• Users Online: 226
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 7-14

A tale of two pathologies: Multidisciplinary team approach to a second pathology synchronous to gastrointestinal tumors


1 Department of Gastrointestinal Oncosurgery, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
2 Department of Radiation Oncology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
3 Department of Nuclear Medicine, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
4 Department of Radiology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
5 Department of Pathology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
6 Department of Medical Oncology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India

Date of Submission16-May-2021
Date of Decision16-Aug-2021
Date of Acceptance12-Oct-2021
Date of Web Publication01-Jan-2022

Correspondence Address:
M N Saravanan
Apollo Proton Cancer Centre, 4/661, Dr. Vikram Sarabai Instronic Estate, 7th Street, Taramani Road, Chennai - 600 041, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ghep.ghep_23_21

Rights and Permissions
  Abstract 


Background: In workup for a tumor in an individual, a second pathology is discovered at times, which can complicate further management. Cross-sectional imaging is widely utilized in gastrointestinal tumors leading to identification of incidentalomas, and we audited our multidisciplinary team (MDT) meeting data in order to analyze the implications and refine the approach in the presence of dual pathology. Materials and Methods: This study was a retrospective assessment of a prospectively maintained single institute gastrointestinal tumor board MDT database between June 2019 and June 2020. Results: Of the 76 patients discussed in the gastrointestinal MDT, 21 patients associated with clinically relevant second pathology were included in the study group. Positron emission tomography–computed tomography (PET-CT) was the most common modality responsible for detection of the second pathology. Additional workup to better characterize these findings was needed in 10 (47.6%) patients. Eleven patients had dual neoplasms, of which four accounted for dual malignant neoplasms. MDT resulted in a change in plan in 6 (28.6%) patients, which was mainly related to radiology review, thereby downstaging to the correct stage. Conclusions: PET-CT increases detection of a second pathology in gastrointestinal tumors. Appropriate review of radiology, supplementing with additional imaging and/or biopsy, and wait and reassess in selected situations in an MDT is pivotal in management of a double pathology.

Keywords: Dual pathology, incidentaloma, multidisciplinary team meeting, synchronous tumors


How to cite this article:
Saravanan M N, Vaithiswaran V, Mathew AS, Sundaraiya S, Sulaiman A, Rajendran A, Patil S, Chilukuri S, Nangia S, Raja T. A tale of two pathologies: Multidisciplinary team approach to a second pathology synchronous to gastrointestinal tumors. Gastroenterol Hepatol Endosc Pract 2022;2:7-14

How to cite this URL:
Saravanan M N, Vaithiswaran V, Mathew AS, Sundaraiya S, Sulaiman A, Rajendran A, Patil S, Chilukuri S, Nangia S, Raja T. A tale of two pathologies: Multidisciplinary team approach to a second pathology synchronous to gastrointestinal tumors. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 Aug 18];2:7-14. Available from: http://www.ghepjournal.com/text.asp?2022/2/1/7/334695




  Introduction Top


The presence of dual pathology within a patient complicates the approach in terms of both diagnosis and therapy. Searching “dual pathology” in medical literature yields results only in two contexts. One of these is in the context of neurology where a dual pathology refers to the association of hippocampal atrophy with an extrahippocampal lesion producing epilepsy.[1] The other place where the term is used is in mental health to refer to patients who suffer from an addictive disorder and other mental disorders.[2]

Dual pathology in the context of tumors has a prognostic implication as to whether one or both of the tumors are malignant. Double cancer (synchronous and metachronous) and “incidentalomas” have been reported in the context of tumors, especially with widespread use of cross-sectional imaging. Simultaneous detection of another pathology can cause result in delay in treatment due to ambiguity in diagnosis and decision-making, financial implications, and stress to the patient and kins. The role of multidisciplinary team (MDT) meeting discussion can be crucial for guiding further management in such scenarios. We analyzed the database of gastrointestinal cancer MDT between June 2019 and June 2020 at our institute, to identify cases with a second pathology and assessed the impact on further course of management.


