+ All Categories
Home > Documents > Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

Date post: 27-Dec-2016
Category:
Upload: rani
View: 216 times
Download: 0 times
Share this document with a friend
4
CASE REPORT OPEN ACCESS International Journal of Surgery Case Reports 4 (2013) 58–61 Contents lists available at SciVerse ScienceDirect International Journal of Surgery Case Reports j ourna l ho me pa ge: www.elsevier.com/locate/ijscr Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas Mehala Tharmabala , Rani Kanthan Department of Pathology and Laboratory Medicine, University of Saskatchewan, Canada a r t i c l e i n f o Article history: Received 4 May 2012 Received in revised form 24 September 2012 Accepted 3 October 2012 Available online 11 October 2012 Keywords: Thyroid papillary carcinoma Thyroglossal duct cyst Thyroglossal duct remnants Management guidelines Risk stratification a b s t r a c t INTRODUCTION: Benign thyroglossal duct tract remnants typically thyroglossal duct cysts, (TDCs) are one of the commonest congenital childhood midline neck masses. Clinical presentation of persistent TDCs in adults is uncommon and the occurrence of incidental primary thyroid papillary carcinoma (TPC) in these cysts is rare. PRESENTATION OF CASE: We report the case of a 32-year-old female with an asymptomatic midline neck mass compatible with a TDC that was excised by Sistrunk’s procedure. Histopathological examination revealed an incidental primary intraluminal TPC arising from the wall of the TDC. DISCUSSION: Management dilemmas regarding the roles for total thyroidectomy, regional lymph node dissection, radioactive iodine, and suppressive thyroxine therapy are reviewed in the context of relevant evidence based literature. CONCLUSION: The occurrence of incidental TPC in a TDC is rare. Though Sistrunk’s procedure is adequate treatment for TDC, based on low, moderate, and high risk stratification, recommendations for further management of incidental TPC in TDC is discussed. © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. 1. Introduction TDCs are one of the most common (75%) asymptomatic mid- line congenital neck masses in childhood. 1–3 Persistent TDCs occur rarely (7%) in adults. 1,3,4 Amongst all cancers, thyroid carcinoma is relatively uncommon (2%). 5 Reported cases of thyroid carcinomas occurring in TDC are extremely uncommon (1–2%). 1–3,6,7 Though described in 1911 by Brentano, the first reported case in the English literature of a primary TPC in a TDC is by Owen and Ingelby in 1927. 1,3,7 Controversies exist even today regarding: (a) exact origin and (b) optimal management for incidental TPC in TDC. 1–3,7–9 Majority of TPCs in TDCs are discovered as an incidental find- ing on pathological examination of the excised cyst specimen treated by Sistrunk’s procedure based on the embryological devel- opment of the thyroid gland. 9–13 Simple local excision of TDC is no longer advised due to recurrences related to incomplete removal of the thyroglossal tract. 1,9 The rare discovery of an incidental TPC in a TDC raises questions regarding best practice guidelines for further management which still remains controversial and debatable. 1,9,13,14 We report the case of an incidental primary intraluminal well- differentiated TPC arising in a TDC and discuss the potential roles for Corresponding author at: 4681 Maple Grove Rd, Beamsville, ON, Canada. Tel.: +1 905 683 0469; fax: +1 905 562 0914. E-mail addresses: [email protected] (M. Tharmabala), [email protected] (R. Kanthan). total thyroidectomy, regional lymph-node dissection, radioactive iodine, and suppressive thyroxine therapy as adjuvant therapy in the context of relevant evidence-based literature. 2. Presentation of case 2.1. Case report A 32-year-old female who presented with a painless 3 cm swelling in the anterior aspect of the neck, clinically compatible with a TDC was treated by a standard Sistrunk’s procedure. Histopathological examination showed the presence of 0.8 cm papillary neoplasm arising from the cyst wall which contained entrapped thyroid follicles in keeping with a TDC (Fig. 1a). Microscopic examination of the papillary neoplasm showed the presence of complex fibrovascular cores lined by epithelium with characteristic nuclear features of well-differentiated low grade TPC (Fig. 1b). No additional histological subtypes were identified. Immunohistochemical staining with antibodies to low molecular weight keratin, thyroid transcription factor-1 (TTF-1), and thy- roglobulin were strongly positive both in the papillary neoplasm and the residual trapped non-neoplastic thyroid follicles (Fig. 1c). The TPC arising in the TDC was completely excised with no evi- dence of invasion of the underlying cyst wall. No further surgical treatment was undertaken as this was considered an incidental well-differentiated classical thyroid papillary microcarcinoma. 1-year follow up was unremarkable. 2210-2612/$ see front matter © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijscr.2012.10.003
Transcript
Page 1: Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

