Advertisment CMED
Home Print this page Email this page Users Online: 224
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 6  |  Issue : 1  |  Page : 15-20

Anatomic distribution and histologic subtypes of primary gastrointestinal lymphomas: A retrospective analysis of 152 cases


1 Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
2 Division of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
3 Division of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Web Publication29-Jun-2017

Correspondence Address:
Rekha A Nair
Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ccij.ccij_174_16

Rights and Permissions
  Abstract 

Background: Gastrointestinal (GI) lymphomas are a heterogeneous group of neoplasms. Studies have demonstrated a wide variation in the sites of involvement and histologic subtypes, which are independent prognostic factors. Hence, it is important to study the frequency and distribution pattern of GI lymphoma in a particular region. Aim: The aim of this study was to study all cases of primary GI lymphomas presented to our center for 5 years with reference to the pattern of distribution and histologic subtypes and compare our data with the literature. Materials and Methods: In this retrospective study, all cases of primary GI lymphomas over a period of 5 years from 2010 to 2014 were analyzed. Results: There were 152 cases of primary GI lymphomas. Age ranged from 3 years to 83 years. There were 133 adult patients and 19 pediatric patients. Most common site of involvement was small intestine followed by stomach, large intestine, and esophagus. Most common histologic subtype was diffuse large B-cell lymphoma (DLBCL), followed by Burkitt lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, follicular lymphoma, mantle cell lymphoma, B-cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma, and plasmablastic lymphoma. There were five cases of T-cell non-Hodgkin lymphoma which included adult T-cell leukemia/lymphoma, anaplastic large-cell lymphoma, enteropathy-associated T-cell lymphoma, and T-lymphoblastic lymphoma. One case of Hodgkin lymphoma with predominant involvement of the large intestine and without any peripheral node involvement was also encountered. Conclusion: In our series, the most common site of involvement was the small intestine. This is in contrast to majority of studies where the most common site is the stomach. Similar to the other studies, DLBCL was the most common histologic subtype. Compared to other studies, there were more number of Burkitt lymphoma and lesser number of MALT lymphoma in our series.

Keywords: Anatomic distribution, Burkitt lymphoma, diffuse large B-cell lymphoma, histologic subtypes, primary gastrointestinal lymphomas


How to cite this article:
Sukumaran R, Nair RA, Jacob PM, Vasudevan JA, Narayanan G, Kumary T P. Anatomic distribution and histologic subtypes of primary gastrointestinal lymphomas: A retrospective analysis of 152 cases. Clin Cancer Investig J 2017;6:15-20

How to cite this URL:
Sukumaran R, Nair RA, Jacob PM, Vasudevan JA, Narayanan G, Kumary T P. Anatomic distribution and histologic subtypes of primary gastrointestinal lymphomas: A retrospective analysis of 152 cases. Clin Cancer Investig J [serial online] 2017 [cited 2017 Aug 19];6:15-20. Available from: http://www.ccij-online.org/text.asp?2017/6/1/15/209151


  Introduction Top


The gastrointestinal tract (GIT) is the most common extranodal site involved by lymphoma.[1] Gastrointestinal (GI) lymphomas represent 1%–10% of all GI malignancies.[2] The incidence of GI lymphomas has been increasing worldwide. Primary GI lymphomas can occur in any part of the GIT. In majority of studies, stomach is the commonly affected site followed by small intestine.[3],[4] Majority of GI lymphomas are non-Hodgkin lymphomas (NHLs) of B-cell origin. The most common histologic types are diffuse-large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma.[5] Few cases of T-cell lymphomas are also reported. The occurrence of Hodgkin lymphoma is extremely rare in GIT. The distribution pattern of GI lymphomas varies in different geographical regions.


