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

 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 7  |  Page : 199-204

Comparison of perioperative outcomes between laparoscopic and open surgery for mid-low rectal cancer with total mesorectal excision following neoadjuvant chemoradiotherapy


1 Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
2 Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
3 Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China

Date of Web Publication21-Feb-2017

Correspondence Address:
Weiping Chen
Department of Colorectal Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang 310022
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200600

Rights and Permissions
 > Abstract 

Objective: The objective of our study was to determine the feasibility and safety of laparoscopic total mesorectal excision (TME) for mid-low rectal cancer following neoadjuvant chemoradiotherapy (nCRT).
Methods: We retrospectively reviewed the records of 172 patients with locally advanced rectal cancer who underwent laparoscopic (n = 75) or conventional open (n = 97) surgery with TME following nCRT from June 2009 to October 2015. Perioperative outcomes and related clinical variables were collected and statistically analyzed.
Results: Our results showed that patients who underwent laparoscopic surgery had significantly less blood loss and shorter time to pass first flatus and to start a liquid diet compared to those on open surgery. However, other perioperative outcomes, including operative times, postoperative morbidity rates, number of lymph nodes harvested, and sphincter preservation rates, were not significantly different between the two groups. After controlling for surgical approaches, we found that age, gender, tumor stages, and tumor distance to anal verge were significantly correlated with operative times in both groups. Likewise, age, body mass index, tumor T stages, and tumor distance to anal verge were predictors for postoperative morbidity in both groups.
Conclusions: We concluded that laparoscopic TME following nCRT is feasible and safe for patients with mid-low rectal cancer. Furthermore, tumor distance to anal verge and age are two important determinants of both operative times and postoperative morbidity, regardless of surgical option.

Keywords: Laparoscopic resection, neoadjuvant chemoradiotherapy, perioperative outcome, rectal cancer


How to cite this article:
Chen W, Li Q, Qiu P, Jiang L, Fu Z, Fan Y, Li D, Liu P, Tang L. Comparison of perioperative outcomes between laparoscopic and open surgery for mid-low rectal cancer with total mesorectal excision following neoadjuvant chemoradiotherapy. J Can Res Ther 2016;12, Suppl S3:199-204

How to cite this URL:
Chen W, Li Q, Qiu P, Jiang L, Fu Z, Fan Y, Li D, Liu P, Tang L. Comparison of perioperative outcomes between laparoscopic and open surgery for mid-low rectal cancer with total mesorectal excision following neoadjuvant chemoradiotherapy. J Can Res Ther [serial online] 2016 [cited 2021 Mar 6];12:199-204. Available from: https://www.cancerjournal.net/text.asp?2016/12/7/199/200600


 > Introduction Top


Colorectal cancer is one of the most frequently diagnosed malignancies and a major cause of cancer death in the US and worldwide.[1],[2] Neoadjuvant chemoradiotherapy (nCRT) followed by surgery with total mesorectal excision (TME) is currently the standard treatment for patients with locally advanced rectal cancer. A reduction in local recurrence rate and an improved survival rate have been achieved with the standard treatment.[3],[4],[5]

Laparoscopic surgery for colorectal cancer has shown short- and long-term oncologic outcomes compared to conventional open surgery.[6],[7],[8],[9] In addition, laparoscopic surgery has clinical advantages such as smaller wound size, less blood loss, faster recovery, and shorter postoperative hospital stays.[6],[10],[11] On the other hand, laparoscopic surgery for mid-low rectal cancer is technically demanding due to the limited pelvic space. Furthermore, nCRT causes tissue edema, fibrosis, and extensive mist and exudates which may impede dissection and further increase the difficulty of laparoscopic resection for mid-low rectal cancer.[12]

Only a few studies have reported the outcomes of laparoscopic TME for mid-low rectal cancer following nCRT. The COREAN trial determined long-term oncogenic outcomes of 340 patients with mid-low advanced rectal cancer who underwent laparoscopic or open surgery (n = 170 each) following nCRT. Their results showed that the laparoscopic group showed improvements in disease-free survival over a 3-year period and other positive long-term oncogenic outcomes.[13] Three other studies reported favorable short-term outcomes of laparoscopic resection for advanced rectal cancer after nCRT.[14],[15],[16],[17],[18] However, results of these studies were still not consistent. In this study, we retrospectively reviewed patients with locally advanced mid-low rectal cancer who underwent fully laparoscopic or open surgery with TME following nCRT. The objective of this study was to investigate the safety and feasibility of laparoscopic resection by comparing perioperative outcomes between these two groups.