Id

MD

a

ARR2AA

KTTTMR

1

lrro

ia(T

itoloTfd

d

T

r

2h

CASE REPORT – OPEN ACCESSInternational Journal of Surgery Case Reports 4 (2013) 58– 61

Contents lists available at SciVerse ScienceDirect

International Journal of Surgery Case Reports

j ourna l ho me pa ge: www.elsev ier .com/ locate / i j scr

ncidental thyroid papillary carcinoma in a thyroglossal duct cyst – managementilemmas

ehala Tharmabala ∗, Rani Kanthanepartment of Pathology and Laboratory Medicine, University of Saskatchewan, Canada

r t i c l e i n f o

rticle history:eceived 4 May 2012eceived in revised form4 September 2012ccepted 3 October 2012vailable online 11 October 2012

eywords:

a b s t r a c t

INTRODUCTION: Benign thyroglossal duct tract remnants typically thyroglossal duct cysts, (TDCs) are oneof the commonest congenital childhood midline neck masses. Clinical presentation of persistent TDCs inadults is uncommon and the occurrence of incidental primary thyroid papillary carcinoma (TPC) in thesecysts is rare.PRESENTATION OF CASE: We report the case of a 32-year-old female with an asymptomatic midline neckmass compatible with a TDC that was excised by Sistrunk’s procedure. Histopathological examinationrevealed an incidental primary intraluminal TPC arising from the wall of the TDC.

hyroid papillary carcinomahyroglossal duct cysthyroglossal duct remnantsanagement guidelines

isk stratification

DISCUSSION: Management dilemmas regarding the roles for total thyroidectomy, regional lymph nodedissection, radioactive iodine, and suppressive thyroxine therapy are reviewed in the context of relevantevidence based literature.CONCLUSION: The occurrence of incidental TPC in a TDC is rare. Though Sistrunk’s procedure is adequatetreatment for TDC, based on low, moderate, and high risk stratification, recommendations for furthermanagement of incidental TPC in TDC is discussed.

© 2

. Introduction

TDCs are one of the most common (75%) asymptomatic mid-ine congenital neck masses in childhood.1–3 Persistent TDCs occurarely (7%) in adults.1,3,4 Amongst all cancers, thyroid carcinoma iselatively uncommon (2%).5 Reported cases of thyroid carcinomasccurring in TDC are extremely uncommon (1–2%).1–3,6,7

Though described in 1911 by Brentano, the first reported casen the English literature of a primary TPC in a TDC is by Owennd Ingelby in 1927.1,3,7 Controversies exist even today regarding:a) exact origin and (b) optimal management for incidental TPC inDC.1–3,7–9

Majority of TPCs in TDCs are discovered as an incidental find-ng on pathological examination of the excised cyst specimenreated by Sistrunk’s procedure based on the embryological devel-pment of the thyroid gland.9–13 Simple local excision of TDC is noonger advised due to recurrences related to incomplete removalf the thyroglossal tract.1,9 The rare discovery of an incidentalPC in a TDC raises questions regarding best practice guidelinesor further management which still remains controversial and

ebatable.1,9,13,14

We report the case of an incidental primary intraluminal well-ifferentiated TPC arising in a TDC and discuss the potential roles for

∗ Corresponding author at: 4681 Maple Grove Rd, Beamsville, ON, Canada.el.: +1 905 683 0469; fax: +1 905 562 0914.

E-mail addresses: [email protected] (M. Tharmabala),[email protected] (R. Kanthan).