  Materials and Methods Top


In this retrospective study, all the cases of primary GI lymphomas diagnosed over a period of 5 years from January 2010 to December 2014 were analyzed. Nodal lymphomas with secondary involvement of the GIT and recurrence of previously diagnosed and treated GI lymphomas were excluded from the study. The age and sex of the patients, sites of involvement, and histologic subtypes of lymphomas were noted. The diagnosis was based on the morphological findings on hematoxylin and eosin-stained sections and the immunohistochemical profiles. The immunohistochemical markers used in the diagnosis and subtyping included CD45, CD20, CD79a, PAX5, CD10, CD3, CD5, CD7, CD4, CD8, CD30, BCL6, BCL2, CD38, SIgM, CD21, CD23, cyclin D1, CD138, kappa, lambda, CD34, Tdt, CD15, anaplastic lymphoma kinase (ALK), epithelial membrane antigen, cytokeratin, synaptophysin, chromogranin, and MIB-1. The subtype classification was done according to the 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.[1]


  Results Top


During the study period of 5 years (from January 2010 to December 2014), 152 cases were diagnosed as primary GI lymphomas. Twenty-four were in-house cases and 128 were referral cases from outside hospitals.

Age of the patients ranged from 3 years to 83 years and the median age was 50 years. Nineteen were pediatric patients and 133 were adults. There were 107 male patients and 45 females with a male:female of 2.4:1.

Most common site of involvement was the small intestine. There were 68 cases of small intestinal lymphomas which accounted for 44.74% of the total cases. This was followed by gastric lymphoma with 36 cases (23.68%). There were 32 cases (21.05%) of large intestinal lymphomas, 13 cases (8.55%) of ileocecal lymphomas, and 3 cases (1.97%) of esophageal lymphomas [Table 1].
Table 1: Site distribution and histological subtypes of gastrointestinal lymphoma

Click here to view


DLBCL was the most common histologic variant. There were 82 cases of DLBCL (53.95% of total cases). In all the anatomical sites, DLBCL was the predominating subtype [Table 1].

There were 29 cases (19.08% of total cases) of Burkitt lymphoma. Of these 29 cases, 21 cases occurred in the ileum and ileocecal region. Seventeen cases were in the age group of 3–10 years with a striking male predominance (15 male and 2 female patients).

There were 17 cases of MALT lymphoma which formed 11.18% of the total cases. Predominant site of involvement was the stomach followed by small intestine, large intestine, and ileocecal region.

Of the nine cases of follicular lymphoma, seven cases occurred in the small intestine. One case each involved the large intestine and the ileocecal region. Majority of the cases (six cases) were Grade 3 follicular lymphomas.

Four cases of primary mantle cell lymphomas including two cases of blastoid mantle cell lymphomas were reported. Two cases involved the large intestine, one case each in the small intestine and in the stomach.

Three cases were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma. All the three cases were in the small intestine.

There were two cases of plasmablastic lymphoma, one in the esophagus and one in the small intestine.

Five cases of T-cell lymphomas were encountered which constituted 3.29% of the cases and included adult T-cell leukemia/lymphoma (ATLL) (two cases), anaplastic large cell lymphoma (ALCL) (one case), enteropathy-associated T-cell lymphoma (EATL) (one case), and T-lymphoblastic lymphoma (one case).

There was one case of primary Hodgkin lymphoma involving the large intestine with the main bulk of disease in the large intestine with minimal involvement in the pericolic nodes and no evidence of other nodal involvement.

During the study, we encountered three cases with synchronous occurrence of lymphomas and nonlymphoid malignancies. This included one case of MALT lymphoma and adenocarcinoma of stomach, one case of DLBCL of stomach and neuroendocrine tumor of duodenum, and another case of DLBCL of intestine and nonsmall cell carcinoma of lung.