  Materials and Methods Top


Gastrointestinal cancer MDT proceedings were recorded in a prospective database since June 2019 at our institute. The MDT comprised surgeon, medical oncologist, radiation oncologist, radiologist, nuclear medicine physician, pathologist, and other allied professionals. All patients in whom, in addition to the primary tumor site, there was additional pathology demonstrable by clinical examination, radiological investigations, and endoscopy were assessed in the period between June 2019 and June 2020. Demography, location, clinical findings, imaging characteristics on ultrasound (US), computed tomography (CT), positron emission tomography (PET) CT, magnetic resonance imaging (MRI), features on endoscopy, pathology including frozen section, MDT discussion, and treatment implication and follow up were retrieved from the database and assessed. Patients with disseminated and frankly metastatic disease and those with simple liver and renal cysts, calcific granuloma, overtly benign pathology (nontumor), and imaging artifacts were excluded from the final analysis. Patients with long-standing incidentaloma or pathology, which were known prior to the diagnosis of the primary tumor, were not included. The secondary lesion therefore consisted of benign tumors or pathology with suspicion of malignancy, with discordance in opinion and/or warranted additional investigation or follow-up to characterize the nature of disease. Implications in final management were assessed.


  Results Top


Out of 76 patients discussed in the gastrointestinal cancer MDT, 43 patients had synchronous second pathology in the backdrop of primary gastrointestinal tumor. Of these, 22 patients were excluded and 21 patients formed the study group [Table 1].
Table 1: Primary and secondary pathology, additional investigation needed and final diagnosis with implication

Click here to view


Of the 22 patients excluded, 7 patients had frank or disseminated metastases. Apart from the metastatic disease, these patients had 27 additional pathologies which were overtly nontumorous. Concomitant surgery was needed in three patients from the excluded group. These included laparoscopic cholecystectomy, endoscopic ureteroscopy, and ureteric stenting for symptomatic gall stones, ureteric calculus, and ureteric obstruction by nodal metastasis, respectively.

Patients in the study group did not show any gender difference (females = 11 and males = 10). The mean age of the study group was 58.09 years (median: 61, interquartile range: 50–66 years). The most common primary site of tumor was colorectal (42.9%) followed by pancreas/ampullary [Table 2]. All primary pathology was cancer except two which were benign with low-to-intermediate malignant potential (solitary papillary neoplasm pancreas and abdominal desmoid).
Table 2: Characteristics of study group

Click here to view


Of the 21 patients in the study group, 4 patients had more than one associated pathology. These contributed to eight additional pathologies, all of which were nontumor and did not have any clinical impact. Liver and lung were the most common sites of second pathology attributing to 42.9% of all significantly associated pathologies.

Various modalities which detected the associated second pathology are shown in the graph [Figure 1]. PET-CT and CT scan were the most common modalities which detected additional pathology/pathologies. Additional workup to better characterize these findings was needed in 10 (47.6%) patients. Two of these 10 patients needed 2 investigations each (MRI and PET-CT; laparoscopy and biopsy), with an overall need to perform 12 modalities for workup in 10 patients. All but one of these additional modalities was contemplated in the MDT. In one patient, in view of intraoperatively encountered nodules over the liver surface, intraoperative decision to proceed with frozen section assessment was taken, which was reported as benign and was eventually consistent with biliary hamartoma. Imaging mainly consisted of US (2), CT (2), MRI (2), or PET-CT (1). In one patient with cystic neoplasm of pancreas, CT was needed for both better characterization of the primary pancreatic pathology and the additional adnexal pathology. Laparoscopic assessment with biopsy was needed in one patient to distinguish between pelvic deposits and inflammation.
Figure 1: Diagnostic modality that identified the second pathology

Click here to view


Of the 21 patients in the study group, dual neoplasms were seen in 11 cases. Dual malignancy accounted for 4 of these 11 cases, contributing to 5.3% of the 76 cases discussed in the gastrointestinal MDT. The remaining seven cases had benign tumors as second pathology with two of these having a risk of malignant transformation (ovarian teratoma and sigmoid polyp). The double cancers were treated by concurrent or staged surgery/procedure or multimodality therapy. Patients with double cancers were advised genetic testing after counseling. Two of the four patients underwent limited panel testing (Oncomine focus assay and microsatellite instability testing by immunohistochemistry), and no mutations were detected in them.