210-2612/$ – see front matter © 2012 Surgical Associates Ltd. Published by Elsevier Ltdttp://dx.doi.org/10.1016/j.ijscr.2012.10.003

012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

total thyroidectomy, regional lymph-node dissection, radioactiveiodine, and suppressive thyroxine therapy as adjuvant therapy inthe context of relevant evidence-based literature.

2. Presentation of case

2.1. Case report

A 32-year-old female who presented with a painless 3 cmswelling in the anterior aspect of the neck, clinically compatiblewith a TDC was treated by a standard Sistrunk’s procedure.

Histopathological examination showed the presence of 0.8 cmpapillary neoplasm arising from the cyst wall which containedentrapped thyroid follicles in keeping with a TDC (Fig. 1a).Microscopic examination of the papillary neoplasm showed thepresence of complex fibrovascular cores lined by epithelium withcharacteristic nuclear features of well-differentiated low gradeTPC (Fig. 1b). No additional histological subtypes were identified.Immunohistochemical staining with antibodies to low molecularweight keratin, thyroid transcription factor-1 (TTF-1), and thy-roglobulin were strongly positive both in the papillary neoplasmand the residual trapped non-neoplastic thyroid follicles (Fig. 1c).The TPC arising in the TDC was completely excised with no evi-

dence of invasion of the underlying cyst wall. No further surgicaltreatment was undertaken as this was considered an incidentalwell-differentiated classical thyroid papillary microcarcinoma.1-year follow up was unremarkable.

. All rights reserved.

Page 2: Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

CASE REPORT – OPEN ACCESSM. Tharmabala, R. Kanthan / International Journal of Surgery Case Reports 4 (2013) 58– 61 59

Fig. 1. (a–c) Photomicrographs of TPC arising in the wall of the TDC. (a) Haematoxylin and eosin stained slides at low magnification (lens objective 2×) show the presence ofa papillary neoplasm arising from the cyst wall which contained entrapped thyroid follicles (black arrow→) in keeping with a thyroglossal duct cyst. (b) Haematoxylin andeosin stained slides at high magnification (lens objective 10×) confirms the presence of papillae with complex fibrovascular cores lined by the typical nuclei (ground glassn cinoms TF-1, aa

2

atdc

3

dcrdpwcrratti

ai

cmTH

itecot

nioc(mntn

uclei with grooves and pseudo-inclusions [black arrow→]) of thyroid papillary carhows strong positive staining with antibodies to low molecular weight keratin, Tdjacent papillary neoplasm.

.2. Review of Management Dilemmas of TPC in TDC

A Literature search using PubMed, Medline, Scopus, Embase,nd Google/Google Scholar limited to the English language usinghe search terms ‘thyroid papillary carcinoma’ AND ‘thyroglossaluct cyst’ AND thyroglossal duct remnants’ AND ‘management’ wasonducted.

. Discussion

The thyroid gland is one of the earliest endocrine glands toevelop in the human embryo.10 It descends from the foramenecum at the base of the tongue to the front of the neck in closeelation to the hyoid bone via the thyroglossal duct. Thyroglossaluct remnants, most commonly a cyst, develops due to incom-lete atrophy of the duct which usually occurs by the 7th foetaleek of gestation.13 TDC is the most common non-odontogenic

yst that presents as a neck mass at any point along the tract rep-esenting more than 75% of childhood midline neck masses. It isare in the adult population (7%).1,2,4,7,15 TDC clinically presentss a soft/firm/hard/fluctuant mass, that is generally movable inhe midline of the neck. TDCs occur along the thyroglossal tract:hyrohyoidal (61%), suprahyoidal (24%), suprasternal (13%), andntra-lingual region (2%).1

The development of malignancy in TDC is uncommon andpproximately 200 cases are reported in the English literature sincets first description in 1911.1,3,6,13

In up to two-thirds of TDCs, thyroid follicles that persist in theyst wall can rarely undergo neoplastic transformation.3 TPC is theost common histological type of (80%) malignancy that occurs in

DCs. Infrequently squamous, follicular, mixed papillary/follicular,ürthle cell and anaplastic carcinoma have been reported.1,2

