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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 1  |  Page : 48-51
 

Evaluating the relation between patients-related factors and dissected lymph node ratio in gastric cancer


1 Assistant Professor of Radiation Oncology, Razi Hospital, Gilan University of Medical Sciences, Rasht, Iran
2 Department of Radiation Oncology, Faculty of Medicine, Cancer Research Center, Omid Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Gastroenterology and Hepatology, Gilan University of Medical Sciences, Rasht, Iran
4 Medical Student, Department of Radiation Oncology, Gilan University of Medical Sciences, Rasht, Iran

Date of Web Publication3-Feb-2016

Correspondence Address:
A Shafaghi
Department of Gastroenterology and Hepatology, Gilan University of Medical Sciences, Rasht
Iran
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Source of Support: This research was founded by Research Affairs at the Gilan University of Medical Sciences., Conflict of Interest: None


DOI: 10.4103/0019-509X.175559

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 » Abstract 

Background: Gastric cancer is a forth common malignancy world-wide and the second most common cause of cancer-related deaths. According to the current International Union Against Cancer staging system, nodal status is categorized based on the number of metastatic lymph nodes (LNs). Some groups have recently proposed the metastatic lymph node ratio (MLR) (the ratio between metastatic LNs and total dissected LNs; MLR) as an alternative prognostic factor. The aim of the present study is to evaluate the relationship between MLR and different clinico pathologic factors including patients' age, tumor grade, stage, sites of involvement and disease prognosis. Methods: Atotal of 70 patients with gastric adenocarcinoma who underwent gastrectomy with negative margin and LN resection during 2004-2009 and were referred to Radiotherapy-Oncology Department of Name of Hospital, Name of City, were included in the study. MLR status was divided to five groups. Collected data were analyzed with SPSS 16 (SPSS Inc., Chicago, IL, USA). Results: The difference between MLR groups in age was significant; older patients had lower MLR (P = 0.01). The ratio of male to female was 5.3, which indicated higher prevalence of gastric cancer in males. The difference between MLR groups for tumor location, tumor stage, disease free periods and tumor T stages were not significant. A significant relation existed between different stages of LN involvement and MLR; and also between cancer stages and MLR. Conclusion: We found a significant relation between MLR and cancer stage and metastatic LN. Due to small sample size and short period of follow-up, we could not find significant relation between MLR and other factors such as depth of tumor invasion, disease free period and tumor grading. In conclusion with regards to our results and other similar studies' results, we acknowledge the importance of MLR in determining patients' prognosis in gastric cancer.


Keywords: Breast cancer, dissected lymph nodes, metastatic lymph nodes


How to cite this article:
Saedi H S, Fanipakdel A, Shafaghi A, Ghorbani S. Evaluating the relation between patients-related factors and dissected lymph node ratio in gastric cancer. Indian J Cancer 2015;52:48-51

How to cite this URL:
Saedi H S, Fanipakdel A, Shafaghi A, Ghorbani S. Evaluating the relation between patients-related factors and dissected lymph node ratio in gastric cancer. Indian J Cancer [serial online] 2015 [cited 2019 Dec 7];52:48-51. Available from: http://www.indianjcancer.com/text.asp?2015/52/1/48/175559



 » Introduction Top


Gastric cancer, is a forth common malignancy world-wide (6.8% of all cancers) and the second most common cause of cancer-related deaths (10.4% of total cancer related deaths).[1] In some of the countries especially Fareast countries such as China, Japan and Korea, it is one of the most common cancer types leading to death.[2] In Iran, gastric cancer is the most common gastrointestinal malignancy and the most common cause of malignancy related deaths. Despite a decrease in its incidence in recent decades, the prognosis of gastric cancer is still poor.[3] The early signs and symptoms of gastric cancer are vague and unspecific therefore it is usually diagnosed in late stages. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement.[3] Many of the studies have evaluated the causes, prognostic factors and treatments for gastric cancer. In spite of recent advances in multimodality treatment and targeted therapy, complete resection is remained the only curative treatment modality.[4]

Lymph node (LN) metastasis is one of the most important prognostic factors of gastric cancer.[5],[6],[7] Even in early gastric cancer, the incidence of LN metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8-23.6% depending on cancer depth.[8] Studies have indicated that the depth of invasion and the presence or absence of LN metastasis is the most important prognostic factors in gastric cancer.[9],[10]

According to the current the International Union Against Cancer (UICC)/American Joint Committee on Cancer staging system, nodal status is categorized based on the number of metastatic LNs (pN0, no metastasis; pN1, 1-6 LNs positive; pN2, 7-15 and pN3, >15). Some groups have recently proposed the metastatic lymph node ratio (MLR) (the ratio between metastatic LNs and total dissected LNs; MLR) as an alternative prognostic factor to supplement the limitations of the conventional N staging system, particularly when a limited number of LNs is obtained.[2]