  Discussion Top


Gastrointestinal lymphomas are a heterogeneous group of neoplasms and constitute 10%–15% of all NHLs.[6] In 1961, Dawson et al. defined primary GI lymphomas as a tumor that predominantly involves the GIT with lymph node involvement confined to the drainage area of the primary tumor site. According to these authors, there should not be any palpable lymph nodes or involvement of liver or spleen. There should be normal chest radiograph and normal peripheral white cells.[7] Later, in 1978, Lewin et al. defined primary GI lymphomas as those in which the involvement of alimentary tract predominates or those with symptoms of GIT involvement on presentation.[8]

The amount and nature of lymphoid tissue vary in different parts of intestine. The risk factors involved in the development of GI lymphoma include Helicobacter pylori infection, human immunodeficiency virus, Campylobacter jejuni, Epstein–Barr virus, hepatitis B virus, human T-cell lymphotropic virus-1 (HTLV-1), celiac disease, inflammatory bowel disease, and immunosuppression.[9],[10]

The histological subtypes of GI lymphomas vary according to the normal lymphoid distribution and according to the etiological factors. Clinically, GI lymphomas are indistinguishable from other benign and malignant conditions. Hence, biopsy is essential for a definite diagnosis. On histopathologic examination, low-grade lymphomas should be differentiated from reactive lymphoid infiltrates and high-grade lymphomas from nonlymphoid malignancies. Certain histological subtypes have been noted to have a relative predilection site. For example, MALT lymphoma occurs more commonly in stomach, mantle cell lymphoma in terminal ileum, jejunum, and colon, EATL in jejunum, and follicular lymphoma in duodenum.[11]

Distribution pattern

Primary lymphomas are very rare in the esophagus and constitute <1% of all GI lymphomas. Endoscopic findings of ulcers, plaques, polypoidal or circumferential lesions can mimic carcinoma. Histopathologic examination is essential in making the diagnosis. Esophageal lymphomas usually occur as a result of secondary involvement from cervical or mediastinal lymph nodes or direct extension from gastric lymphoma. Nonlymphoid malignancy and secondary involvement of lymphomas should be excluded before making a diagnosis of primary esophageal lymphoma.[12],[13],[14] In our series, there were three cases (1.97%) of primary esophageal lymphomas, two cases of DLBCL, and one case of plasmablastic lymphoma.

Literature search shows stomach as the most frequent site of involvement of GI lymphomas in majority of studies ranging from 38.5% to 75% [Table 2].[15],[16],[17],[18] In stomach, B-lymphocytes and plasma cells are absent and a few CD8 positive T-cells can be seen in intraepithelial locations and CD4 positive T-cells in the lamina propria. Reactive lymphoid follicles are seen in chronic gastritis. Chronic gastritis associated with H. pylori infection is a precursor for the development of MALT lymphoma.[12],[14] Lymphoepithelial lesions, dense ill-defined infiltrate of monotonous B-cells extending away from lymphoid follicles, and cytological atypia favor a neoplastic process. In our series, stomach was the second most common site of involvement. There were 36 cases of primary gastric lymphomas which constituted 23.6% of all GI lymphomas. In contrast to majority of studies where MALT lymphoma is the most common subtype of gastric lymphoma, DLBCL was the predominant subtype in our study and constituted 21 cases (58.3% of all primary gastric lymphomas).[14],[15],[16],[17] There were eight cases of MALT lymphoma, four cases of Burkitt lymphoma, one case each of blastoid mantle cell lymphoma, ALCL, and T-lymphoblastic lymphoma.
Table 2: Site distribution of gastrointestinal lymphoma and comparison with literature

Click here to view


Small intestine was the most common site of involvement by primary GI lymphoma in our study. This is in contrast to the majority of published studies.[14],[15],[16],[17] In the intestine, there are large amount of lymphoid tissue in the mucosa and submucosa which contain both B- and T-cells and elicit adaptive immune response against the mucosal antigens.[12],[13],[14] In our study, the subtype distribution of small intestinal lymphomas was more diverse. In adults, DLBCL was the most common subtype whereas in children, Burkitt lymphoma was the predominant type. Others included follicular lymphoma, MALT lymphoma, B-cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma, EATL, mantle cell lymphoma, and plasmablastic lymphoma.