The exact origin of TPC in a TDC is still debated as to whethert represents a ‘metastatic lesion’ from an occult primary TPC inhe thyroid gland versus its ‘de novo origin’.1,2,7,8,12,14 The pres-nce of entrapped thyroid follicles in the cyst wall, as seen in ourase (Fig. 1a), and the persistent absence of medullary carcinomaccurring in a TDC in keeping with its embryology, strongly favourshe ‘de novo theory’.1,2,16

The diagnosis of a carcinoma in a TDC is usually incidental witho additional clues to suspect this preoperatively at the initial clin-

cal presentation.1 The diagnosis of primary TPC in a TDC is onef exclusion using the Widstrom criteria which include: (1) car-inoma should be in the wall of the thyroglossal duct remnant,2) carcinoma must be differentiated from a cystic lymph node

etastasis by histological demonstration of a squamous or colum-ar epithelium lining and normal thyroid follicles in the wall ofhe thyroglossal duct remnant, and (3) there should be no malig-ancy in the thyroid gland or any other possible primary site.1,7

a. (c) Immunohistochemical stained slides at low magnification (lens objective 2×)nd thyroglobulin in the residual trapped thyroid follicles in the cyst wall and the

This latter criterion is highly debated as 11–45% of all thyroglos-sal duct remnant carcinoma cases have a synchronous thyroidcarcinoma.1,3

Pre-operative thyroid scan, ultrasound guided fine needle aspi-ration cytology (US-FNAC) and CT/MRI imaging of the neck aregaining more popularity to enhance the accuracy of preoperativediagnosis.2,17 Although, preoperative thyroid scans confirm thepresence of ectopic thyroid tissue in 33% of TDCs, such scans havenot been beneficial in the preoperative diagnoses of carcinoma inTDCs.9 US-FNAC though simple, rapid, inexpensive with minimalrisk complications is more reliable in diagnosing solid tumoursrather than cystic lesions. Additionally, FNAC is not cost-effectivedue to the rarity of this malignancy and remains an inappropri-ate tool for routine use in children.1,2,18 CT/MRI imaging of theneck are rarely indicated preoperatively unless there is a high clini-cal/FNAC suspicion of malignancy.1,2,7,17 Imaging features such as asolid nodule with calcification/irregular margin/thick wall are sug-gestive of malignancy.2,7 Ogawa et al. have suggested a possibleutilization of three-dimensional computed tomography in provid-ing accurate pre-operative diagnosis of TPC in a TDC.19

The dilemma involved with the further management of thediscovery of incidental TPC arising in a TDC, is largely relatedto whether additional management protocols such as total thy-roidectomy, regional lymph node dissection, radioactive iodine,and suppressive thyroxine therapy are warranted; as involvementof the thyroid gland has been reported in up to 11–45% of caseswherein a completion thyroidectomy was performed.1,12 Suchfindings also raise the possibility of the presence of multifocal dis-ease arising from synchronous TPC in the TDC and the native thyroidgland.1,3,20

In Patel et al’s analysis of 57 cases of well-differentiated car-cinomas in TDC, the only significant predictor for overall survivalwas the completeness of excision of TDC.8 Patients treated withsimple excision (10-yr survival 75%) had a worse prognosis thanthose with Sistrunk’s procedure (100%).1 It is hard to justify totalthyroidectomy as the overall cure rate of a carcinoma arising in aTDC treated by Sistrunk’s procedure is over 95%.9

Recently, prognostic risk group assessments are used toidentify patients who would benefit from additional totalthyroidectomy.1,2,7,8 Plaza et al. identified high risk factors: (a)age >45 years, (b) past radiation exposure, (c) presence of tumourin the thyroid gland on radiological evaluation, (d) presence ofclinical/radiological nodes, (e) tumour >1.5 cm in diameter, (f)cyst-wall invasion, and (g) positive margins on histopathologicalexamination as indicators for additional total thyroidectomy with

radioiodine and suppressive hormone therapy.1 Additional factorsthat guide therapy/risk assessment include gender, and tumourcharacteristics such as histological grade/type, tumour focality, andlymphovascular invasion.21
Page 3: Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

