-17.  Back to cited text no. 1
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363:1049-57.  Back to cited text no. 2
Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2012. Ann Oncol 2012;23:1044-52.  Back to cited text no. 3
Klein AP. Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer 2013;13:66-74.  Back to cited text no. 4
Schlette EJ, Medeiros LJ, Goy A, Lai R, Rassidakis GZ. Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma. J Clin Oncol 2004;22:1682-8.  Back to cited text no. 5
Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917-21.  Back to cited text no. 6
Monzó M, Rosell R, Felip E, Astudillo J, Sánchez JJ, Maestre J, et al. A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol 1999;17:2100-4.  Back to cited text no. 7
Kuttler F, Valnet-Rabier MB, Angonin R, Ferrand C, Deconinck E, Mougin C, et al. Relationship between expression of genes involved in cell cycle control and apoptosis in diffuse large B cell lymphoma: A preferential survivin-cyclin B link. Leukemia 2002;16:726-35.  Back to cited text no. 8
Yang L, Cao Z, Yan H, Wood WC. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy. Cancer Res 2003;63:6815-24.  Back to cited text no. 9
Vogler M, Giagkousiklidis S, Genze F, Gschwend JE, Debatin KM, Fulda S. Inhibition of clonogenic tumor growth: A novel function of Smac contributing to its antitumor activity. Oncogene 2005;24:7190-202.  Back to cited text no. 10
Machin D, Cheung YB, Parmar M. Survival Analysis: A Practical Approach. 2nd ed. West Sussex, England: Wiley; 2006.  Back to cited text no. 11
Martinez RL, Naranjo JD. A pretest for choosing between logrank and wilcoxon tests in the two-sample problem. Metron 2010;68:111-25.  Back to cited text no. 12
Sarela AI, Verbeke CS, Ramsdale J, Davies CL, Markham AF, Guillou PJ. Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. Br J Cancer 2002;86:886-92.  Back to cited text no. 13
Trauzold A, Schmiedel S, Sipos B, Wermann H, Westphal S, Röder C, et al. PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells. Oncogene 2003;22:8939-47.  Back to cited text no. 14
Yip-Schneider MT, Schmidt CM. MEK inhibition of pancreatic carcinoma cells by U0126 and its effect in combination with sulindac. Pancreas 2003;27:337-44.  Back to cited text no. 15
Bhanot U, Heydrich R, Möller P, Hasel C. Survivin expression in pancreatic intraepithelial neoplasia (PanIN): Steady increase along the developmental stages of pancreatic ductal adenocarcinoma. Am J Surg Pathol 2006;30:754-9.  Back to cited text no. 16
Jhala N, Jhala D, Vickers SM, Eltoum I, Batra SK, Manne U, et al. Biomarkers in diagnosis of pancreatic carcinoma in fine-needle aspirates. Am J Clin Pathol 2006;126:572-9.  Back to cited text no. 17
Xie H, Jiang W, Xiao SY, Liu X. High expression of survivin is prognostic of shorter survival but not predictive of adjuvant gemcitabine benefit in patients with resected pancreatic adenocarcinoma. J Histochem Cytochem 2013;61:148-55.  Back to cited text no. 18
Rathos MJ, Joshi K, Khanwalkar H, Manohar SM, Joshi KS. Molecular evidence for increased antitumor activity of gemcitabine in combination with a cyclin-dependent kinase inhibitor, P276-00 in pancreatic cancers. J Transl Med 2012;10:161.  Back to cited text no. 19
Urick ME, Chung EJ, Shield WP 3rd, Gerber N, White A, Sowers A, et al. Enhancement of 5-fluorouracil-induced in vitro and in vivo radiosensitization with MEK inhibition. Clin Cancer Res 2011;17:5038-47.  Back to cited text no. 20
Taeger J, Moser C, Hellerbrand C, Mycielska ME, Glockzin G, Schlitt HJ, et al. Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer. Mol Cancer Ther 2011;10:2157-67.  Back to cited text no. 21
Du Z, Qin R, Wei C, Wang M, Shi C, Tian R, et al. Pancreatic cancer cells resistant to chemoradiotherapy rich in stem-cell-like tumor cells. Dig Dis Sci 2011;56:741-50.  Back to cited text no. 22
Sung B, Park B, Yadav VR, Aggarwal BB. Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem 2010;285:11498-507.  Back to cited text no. 23
Huanwen W, Zhiyong L, Xiaohua S, Xinyu R, Kai W, Tonghua L. Intrinsic chemoresistance to gemcitabine is associated with constitutive and laminin-induced phosphorylation of FAK in pancreatic cancer cell lines. Mol Cancer 2009;8:125.  Back to cited text no. 24
Lang SA, Schachtschneider P, Moser C, Mori A, Hackl C, Gaumann A, et al. Dual targeting of Raf and VEGF receptor 2 reduces growth and metastasis of pancreatic cancer through direct effects on tumor cells, endothelial cells, and pericytes. Mol Cancer Ther 2008;7:3509-18.  Back to cited text no. 25
Lopes RB, Gangeswaran R, McNeish IA, Wang Y, Lemoine NR. Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy. Int J Cancer 2007;120:2344-52.  Back to cited text no. 26
Plastaras JP, Cengel KA. Combination therapy with gemcitabine and 5-Fluorouracil: Unblocking the pathways to survivin? Cancer Biol Ther 2006;5:1566-8.  Back to cited text no. 27
El-Rayes BF, Ali S, Ali IF, Philip PA, Abbruzzese J, Sarkar FH. Potentiation of the effect of erlotinib by genistein in pancreatic cancer: The role of Akt and nuclear factor-kappaB. Cancer Res 2006;66:10553-9.  Back to cited text no. 28
Banerjee S, Kong D, Azmi AS, Wang Z, Ahmad A, Sethi S, et al. Restoring sensitivity to oxaliplatin by a novel approach in gemcitabine-resistant pancreatic cancer cells in vitro and in vivo. Int J Cancer 2011;128:1240-50.  Back to cited text no. 29
Kameshima H, Tsuruma T, Kutomi G, Shima H, Iwayama Y, Kimura Y, et al. Immunotherapeutic benefit of a-interferon (IFNalpha) in survivin2B-derived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci 2013;104:124-9.  Back to cited text no. 30
Ishizaki H, Manuel ER, Song GY, Srivastava T, Sun S, Diamond DJ, et al. Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model. Cancer Immunol Immunother 2011;60:99-109.  Back to cited text no. 31
Jiang C, Tan T, Yi XP, Shen H, Li YX. Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo. Mol Med Rep 2011;4:667-74.  Back to cited text no. 32
Carrasco RA, Stamm NB, Marcusson E, Sandusky G, Iversen P, Patel BK. Antisense inhibition of survivin expression as a cancer therapeutic. Mol Cancer Ther 2011;10:221-32.  Back to cited text no. 33
Rückert F, Samm N, Lehner AK, Saeger HD, Grützmann R, Pilarsky C. Simultaneous gene silencing of Bcl-2, XIAP and survivin re-sensitizes pancreatic cancer cells towards apoptosis. BMC Cancer 2010;10:379.  Back to cited text no. 34
Lin L, Hutzen B, Li PK, Ball S, Zuo M, DeAngelis S, et al. A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growth-suppressive activity in human cancer cells. Neoplasia 2010;12:39-50.  Back to cited text no. 35
Ansari D, Rosendahl A, Elebro J, Andersson R. Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer. Br J Surg 2011;98:1041-55.  Back to cited text no. 36
Tonini G, Vincenzi B, Santini D, Scarpa S, Vasaturo T, Malacrino C, et al. Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients. Br J Cancer 2005;92:2225-32.  Back to cited text no. 37
Kami K, Doi R, Koizumi M, Toyoda E, Mori T, Ito D, et al. Survivin expression is a prognostic marker in pancreatic cancer patients. Surgery 2004;136:443-8.  Back to cited text no. 38
Ekeblad S, Lejonklou MH, Stålberg P, Skogseid B. Prognostic relevance of survivin in pancreatic endocrine tumors. World J Surg 2012;36:1411-8.  Back to cited text no. 39
Sagol O, Yavuzsen T, Oztop I, Ulukus C, Ylmaz U, Alakavuklar M, et al. The effect of apoptotic activity, survivin, Ki-67, and P-glycoprotein expression on prognosis in pancreatic carcinoma. Pancreas 2005;30:343-8.  Back to cited text no. 40
Lee MA, Park GS, Lee HJ, Jung JH, Kang JH, Hong YS, et al. Survivin expression and its clinical significance in pancreatic cancer. BMC Cancer 2005;5:127.  Back to cited text no. 41
Jamieson NB, Carter CR, McKay CJ, Oien KA. Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis. Clin Cancer Res 2011;17:3316-31.  Back to cited text no. 42
Qiao JG, Zhang YQ, Yin YC, Tan Z. Expression of survivin in pancreatic cancer and its correlation to expression of Bcl-2. World J Gastroenterol 2004;10:2759-61.  Back to cited text no. 43
Na YS, Yang SJ, Kim SM, Jung KA, Moon JH, Shin JS, et al. YM155 induces EGFR suppression in pancreatic cancer cells. PLoS One 2012;7:e38625.  Back to cited text no. 44
Wang H, Gambosova K, Cooper ZA, Holloway MP, Kassai A, Izquierdo D, et al. EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic ß-cells. BMC Mol Biol 2010;11:66.  Back to cited text no. 45
Tsuji N, Furuse K, Asanuma K, Furuya M, Kondoh K, Kamagata C, et al. Mutations of the p53 gene and loss of heterozygosity at chromosome 17p13.1 are associated with increased survivin expression in breast cancer. Breast Cancer Res Treat 2004;87:23-31.  Back to cited text no. 46