The initial diagnosis and final diagnosis of the second significant pathology are represented in [Figure 2]. Further to MDT discussion and workup, there was a change in plan in 6 (28.6%) patients. Change in plan was related to imaging (83.3%) more often. Change in interpretation of radiology was to the tune of 23.8% in the 21 patients. Of these, the secondary pathology was addressed in two patients and not treated in the remaining four patients. Overall, of the 21 patients, the secondary pathology was treated in 6 (28.6%) patients and not treated in 14 (66.7%) patients and 1 patient was lost to follow-up.
Figure 2: Change in diagnosis after workup

Click here to view



  Discussion Top


The incidence of incidentaloma has steadily risen with the increasing advent of use, ease of availability, and refinement in imaging [Figure 3]a and [Figure 3]b. The prevalence varies according to the modality utilized.[3] Pulmonary nodules have been identified in up to 25% of individuals examined by CT chest.[4] The incidence of incidental focal thyroid lesions varies from 1% to 5% on PET scan, with F18-fluorodeoxyglucose (FDG) avidity failing to distinguish between benign and malignant lesions.[5] PET-CT scan has become one of the most frequently used staging modalities, when it is easily available. It is therefore not very surprising that PET-CT picked up most of the additional pathologies in our study. Whenever a second pathology is encountered in the setting of a primary neoplasm, myriad issues related to diagnosis and decision-making arise, which significantly influence outcomes and cost and can result in anxiety [Table 3].
Figure 3: (a) Computed tomography showing pancreatic cystic neoplasm (yellow circle) and ovarian dermoid (white circle); (b) computed tomography showing descending colon growth (yellow arrow) with pancreatic lipoma (orange circle); (c) computed tomography in a patient with pelvic leiomyosarcoma showing a suspicious hypodense lesion in liver (green circle); (d) contrast magnetic resonance of the same patient as c, showing delayed enhancement of central scar suggestive of focal nodular hyperplasia (red arrow)

Click here to view
Table 3: Key issues in addressing a significant second pathology

Click here to view


The downside to detecting indolent secondary lesions is the risk of overtreating them. Treatment modalities are not without a finite risk of complications. Labeling these low-grade tumors which are inconsequential as “indolent lesions of epithelial origin” or IDLE has been advocated to avoid unnecessary anxiety. Such lesions are more commonly reported in breast, lung, prostate, and thyroid. Early detection by screening and removal of premalignant conditions have not always led to the decrease in incidence of invasive cancer across all pathologies. Understanding the dynamics and biology of the incidentaloma including by molecular means can help identify the subgroup of indolent lesions, thus allaying apprehension, avoiding overtreatment, and optimizing resource allocation.[6]

Double primary cancers have been audited in the past as early as in 1932.[7],[8] Most of these were in the metachronous setting and mainly in the context of head-and-neck cancers.[9],[10],[11],[12],[13],[14] The prevalence of multiple primary malignancies has ranged from 0.73% to 11.7%.[15] The incidence of double cancers in a possibly more selected cohort that we encountered, was around 5% (4 out of 76 cases discussed in gastrointestinal MDT). The second malignancy has been attributed to various factors including field cancerization, genetic susceptibility, immune mechanism, exposure, or treatment-related sequelae.[9] Mutation in multiple tumor suppressor genes such as p16, p53, PTEN, and Rb gene is linked to development of tumors in breast, soft tissue, esophagus, and other sites.[11] Microsatellite instability has been implicated in the presence of multiple cancers.[16]