CASE REPORT – OPEN ACCESS60 M. Tharmabala, R. Kanthan / International Journal of Surgery Case Reports 4 (2013) 58– 61

l TPC i

7tatrit

otosAopdr

torr

4

bttham

M

D

Fig. 2. Proposed recommendations for the management of incidenta

Regional lymph node metastases have been reported in up to–15%. When nodal metastases are detected preoperatively, totalhyroidectomy and regional neck dissection are recommended inddition to Sistrunk’s procedure.1 Prophylactic lateral neck dissec-ion in the absence of detectable nodal metastases is not routinelyecommended.1,2,6,8 In selected cases, therapeutic nodal dissections limited to central compartment neck dissection in keeping withhese midline tumours.6

Suppressive hormone therapy and radioactive iodine are rec-mmended in all post-total thyroidectomy patients. In patientsreated by Sistrunk’s procedure alone suppression therapy is rec-mmended to suppress the thyroid tissue and to keep the thyroidtimulating hormone (TSH) levels between 0.1 and 0.5 mIU/L.nnual TSH levels and ultrasound scans of the neck are rec-mmended in the follow-up management protocols for theseatients.1 Proposed recommendations for the management of inci-ental TPC in TDC based on stratification of low, moderate, and highisk groups are presented in Fig. 2.

Papillary cancer is known to have a prolonged clinical courseherefore long term follow up (>20 years) is recommended.3 Theverall prognosis for TPC arising in a TDC is excellent with (a)eported 10-year survival rates of 95.6% and (b) distant metastaticate of <2%.8,16

. Conclusions

Primary TPC in adult TDCs is uncommon with the majorityeing diagnosed post-operatively as an incidental finding on defini-ive histopathological examination. The long-term management ofhese patients is based on their stratification of low, moderate, andigh risk groups. Though the overall prognosis for Incidental TPCrising in TDC is excellent, long term clinical follow up is recom-ended due to the prolonged natural clinical course of TPC.

edical disclaimer

This manuscript reflects the opinions and views of the authors,r. Mehala Tharmabala and Dr. Rani Kanthan and do not reflect any

[

n TDC based on stratification of low, moderate, and high risk groups.

official policy or medical opinion of the institutions with which theauthors are affiliated.

This manuscript has not been submitted elsewhere for publica-tion.

This manuscript has no relevant identification of personal dataand remains completely de-identified and is therefore exempt fromthe University of Saskatchewan Biomedical Ethics approval as perinstitutional policy.

Conflict of interest statement

The authors, Dr. Mehala Tharmabala and Dr. Rani Kanthan, donot have any financial, real or perceived conflict of interest in thepublication of this manuscript.

Funding

None.

Consent

Written informed consent was obtained from the patient atsurgery for research and publication of all surgical material.

A copy of the written consent is available for review by theEditor-in-Chief of this journal on request.

Author contributions

Dr. Tharmabala is a post graduate medical student who is thefirst author and has been responsible for the data collection, liter-ature review and preliminary draft writing of this manuscript.

Dr. Rani Kanthan is the Clinical Professor in charge of the casewith supervision of Dr. Tharmabala and overseeing the writing ofthis manuscript.

References

1]. Plaza CPR, Lopez MED, Carrasco CEG, Meseguer LM, Perucho AF. Managementof well-differentiated thyroglossal remnant thyroid carcinoma: time to close

Page 4: Incidental thyroid papillary carcinoma in a thyroglossal duct cyst – management dilemmas

– Oal Jour

[

[

[

[

[

[

[

[

[1

[1

[1

[1

[1

[1

[1

[1

[1

[1

[2

[2

OTpc

CASE REPORTM. Tharmabala, R. Kanthan / Internation

the debate? Report of five new cases and proposal of definitive algorithm fortreatment. Annals of Surgical Oncology 2006;13(5):745–52.

2]. Kermani W, Belcadhi M, Abdelkefi M, Bouzouita K. Papillary carcinoma arising ina thyroglossal duct cyst: case report and discussion of management modalities.European Archives of Oto-Rhino-Laryngology 2008;265:233–6.

3]. Dan D, Rambally R, Naraynsingh V, Maharaj R, Seetharaman H. A Case of malig-nancy in a thyroglossal duct cyst-recommendations for Management. Journal ofthe National Medical Association 2012;104(3–4):211–4.

4]. Hilger AW, Thompson SD, Smallman LA, Watkinson JC. Papillary carcinoma aris-ing in a thyroglossal duct cyst: a case report and literature review. The Journalof Layrngology and Otology 1995;109:1124–7.