Ileocecal region was defined as the area from the terminal of ileum to the cecum. The ambiguity of anatomical classification of this site resulted in different frequencies of small intestinal and large intestinal lymphomas. In this study, 13 cases (8.55%) were in the ileocecal region. Majority were Burkitt lymphoma. Others included DLBCL, MALT lymphoma, follicular lymphoma, and ATLL.

Primary colorectal lymphomas account for 0.2%–0.6% of all large intestinal malignancies. Inflammatory bowel disease and immunosuppression are the risk factors for the development of primary colorectal lymphomas. In our series, there were 32 cases of colorectal lymphomas. DLBCL was the predominant subtype with twenty cases. The subtype distribution was diverse and included Burkitt lymphoma, MALT lymphoma, follicular lymphoma, mantle cell lymphoma including blastoid variant, ATLL, and Hodgkin lymphoma.

Histologic subtypes

DLBCL is the most common subtype of primary GI lymphoma in majority of the studies.[14],[15],[16],[17],[18],[19],[20],[21] In our study also, DLBCL was the most common histological subtype and accounted for 53.95% of total cases [Table 3]. In all the anatomical sites, DLBCL was the most common subtype. DLBCL with signet ring-like morphology and CD5 positive DLBCL were encountered in the study period.
Table 3: Histological subtypes of gastrointestinal lymphoma and comparison with literature

Click here to view


In contrast to the majority of studies, our study showed increased number of Burkitt lymphoma cases.[14],[15],[16],[17] Common sites affected by Burkitt lymphoma were the small intestine and the ileocecal region. Majority of the cases occurred in the pediatric age group.

The incidence of MALT lymphoma was less compared to other studies. In cases where there was difficulty in distinguishing reactive lymphoid infiltrate and MALT lymphoma, features such as cellular atypia, lymphoepithelial lesions, and sheeting of B-cells with CD20 staining helped in arriving at definite diagnosis. The distinction between MALT lymphoma with extensive plasmacytic differentiation and plasmacytoma was challenging. Extensive search for the presence of a small lymphoid cell infiltrate along with CD20 positivity and absence of other parameters of myeloma helped in the differentiation.

Of the nine cases of follicular lymphoma, seven cases occurred in the small intestine. Six cases were Grade 3 follicular lymphomas.

We encountered four cases of mantle cell lymphoma which included two cases of blastoid variant. Common presentation of mantle cell lymphoma was as polypoidal masses. The use of CD5 in the first-line immunopanel helped in the identification of blastoid mantle cell lymphoma.

Three cases were diagnosed as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma. All the three cases occurred in the small intestine and showed a high MIB-1 labeling index.

Two cases were diagnosed as plasmablastic lymphoma. One case was in the esophagus and the other was in the small intestine. Both these cases occurred in immunocompetent people.

The occurrence of T-cell lymphomas is rare in the GIT.[22],[23] In our study, there were five cases of T-cell lymphomas which accounted for 3.29% of cases. It included ATLL, ALCL, EATL, and T-lymphoblastic lymphoma. There were two cases of ATLL, one case involving the ileocecum and the other involving the large intestine. The neoplastic cells showed positivity for CD3 and CD5 with downregulation of CD7. The cells were also positive for CD25. The diagnosis was confirmed by serum HTLV-1 estimation. One case of ALCL involving the stomach was encountered where the neoplastic cells were brightly positive for CD30 and ALK, weakly positive for CD45 and CD3, and were negative for B-cell markers. One case of EATL involving the ileum was encountered where the neoplastic cells were CD3 and CD7 positive and CD5 negative. There was one case of T-lymphoblastic lymphoma involving the stomach in an adult patient. The neoplastic cells were positive for CD3, CD5, and Tdt and were negative for CD34, CD10, CD20, CD33, MPO, and BCL6. Blood smear and bone marrow were within normal limits.