The presence of dual cancer may not always portend a poorer outcome, as prognosis may be independent of the concurrent presence of tumors. The prognosis, prioritization, use of multimodality therapy, and any collateral benefit due to chemotherapy need discussion in a multidisciplinary fashion, since data for treatment and outcomes for such associations are scarce.[13] It is important to define the prognosis based on each tumor's stage and assess the magnitude of possible combined surgery and the fitness of the individual to withstand the same.[17] If proceeding with curative intent treatment, whether to offer simultaneous therapy to both sites with potential of additional morbidity, or to offer treatment in a staged manner with an acceptable risk of progression in the interim period, needs deliberation in an MDT setting.

The advantage of MDT is in its systematic understanding of the clinical background in addition to serial assessment of all images available for comparison. When imaging is reported in isolation, the final impression is often found to be noncommittal.[18] MDT ensures efficient analysis of data and facilitates good coordination and information sharing.[19] MDT is not without its set of loopholes. In the presence of disagreement between MDT participants, whether to present this to the patient or not has been debated and how to offer choices to the patient without introducing any bias by the primary consultant is a challenge.[20] Failure to discuss a subset of patients in MDT and failing to implement the MDT decision also has been highlighted. The team members of any new MDT need time to integrate their views and go through a learning curve as well. MDT implementation rates have ranged from 83% to 93.6% in colorectal cancer.[21],[22],[23] The benefit of MDT has been felt more in advanced cancers than in early-stage disease.[21]

Change in clinical decision was reported in over 10% of 1383 cases in a colorectal MDT at a Korean center.[24] Radiology review contributed to about 47% of change in decision in their experience. We reported a change in plan in up to 28% of patients, with review of radiology accounting for over 83% of change in decisions with overall imaging interpretation changing in 24% cases, which is high. This reflects the small sample size, highly selected cohort of dual pathologies as well as the influence of quality of initial radiology and its reporting (as often we receive imaging performed and reported elsewhere). A head-and-neck cancer MDT reported a 27% change in tumor diagnosis, stage, or treatment plan in 27% of the 120 patients studied.[25] While another head-and-neck cancer MDT reported a change in interpretation in imaging in 41% of 136 patients studied.[26] Both these studies from American centers focused on head-and-neck cancer also reveal a higher rate of changes in diagnosis and treatment when the denominator is smaller, like in our study.

Whenever the characterization of a second pathology is not feasible on the modality which detects it, the options available include a better or complementary cross-sectional imaging or an attempt to perform a tissue diagnosis. CT and MRI have been complementary to each other [Figure 3]c and [Figure 3]d. Contrast enhancement patterns, diffusion restriction to assess cellularity in MRI, and fusion with PET often help to indicate a higher or lower probability of whether we are dealing with a benign or a malignant lesion, if in case, it does not clinch the diagnosis. The choice between the two depends upon the size and location of lesion, certainty of the suspected diagnosis, accessibility and risks involved in biopsy, and the potential impact it can have on the way forward. When additional imaging fails to conclusively establish the diagnosis and biopsy is not possible, options are between wait and watch and empirically treating it. Indeterminate pulmonary lesions were the most commonly observed second pathology in our study group. When pulmonary lesions are small with imperceptible F18-FDG uptake, more than the number of lesions, close imaging follow-up, or tissue diagnosis has been thought to be important, especially in the absence of concurrent benign lung pathology.[27] Risks involved in subjecting lung lesions to biopsy include bleeding (1%) and clinically significant pneumothorax (6.6%).[4] Hence, it may be prudent to serially reassess, unless it has a strong bearing on outcomes and decision-making. The final decision is likely to not only bear the influence of the learning curve of the MDT but also the patient preference and a certain bias introduced by the primary physician who interacts with the patient. These are difficult to be captured in an MDT pro forma [Figure 5].
Figure 4: Algorithmic approach to second pathology synchronous to gastrointestinal tumor. *Malignant potential and ability to cause significant symptoms or complications. #Size and location of lesion, feasibility of biopsy, likely clinical impact on outcomes