5]. Eng TY, Litchke S, Diaz AZ, Luh JY. The management of metastatic thyroid car-cinoma: an initial presentation with bony metastasis. Journal of Cancer Therapy2011;2:503–6.

6]. Hartl DM, Ghuzlan AA, Chami L, Leboulleux S, Schlumberger M, Travagli JP.High rate of multifocality and occult lymph node metastases in papillary thy-roid carcinoma arising in thyroglossal duct cyst. Annals of Surgical Oncology2009;16:2595–601.

7]. Motamed M, McGlashan JA. Thyroglossal duct carcinoma. Current Opinions inOtolaryngology Head and Neck Surgery 2004;12:106–9.

8]. Patel SG, Escrig M, Shaha AR, Singh B, Shah JP. Management of well-differentiated thyroid carcinoma presenting within a thyroglossal duct cyst.Journal of Surgical Oncology 2002;79:134–9.

9]. LaRouere MJ, Drake AF, Baker SR, Righter HJ, Magielski JE. Evaluation and man-agement of a carcinoma arising in a thyroglossal duct cyst. American Journal of

Otolaryngology 1987;8:351–5.

0]. Sistrunk WE. The surgical treatment of cyst of the thyroglossal tract. Annals ofSurgery 1920;71:121–2.

1]. Ellis PD, Van Nostrand AWP. The applied anatomy of thyroglossal tract remnants.Laryngoscope 1977;87:765–70.

pen Accesshis article is published Open Access at sciencedirect.com. It is distribermits unrestricted non commercial use, distribution, and reproductredited.

PEN ACCESSnal of Surgery Case Reports 4 (2013) 58– 61 61

2]. Pribitkin EA, Friedman O. Papillary carcinoma in a thyroglossal duct remnant.Archives of Otolaryngology – Head and Neck Surgery 2002;128:461–2.

3]. Sun Z, Guo C, Yu G, Yi Z, Chen Y, Gao Y. Diagnosis and treatment of thyroglossalduct carcinoma: Report of three cases with review of literatures. Frontiers inMedicine of China 2008;2(1):58–62.

4]. O’Connel M, Grixti M, Harmer C. Thyroglossal duct carcinoma: presentationand management. Including eight case reports. Clinical Oncology 1998;10:186–90.

5]. Albayrak Y, Albayrak F, Kaya Z, Kabalar E, Aylu B. A case of papillary carci-noma in a thyroglossal cyst without a carcinoma in the thyroid gland. DiagnosticCytopathology 2010;39(1):38–41.

6]. Kennedy TL, Whitaker M, Wadih G. Thyroglossal duct carcinoma: a rationalapproach to management. The Laryngoscope 1998;108:1154–8.

7]. Torcivia A, Polliand C, Ziol M, Dufour F, Champault G, Barrat C. Papillary car-cinoma of the thyroglossal duct cyst: report of two cases. Romanian Journal ofMorphology and Embryology 2010;519(4):775–7.

8]. Yang YJ, Haghir S, Wanamaker JR, Powers CNP. Diagnosis of papillary carcinomain a thyroglossal duct cyst by fine needle aspiration biopsy. Archives of Pathologyand Laboratory Medicine 2000;124:139–42.

9]. Ogawa C, Kammori M, Onose H, et al. Utilization of three-dimensional com-puted tomography for papillary thyroid carcinoma arising in the thyroglossalduct remnant: report of a case. Surgery Today 2010;40:650–3.

0]. Roses DF, Snively SL, Phelps RG, Cohen N, Blum M. Carcinoma of the thyroglossalduct. The American Journal of Surgery 1983;145:266–9.

1]. Ghossein R, Asa SL, Barnes L, et al. Protocols for the examination of speci-mens from patients with carcinomas of the thyroid gland. Head and NeckThyroid Gland College of American Pathologist. http://www.cap.org/apps/docs/committees/cancer/cancer protocols/2011/Thyroid 11protocol.pdf [retrieved6.12.11].

uted under the IJSCR Supplemental terms and conditions, whichion in any medium, provided the original authors and source are


Recommended