 > Methods Top


From June 2009 to October 2015, there were a total of 172 rectal cancer patients who underwent nCRT before surgery with TME at our hospital. All rectal cancers were located 8 cm or less from the anal verge. All patients had stage II or III rectal adenocarcinoma based on sixth or seventh tumor–node–metastasis classification of the Union for International Cancer Control. Patients with rectal cancers of local perforation, obstruction, infiltration to adjacent organs, or distant metastasis were excluded from the study. This study was approved by the Research and Ethics Committee of our hospital. Due to the retrospective nature of the study, informed consent was waived by the committee.

Patients' age, gender, body mass index (BMI), prior abdominal surgery, concurrent diseases (hypertension and/or diabetes), drugs and radiation doses used in preoperative CRT, operative time, morbidity, number of harvested lymph nodes, and tumor staging were collected from their medical records.

Patients received a total of 45–50.4 Gy, 25–28 fractions of 1.8 Gy each, five times per week for 5 weeks. During radiotherapy, patients received twice a day of oral capecitabine 1650 mg/m 2/day. Three weeks after the radiotherapy, patients received one or two cycles of the following chemotherapy: intravenous oxaliplatin 130 mg/m 2 once at the 1st day and twice a day of oral capecitabine 2000 mg/m 2/day for 2 weeks of a 3-week cycle. The mean interval between surgery and the end of nCRT was 60.9 ± 15.1 days for laparoscopic group and 58.9 ± 8.7 days for the open group (P = 0.277).

Statistical analysis

The statistical analysis was performed using SAS software (SAS Institute Inc., Cary, NC, USA). Quantitative data were presented as mean ± standard deviation. Student's t-test, Chi-square test, or Fisher's exact test was applied to examine the difference in variables as indicated. P <0.05 was considered statistically significant.

Operative time and postoperative morbidity are two important perioperative outcomes. To determine which factors predict these, we further analyzed data from the entire study population (both laparoscopic and open surgery groups) through linear or logistic regression models. After univariate analysis, variables with P < 0.25 were selected for multivariate analysis. Multivariate analysis was performed using a stepwise method. All variables of P < 0.15 were included in the multivariate models.


 > Results Top


Among all 172 patients, 75 underwent laparoscopic surgery, and the remaining 97 underwent open surgery. Baseline features for both groups of patients were similar [Table 1].
Table 1: Baseline demographic and clinical features of patients

Click here to view


Perioperative outcomes of both groups are presented in [Table 2]. Our results showed that patients in the laparoscopic group had significantly less blood loss (P = 0.014) and shorter time to pass first flatus (P = 0.007) and to start a liquid diet (P = 0.017) compared to those in the open group. However, neither group showed a significant difference in operative times, number of lymph nodes harvested, proportion of patients who underwent either low anterior resection (LAR) or abdominoperineal resection (APR), and duration of postoperative hospital stay.
Table 2: Perioperative outcomes of patients who underwent laparoscopic or open surgery

Click here to view


The overall morbidity rates were similar between laparoscopic and open surgery group (24.0% vs. 29.9%, respectively; P = 0.390, [Table 2]). These morbidities included wounds, pelvic, perineal, urinary and pulmonary infections, anastomotic bleeding and leak, and intestinal obstruction [Table 3]. No positive longitudinal resection margins were identified. No conversion to open surgery occurred in the laparoscopic group. No patients in either group needed a second operation. No patients died as a result of surgery.
Table 3: Perioperative complications observed

Click here to view


The overall rates of sphincter-sparing surgery (LAR) were 58.7% and 61.9% in laparoscopic and open groups, respectively. Detailed information on sphincter preservation surgery (LAR) based on tumor distance to anal verge is presented in [Table 4]. Of patients with tumor size of 4–5 cm from anal verge, 11 (55.0%) of 20 patients in the laparoscopic group and 26 (63.4%) of 41 patients in the open group underwent sphincter preservation surgery (P = 0.528).
Table 4: Sphincter preservation rates after categorization with tumor distance to anal verge

Click here to view


Linear regression analysis confirmed that the surgical approach (laparoscopic vs. open surgery) was not a factor that contributed to operative time. Univariate analysis revealed that gender (estimate = − 26.9, P = 0.033), surgery styles (LAR or APR) (estimate = 23.7, P = 0.027), prior abdominal surgery (estimate = 32.3, P = 0.028) and tumor distance to anal verge (estimate = − 7.4, P = 0.013) were significantly associated with operative time. Multivariate analysis showed that age (estimate = − 1.1, P = 0.011), gender (estimate = − 31.3, P = 0.031), tumor stages (estimate = 16.9, P = 0.052), and tumor distance to anal verge (estimate = − 5.1, P = 0.023) were predictors for operative time after controlling for surgery approaches [Table 5].
Table 5: Determinants for operative time