Click here to view
Figure 5: Multidisciplinary proforma for patients with gastrointestinal tumor

Click here to view


What could have falsely directed the treatment in a palliative direction, was downstaged by MDT and/or pursuant workup in 6 of our patients. With the increasing fear of missing a cancer, heightened awareness, and screening strategies, the incidence of overdiagnosis is bound to increase. Until such time that variability in reporting standards pertaining to radiology exists and the learning curve of radiologists continues, understaging or overstaging will continue. Nearly one-fourth of the patients in our study group had issues related to interpretation of radiology.

The first step on encountering a second lesion is to rule out metastasis. We needed an additional modality of investigation in nearly half of the patients, after having excluded metastases. The next step is to ascertain the malignant potential of the second lesion and other high-risk features including propensity to produce any symptoms or complications, discuss outcomes, and prioritize treatment. If both the tumors are malignant, then genetic counseling and workup for a familial syndrome should be considered. We make it a point to discuss the follow-up in the MDT to provide feedback to all participants and enable learning. The algorithmic approach for a second pathology detected that shaped in our MDT is summarized in [Figure 4].


  Conclusions Top


This study alludes to the pragmatic role played by a dedicated MDT in decoding an incidentaloma in the setting of gastrointestinal tumors, which makes it complex due to diagnostic, prognostic, and intent of treatment implications. Advances in imaging and extensive use of cross-sectional scans will certainly increase detection of a second pathology, in not only the context of gastrointestinal tumors but also across all pathologies. Clinicoradiological correlation, serial comparison of imaging, selectively supplementing with additional imaging, and/or tissue diagnosis is imperative in characterizing a second pathology discovered incidentally.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lévesque MF, Nakasato N, Vinters HV, Babb TL. Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: The problem of dual pathology. J Neurosurg 1991;75:364-70.  Back to cited text no. 1
    
2.
Szerman N, Martinez-Raga J, Peris L, Roncero C, Basurte I, Vega P, et al. Rethinking dual disorders/pathology. Addict Disord Treat 2013;12:1-10.  Back to cited text no. 2
    
3.
Booth TC, Jackson A, Wardlaw JM, Taylor SA, Waldman AD. Incidental findings found in “healthy” volunteers during imaging performed for research: Current legal and ethical implications. Br J Radiol 2010;83:456-65.  Back to cited text no. 3
    
4.
Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: An analysis of discharge records. Ann Intern Med 2011;155:137-44.  Back to cited text no. 4
    
5.
Eloy JA, Brett EM, Fatterpekar GM, Kostakoglu L, Som PM, Desai SC, et al. The significance and management of incidental [18F] fluorodeoxyglucose-positron-emission tomography uptake in the thyroid gland in patients with cancer. AJNR Am J Neuroradiol 2009;30:1431-4.  Back to cited text no. 5
    
6.
Esserman LJ, Thompson IM Jr., Reid B. Overdiagnosis and overtreatment in cancer: An opportunity for improvement. JAMA 2013;310:797-8.  Back to cited text no. 6
    
7.
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.  Back to cited text no. 7
    
8.
Bugher JC. The probability of the chance occurrence of multiple malignant neoplasms. Am J Cancer 1934;21:2309-824.  Back to cited text no. 8
    
9.
Bagri PK, Singh D, Singhal MK, Singh G, Mathur G, Jakhar SL, et al. Double primary malignancies: A clinical and pathological analysis report from a regional cancer institute in India. Iran J Cancer Prev 2014;7:66-72.  Back to cited text no. 9
    
10.
Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: Subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29:739-46.  Back to cited text no. 10
    
11.
Hulikal N, Ray S, Thomas J, Fernandes DJ. Second primary malignant neoplasms: A clinicopathological analysis from a cancer centre in India. Asian Pac J Cancer Prev 2012;13:6087-91.  Back to cited text no. 11
    