One case of classical Hodgkin lymphoma involving the large intestine without any evidence of peripheral node involvement was noted in the study period. Microscopy showed large mono- and bi-nucleate cells with prominent eosinophilic nucleoli in a polymorphous background of small lymphocytes, plasma cells, histiocytes, eosinophils, and neutrophils. The large atypical cells were CD20 negative, CD30 positive, PAX5 positive, and CD15 negative. Primary involvement of GIT is very rare in Hodgkin lymphoma. Secondary involvement should always be excluded by detailed clinical and radiological evaluation.

Synchronous cases of lymphoma and nonlymphoid malignancies are well described. There was one case of synchronous MALT lymphoma and adenocarcinoma of the stomach. Recently, there is a worldwide increased rate of detection of the cooccurrence of these two tumors. Various theories have been put forward to explain this occurrence. One theory is that one preexisting tumor provokes the other. Another theory is that the two tumors arise independently as a result of the same carcinogenic action.[24] It is suggested that H. pylori might play an important role in the development of both lymphoma and carcinoma. We had one synchronous case of DLBCL of the stomach and neuroendocrine tumor of the duodenum. Another case showed synchronous occurrence of DLBCL intestine and nonsmall cell lung cancer.


  Conclusion Top


This retrospective study from a single institution highlights the anatomic distribution and histologic subtypes of primary GI lymphoma in a southern state of India. In this study, DLBCL was the most common histologic subtype in all the anatomic sites. This finding is in concordance with other studies. The incidence of MALT lymphoma was low and there was a strikingly high incidence of Burkitt lymphoma. In contrast to other studies, small intestine was the most common site of involvement of GI lymphoma in our study. These findings highlight the geographic variation in the occurrence of GI lymphoma in our area.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pilleri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008.  Back to cited text no. 1
    
2.
Bellesi G, Alterini R, Messori A, Bosi A, Bernardi F, di Lollo S, et al. Combined surgery and chemotherapy for the treatment of primary gastrointestinal intermediate- or high-grade non-Hodgkin's lymphomas. Br J Cancer 1989;60:244-8.  Back to cited text no. 2
[PUBMED]    
3.
Wang GB, Xu GL, Luo GY, Shan HB, Li Y, Gao XY, et al. Primary intestinal non-Hodgkin's lymphoma: A clinicopathologic analysis of 81 patients. World J Gastroenterol 2011;17:4625-31.  Back to cited text no. 3
    
4.
Burke JS. Lymphoproliferative disorders of the gastrointestinal tract: A review and pragmatic guide to diagnosis. Arch Pathol Lab Med 2011;135:1283-97.  Back to cited text no. 4
    
5.
Howell JM, Auer-Grzesiak I, Zhang J, Andrews CN, Stewart D, Urbanski SJ. Increasing incidence rates, distribution and histological characteristics of primary gastrointestinal non-Hodgkin lymphoma in a North American population. Can J Gastroenterol 2012;26:452-6.  Back to cited text no. 5
    
6.
d'Amore F, Brincker H, Grønbaek K, Thorling K, Pedersen M, Jensen MK, et al. Non-Hodgkin's lymphoma of the gastrointestinal tract: A population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group. J Clin Oncol 1994;12:1673-84.  Back to cited text no. 6
    
7.
Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the intestinal tract. Report of 37 cases with a study of factors influencing prognosis. Br J Surg 1961;49:80-9.  Back to cited text no. 7
    
8.
Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the gastrointestinal tract: A study of 117 cases presenting with gastrointestinal disease. Cancer 1978;42:693-707.  Back to cited text no. 8
    
9.
Engels EA. Infectious agents as causes of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 2007;16:401-4.  Back to cited text no. 9
    