Click here to view


Univariate logistic regression analysis showed that BMI estimate = 0.19, P = 0.017) and tumor distance to anal verge (estimate = − 0.41, P = 0.005) were predictors for postoperative morbidity. Multivariate analysis showed that age (estimate= 0.04, P = 0.047), BMI (estimate = 0.18, P = 0.033), tumor T stages (estimate = − 0.63, P = 0.031), and tumor distance to anal verge (estimate = − 0.24, P = 0.043) were significantly associated with morbidity after controlling for surgery approaches [Table 6].
Table 6: Determinants for morbidity

Click here to view



 > Discussion Top


nCRT with curative surgery has been shown to reduce local recurrence and improve survival for rectal cancer patients.[3],[4],[5] However, adverse effects caused by nCRT may increase operative difficulty for rectal cancer surgery, particularly laparoscopic resection. Our results showed that patients who underwent laparoscopic resection had significantly less blood loss and shorter time to pass first flatus and to start liquid diet compared to those underwent open surgery. Other perioperative outcomes were comparable among the two groups. This study provides evidence that it is feasible and safe to perform laparoscopic TME for locally advanced mid-low rectal cancer after nCRT.

For a mid-low rectal cancer patient who undergoes surgery, preservation of anal sphincter significantly improves the quality of the patient's life. nCRT considerably reduces tumor size, downgrades stage, and improves exposure of the surgical field, thus helping to delineate a safe resection margin and increasing the rate of sphincter preservation.[19] Because laparoscopic dissection is performed in a magnified, high-definition view of the deep narrow pelvis, it is also expected to increase the sphincter preservation rate. Indeed, one study reported that sphincter preservation rates were as high as 84.5% (234 of 274) of all patients and 73.1% of patients with tumors ≤5 cm from anal verge who underwent laparoscopic resection after nCRT.[20] A sphincter preservation rate of 91% in laparoscopic group was reported in the COREAN trial.[17] Sphincter preservation rates in laparoscopic surgery cases are much higher than those for open surgery after nCRT [3],[21],[22] but are comparable with other studies.[17],[23] A recent study reported a sphincter preservation rate of 71.4% in rectal cancer patients with tumor size >3 but ≤5 cm from the anal verge in the laparoscopic group after nCRT, which was significantly higher than that of the open surgery group (37.8%). All patients in both groups with tumors ≤3 cm from the anal verge underwent APR.[14] In this study, 55.0% and 63.4% of patients with tumor 4-5 cm from anal verge in laparoscopic and open groups, underwent sphincter preservation surgery (P = 0.528), respectively. No patients in either group with a tumor ≤3 cm from the anal verge underwent sphincter preservation surgery. Data from ours and other groups showed that laparoscopic TME for mid-low rectal cancer after nCRT results in comparable or improved rates of sphincter preservation.

Operative times have been used as an end point to estimate the difficulty of laparoscopic TME for rectal cancer. nCRT has been considered to be a risk factor associated with increased operative times.[24] Previous studies reported that laparoscopic TME for rectal cancer following nCRT resulted in significantly longer operative times than open surgery.[15],[16] In contrast to these studies, Hu et al.[14] and our work presented here revealed that operative times between laparoscopic and open surgery groups are similar. After controlling for surgery approaches (laparoscopic or open surgery), we found that gender, age, tumor stages, and tumor distance from anal verge are associated with operative times with nCRT for the whole study population. These data suggest that laparoscopic TME for mid-low rectal cancer following nCRT can achieve operative times compared to those of open surgery.

The number of lymph nodes harvested was used as an indicator of the adequacy of surgery for colorectal cancer. The number of 12 lymph nodes has been recommended as an indicator of adequacy of surgery for colorectal cancer by the American Joint Committee on Cancer and the International Union against Cancer. We previously reported an average number of 17 harvested lymph nodes in all rectal cancer patients (10% of them received nCRT) who underwent laparoscopic TME.[24] The current study showed an average number of 12–13 harvested lymph nodes in both laparoscopic and open surgery groups following nCRT. The decrease in number of lymph nodes harvested in patients is in accordance with previous reports of decreased lymph nodes harvested following nCRT.[25],[26],[27] A previous study reported a mean number of 11–12 lymph nodes harvested in both laparoscopic and open surgery groups after nCRT.[14] That the recommended number of lymph nodes harvested by laparoscopic TME for mid-low rectal cancer even after nCRT further supports that it is technically safe and feasible.