12.
Gursel B, Meydan D, Özbek N, Ozdemir O, Odabas E. Multiple primary malignant neoplasms from the black sea region of Turkey. J Int Med Res 2011;39:667-74.  Back to cited text no. 12
    
13.
Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple primary malignancies – Epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.  Back to cited text no. 13
    
14.
Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Makoshi T, et al. Multiple primary malignancies in the head and neck: A clinical review of 121 patients. Acta Otolaryngol Suppl 2002;122:88-92.  Back to cited text no. 14
    
15.
Demandante CG, Troyer DA, Miles TP. Multiple primary malignant neoplasms: Case report and a comprehensive review of the literature. Am J Clin Oncol 2003;26:79-83.  Back to cited text no. 15
    
16.
Horii A, Han HJ, Shimada M, Yanagisawa A, Kato Y, Ohta H, et al. Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res 1994;54:3373-5.  Back to cited text no. 16
    
17.
Taniai T, Haruki K, Shiba H, Onda S, Sakamoto T, Yanaga K. Simultaneous resection for synchronous double primary cancers of the pancreas and the liver. Case Rep Gastroenterol 2018;12:504-12.  Back to cited text no. 17
    
18.
Fergusson J. Investigation and management of hepatic incidentalomas. J Gastroenterol Hepatol 2012;27:1772-82.  Back to cited text no. 18
    
19.
Silbermann M, Pitsillides B, Al-Alfi N, Omran S, Al-Jabri K, Elshamy K, et al. Multidisciplinary care team for cancer patients and its implementation in several Middle Eastern countries. Ann Oncol 2013;24 Suppl 7:vii41-7.  Back to cited text no. 19
    
20.
Hamilton DW, Heaven B, Thomson RG, Wilson JA, Exley C. Multidisciplinary team decision-making in cancer and the absent patient: A qualitative study. BMJ Open 2016;6:e012559.  Back to cited text no. 20
    
21.
Munro A, Brown M, Niblock P, Steele R, Carey F. Do Multidisciplinary Team (MDT) processes influence survival in patients with colorectal cancer? A population-based experience. BMC Cancer 2015;15:686.  Back to cited text no. 21
    
22.
Chinai N, Bintcliffe F, Armstrong EM, Teape J, Jones BM, Hosie KB. Does every patient need to be discussed at a multidisciplinary team meeting? Clin Radiol 2013;68:780-4.  Back to cited text no. 22
    
23.
Wood JJ, Metcalfe C, Paes A, Sylvester P, Durdey P, Thomas MG, et al. An evaluation of treatment decisions at a colorectal cancer multi-disciplinary team. Colorectal Dis 2008;10:769-72.  Back to cited text no. 23
    
24.
Jung SM, Hong YS, Kim TW, Park JH, Kim JH, Park SH, et al. Impact of a multidisciplinary team approach for managing advanced and recurrent colorectal cancer. World J Surg 2018;42:2227-33.  Back to cited text no. 24
    
25.
Wheless SA, McKinney KA, Zanation AM. A prospective study of the clinical impact of a multidisciplinary head and neck tumor board. Otolaryngol Head Neck Surg 2010;143:650-4.  Back to cited text no. 25
    
26.
Loevner LA, Sonners AI, Schulman BJ, Slawek K, Weber RS, Rosenthal DI, et al. Reinterpretation of cross-sectional images in patients with head and neck cancer in the setting of a multidisciplinary cancer center. AJNR Am J Neuroradiol 2002;23:1622-6.  Back to cited text no. 26
    
27.
O JH, Yoo IeR, Kim SH, Sohn HS, Chung SK. Clinical significance of small pulmonary nodules with little or no 18F-FDG uptake on PET/CT images of patients with nonthoracic malignancies. J Nucl Med 2007;48:15-21.  Back to cited text no. 27
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed712    
    Printed80    
    Emailed0    
    PDF Downloaded59    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]