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

This article has been cited by
1 Application of Proteomics in Pancreatic Ductal Adenocarcinoma Biomarker Investigations: A Review
Christina Jane Vellan, Jaime Jacqueline Jayapalan, Boon-Koon Yoong, Azlina Abdul-Aziz, Sarni Mat-Junit, Perumal Subramanian
International Journal of Molecular Sciences. 2022; 23(4): 2093
[Pubmed] | [DOI]
2 The antioxidant icariin protects porcine oocytes from age-related damage in vitro
Jae-Wook Yoon, Seung-Eun Lee, Yun-Gwi Park, Won-Jae Kim, Hyo-Jin Park, Chan-Oh Park, So-Hee Kim, Seung-Hwan Oh, Do-Geon Lee, Da-Bin Pyeon, Eun-Young Kim, Se-Pill Park
Animal Bioscience. 2021; 34(4): 546
[Pubmed] | [DOI]
3 Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines
Margherita Luongo, Oliviero Marinelli, Laura Zeppa, Cristina Aguzzi, Maria Beatrice Morelli, Consuelo Amantini, Andrea Frassineti, Marianne di Costanzo, Alessandro Fanelli, Giorgio Santoni, Massimo Nabissi
Cancers. 2020; 12(10): 2774
[Pubmed] | [DOI]
4 Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma
Guozun Zhang, Dong-Liang Yang, Guoqi Zheng, Yufei Liang
Oncology Letters. 2020;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and Methods>Results>Discussion>Article Figures>Article Tables
  In this article

 Article Access Statistics
    PDF Downloaded105    
    Comments [Add]    
    Cited by others 4    

Recommend this journal