Although Hu et al.[14] reported reduced morbidity in laparoscopic group compared with open surgery group, we found that the overall morbidity rates were not significantly different (24.0% vs. 29.9%, respectively). Our study also found that age, BMI, tumor T stage, and tumor distance from anal verge were predictors for perioperative morbidity based on logistic regression analysis. nCRT potentially increases the difficulty of laparoscopic resection for mid-low rectal cancer, and varied rates (1.2%–32%) of conversion from laparoscopic to open surgery following nCRT have been reported in previous studies.[14],[17],[28],[29] No conversion to open surgery occurred in our patients who underwent laparoscopic TME after nCRT. The low morbidity rate, compared to that of the open surgery group, coupled with the finding that none of the patients in the laparoscopic group required subsequent open surgery in our study further supports the assertion that laparoscopic TME for mid-low rectal cancer is feasible and safe.

Our study has several limitations. This is a retrospective study with no randomization. All data included in this study are from a single hospital. Only 30.8% of the patients in our study were female although the incidence of male and female rectal cancer patients is similar in China.[30] The average of our patients' BMI is much lower than that of populations in Western countries, but it is comparable to those of Chinese colorectal cancer patients reported in a recent study.[2] Long-term effects were not addressed in this study. Despite these limitations, this study provides strong evidence that demonstrates the feasibility and safety of laparoscopic TME for mid-low rectal cancer.


 > Conclusion Top


A few studies have compared perioperative outcomes of laparoscopic TME for mid-low rectal cancer following nCRT with those of open surgery.[15],[16],[17] Our results suggest that laparoscopic surgery has perioperative outcomes that are comparable or better than those of open surgery. Furthermore, tumor distance to anal verge and age are two important determinants of both operative times and postoperative morbidity, regardless of surgical approaches.

Financial support and sponsorship

This work is supported by the Zhejiang Medical Technology and Education (2011RCA010).

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.  Back to cited text no. 1
    
2.
Liu S, Zheng R, Zhang M, Zhang S, Sun X, Chen W. Incidence and mortality of colorectal cancer in China, 2011. Chin J Cancer Res 2015;27:22-8.  Back to cited text no. 2
    
3.
Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-40.  Back to cited text no. 3
    
4.
Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: Long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005;23:5644-50.  Back to cited text no. 4
    
5.
Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, et al. The TME trial after a median follow-up of 6 years: Increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg 2007;246:693-701.  Back to cited text no. 5
    
6.
Nussbaum DP, Speicher PJ, Ganapathi AM, Englum BR, Keenan JE, Mantyh CR, et al. Laparoscopic versus open low anterior resection for rectal cancer: Results from the national cancer data base. J Gastrointest Surg 2015;19:124-31.  Back to cited text no. 6
    
7.
Lacy AM, García-Valdecasas JC, Delgado S, Castells A, Taurá P, Piqué JM, et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: A randomised trial. Lancet 2002;359:2224-9.  Back to cited text no. 7
    
8.
Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004;350:2050-9.  Back to cited text no. 8
    
9.
Leung KL, Kwok SP, Lam SC, Lee JF, Yiu RY, Ng SS, et al. Laparoscopic resection of rectosigmoid carcinoma: Prospective randomised trial. Lancet 2004;363:1187-92.  Back to cited text no. 9
    
10.
Laurent C, Leblanc F, Wütrich P, Scheffler M, Rullier E. Laparoscopic versus open surgery for rectal cancer: Long-term oncologic results. Ann Surg 2009;250:54-61.  Back to cited text no. 10
    
11.
Zhang FW, Zhou ZY, Wang HL, Zhang JX, Di BS, Huang WH, et al. Laparoscopic versus open surgery for rectal cancer: A systematic review and meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev 2014;15:9985-96.  Back to cited text no. 11
    
12.
Ishihara S, Watanabe T, Fukushima Y, Akahane T, Horiuchi A, Shimada R, et al. Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy. Tech Coloproctol 2014;18:247-55.  Back to cited text no. 12
    
13.
Jeong SY, Park JW, Nam BH, Kim S, Kang SB, Lim SB, et al. Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): Survival outcomes of an open-label, non-inferiority, randomised controlled trial. Lancet Oncol 2014;15:767-74.  Back to cited text no. 13
    