10.
Müller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin's lymphoma (NHL): Trends, geographic distribution, and etiology. Ann Hematol 2005;84:1-12.  Back to cited text no. 10
    
11.
Rizvi MA, Evens AM, Tallman MS, Nelson BP, Rosen ST. T-cell non-Hodgkin lymphoma. Blood 2006;107:1255-64.  Back to cited text no. 11
    
12.
Cardona DM, Layne A, Lagoo AS. Lymphomas of the gastro-intestinal tract – Pathophysiology, pathology, and differential diagnosis. Indian J Pathol Microbiol 2012;55:1-16.  Back to cited text no. 12
  [Full text]  
13.
Ghimire P, Wu GY, Zhu L. Primary gastrointestinal lymphoma. World J Gastroenterol 2011;17:697-707.  Back to cited text no. 13
    
14.
Arora N, Manipadam MT, Pulimood A, Ramakrishna BS, Chacko A, Kurian SS, et al. Gastrointestinal lymphomas: Pattern of distribution and histological subtypes: 10 years experience in a tertiary centre in South India. Indian J Pathol Microbiol 2011;54:712-9.  Back to cited text no. 14
[PUBMED]  [Full text]  
15.
Ding W, Zhao S, Wang J, Yang Q, Sun H, Yan J, et al. Gastrointestinal lymphoma in Southwest China: Subtype distribution of 1,010 cases using the WHO (2008) classification in a single institution. Acta Haematol 2016;135:21-8.  Back to cited text no. 15
    
16.
Shirsat HS, Vaiphei K. Primary gastrointestinal lymphomas – A study of 81 Cases from a Tertiary Healthcare Centre. Indian J Cancer 2014;51:290-2.  Back to cited text no. 16
[PUBMED]  [Full text]  
17.
Warrick J, Lou J, Robirds D, Branson J, Frater JL, Kreisel F, et al. Gastrointestinal lymphomas in a North American population: Clinicopathological features from one major Central–Midwestern United States tertiary care medical centre. Diagn Pathol 2012;7:76.  Back to cited text no. 17
    
18.
Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, et al. Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001;19:3861-73.  Back to cited text no. 18
    
19.
Bani-Hani KE, Yaghan RJ, Matalka II. Primary gastric lymphoma in Jordan with special emphasis on descriptive epidemiology. Leuk Lymphoma 2005;46:1337-43.  Back to cited text no. 19
    
20.
Sukpanichnant S, Udomsakdi-Auewarakul C, Ruchutrakool T, Leelakusolvong S, Boonpongmanee S, Chinswangwatanakul V. Gastrointestinal lymphoma in Thailand: A clinicopathologic analysis of 120 cases at Siriraj Hospital according to WHO classification. Southeast Asian J Trop Med Public Health 2004;35:966-76.  Back to cited text no. 20
    
21.
Ibrahim EM, Ezzat AA, Raja MA, Rahal MM, Ajarim DS, Mann B, et al. Primary gastric non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma. Ann Oncol 1999;10:1441-9.  Back to cited text no. 21
    
22.
Chott A, Dragosics B, Radaszkiewicz T. Peripheral T-cell lymphomas of the intestine. Am J Pathol 1992;141:1361-71.  Back to cited text no. 22
    
23.
Shet T, Karpate A, Bal M, Gupta S, Gujral S, Nair R. Primary intestinal T cell lymphomas in Indian patients – In search of enteropathic T cell lymphoma. Indian J Pathol Microbiol 2010;53:455-9.  Back to cited text no. 23
[PUBMED]  [Full text]  
24.
Lee SY, Kim JJ, Lee JH, Kim YH, Rhee PL, Paik SW, et al. Synchronous adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma in a single stomach. Jpn J Clin Oncol 2005;35:591-4.  Back to cited text no. 24
    



 
 
    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
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed110    
    Printed7    
    Emailed0    
    PDF Downloaded3    
    Comments [Add]    

Recommend this journal