14.
Hu JJ, Liang JW, Wang Z, Zhang XM, Zhou HT, Hou HR, et al. Short-term outcomes of laparoscopically assisted surgery for rectal cancer following neoadjuvant chemoradiotherapy: A single-center experience. J Surg Res 2014;187:438-44.  Back to cited text no. 14
    
15.
Denoya P, Wang H, Sands D, Nogueras J, Weiss E, Wexner SD. Short-term outcomes of laparoscopic total mesorectal excision following neoadjuvant chemoradiotherapy. Surg Endosc 2010;24:933-8.  Back to cited text no. 15
    
16.
Seshadri RA, Srinivasan A, Tapkire R, Swaminathan R. Laparoscopic versus open surgery for rectal cancer after neoadjuvant chemoradiation: A matched case-control study of short-term outcomes. Surg Endosc 2012;26:154-61.  Back to cited text no. 16
    
17.
Kang SB, Park JW, Jeong SY, Nam BH, Choi HS, Kim DW, et al. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): Short-term outcomes of an open-label randomised controlled trial. Lancet Oncol 2010;11:637-45.  Back to cited text no. 17
    
18.
Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M, et al. Effect of laparoscopic-assisted resection vs. open resection of stage II or III rectal cancer on pathologic outcomes: The ACOSOG Z6051 randomized clinical trial. JAMA 2015;314:1346-55.  Back to cited text no. 18
    
19.
Ishihara S, Hayama T, Yamada H, Nozawa K, Matsuda K, Watanabe T. Benefit of tegafur-uracil and leucovorin in chemoradiotherapy for rectal cancer. Hepatogastroenterology 2011;58:756-62.  Back to cited text no. 19
    
20.
Lee JH, Kim SH, Kim JG, Cho HM, Shim BY. Preoperative chemoradiotherapy (CRT) followed by laparoscopic surgery for rectal cancer: Predictors of the tumor response and the long-term oncologic outcomes. Int J Radiat Oncol Biol Phys 2011;81:431-8.  Back to cited text no. 20
    
21.
Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: Preliminary results – EORTC 22921. J Clin Oncol 2005;23:5620-7.  Back to cited text no. 21
    
22.
Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: Results of FFCD 9203. J Clin Oncol 2006;24:4620-5.  Back to cited text no. 22
    
23.
Ulrich A, Weitz J, Slodczyk M, Koch M, Jaeger D, Münter M, et al. Neoadjuvant treatment does not influence perioperative outcome in rectal cancer surgery. Int J Radiat Oncol Biol Phys 2009;75:129-36.  Back to cited text no. 23
    
24.
Chen W, Li Q, Fan Y, Li D, Jiang L, Qiu P, et al. Factors predicting difficulty of laparoscopic low anterior resection for rectal cancer with total mesorectal excision and double stapling technique. PLoS One 2016;11:e0151773.  Back to cited text no. 24
    
25.
Wijesuriya RE, Deen KI, Hewavisenthi J, Balawardana J, Perera M. Neoadjuvant therapy for rectal cancer down-stages the tumor but reduces lymph node harvest significantly. Surg Today 2005;35:442-5.  Back to cited text no. 25
    
26.
Kim YW, Kim NK, Min BS, Lee KY, Sohn SK, Cho CH, et al. The prognostic impact of the number of lymph nodes retrieved after neoadjuvant chemoradiotherapy with mesorectal excision for rectal cancer. J Surg Oncol 2009;100:1-7.  Back to cited text no. 26
    
27.
Marks JH, Valsdottir EB, Rather AA, Nweze IC, Newman DA, Chernick MR. Fewer than 12 lymph nodes can be expected in a surgical specimen after high-dose chemoradiation therapy for rectal cancer. Dis Colon Rectum 2010;53:1023-9.  Back to cited text no. 27
    
28.
Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): Multicentre, randomised controlled trial. Lancet 2005;365:1718-26.  Back to cited text no. 28
    
29.
Tsang WW, Chung CC, Kwok SY, Li MK. Laparoscopic sphincter-preserving total mesorectal excision with colonic J-pouch reconstruction: Five-year results. Ann Surg 2006;243:353-8.  Back to cited text no. 29
    
30.
Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev 2009;18:1688-94.  Back to cited text no. 30
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
 
 
  Search
 
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>Methods>Results>Discussion>Conclusion>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed1613    
    Printed25    
    Emailed0    
    PDF Downloaded135    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]