In this regard, early studies had shown that metastatic LN was one of the most critical prognostic factors in gastric carcinoma.[11],[12],[13] Since the UICC tumor node metastasis (TNM) classification for LN staging standard was modified in 1997, LN metastatic sites were replaced by the number of metastatic LN to evaluate the prognosis of patients. However, the number of dissected metastatic LN affected the accuracy of N staging, or even leaded to N staging bias.[14]

Recent studies as well confirmed the value of MLR as a prognostic factor in gastric cancer. Lee et al. in his published study in 2010 considering his results declared that the MLR was a simple and reproducible prognostic factor that supplemented the limitation of the conventional N staging system and provided more accurate prognostic stratification in advanced gastric cancer. In addition to patients' age, tumor size and chemotherapy, MLR was a strong prognostic factor for gastric cancer.[2] Feng et al. also conducted a study in 2011 about prognostic value of MLR and concluded that the metastatic LN ratio is an independent risk factor of the prognosis of T3 gastric cancer patients.[15]

The aim of the present study was to evaluate the relationship between MLR and different clinico-pathologic factors including patients' age, tumor grade, tumor stage, site of involvement and disease prognosis.


 » Methods Top


This was a cross-sectional descriptive study taking place during spring of 2004 to spring of 2009. All the patients with gastric adenocarcinoma who had gastrectomy with negative margin and LN resection during 2004-2009 and who was referred to Radiotherapy-Oncology Department of Name of Hospital, Name of City, were included in the study. Any other pathology except adenocarcinoma, patients who had gastrectomy with microscopic or macroscopic positive margin, patients with distance metastasis and those without LN resection were excluded from study. The patients were subjected to follow-up for at least 2 years.

The ratio of metastatic LN to total number of resected LN was divided into four groups: MLR 0 = 0, MLR 1 = 0-0.3, MLR 2 = 0.3-0.6 and MLR 3 = 0.6-1. Patients' health records were assessed and all the factors related to MLR including age, gender, tumor stage, grade and depth of involvement were extracted from it. Data were analyzed with SPSS 16 (SPSS Inc., Chicago, IL, USA). To compare the quantitative variables, mean and standard deviation and for qualitative variables, frequency tables and percent were used. ANOVA, Chi-square and post-hoc tests were used to analysis the data.


 » Results Top


A total of 70 patients with gastric adenocarcinoma were included in this study. The mean age of patients was 60.93 years with range of 25-85 years old. ANOVA and post-hoc tests determined a significant difference in patients' age between MLR groups; the mean age of patients with MLR 0.6-1, was less than the mean age of patients with MLR 0, which means older patients had lower MLR (P = 0.01). The majority of our patients were male (84%) and the ratio of male to female was 5.3, which indicated higher prevalence of gastric cancer in males. Patients' demographic information and disease free periods based on MLR groups as shown in [Table 1].
Table 1: Comparison of frequency of different MLRs based on age, gender and disease free period

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Chi-square test revealed no significant difference for gender between MLR groups (P = 0.23). The longest disease free period was 65 months and the shortest was 1 month. The mean of disease free period for patients in group MLR 0 and MLR 1 was similar (5 and 6 months). Since the distribution of data was not normal, the Kruskal-Wallis test was used to evaluate MLR groups for disease free periods, the difference between groups was not statistically significant (P = 0.01).

The relation between tumor location and MLR groups and also tumor stage and MLR groups with Chi-square test were not significant (P = 0.33 and P = 0.49 respectively). Forty patients did not have any LN metastasis, in most of patients (32) the LN involvement was less than five nodes (N1) and all the patients with more than 15 nodes involvement (N3) belonged to MLR groups 0.3-1. Chi-square test showed a statistically significant relation between the number of involved LNs and MLR (P = 0.001). In regard to tumor staging most of our patients (64%) were in T3 stage and the least were in T4 stage. The relation between tumor T stages and MLR was not significant. In the current study, most of the patients were in stage 2 (57%) and only 7% were in stage 1, which the entire last group had MLR of 0-0.3. The information about cancer location, its grading, T stage and Stage based on MLR groups as shown in [Table 2].
Table 2: Comparison of frequency of different MLRs based on tumor location, grade, T stage and N stage

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The Chi-square test detected statistically significant relation between cancer stages and MLR groups (P < 0.001), which means when malignancy progresses, MLR tends to increases, as well. Nearly 25% of patients (18) had relapse which seven of them had MLR < 0.3 and 11 had MLR between 0.3-1. There was no significant difference between patients with MLR < 0.3 and patients with MLR = 0.3-1 in relapse rate (P = 0.41). We also did not find any significant relation between gender and MLR. A significant relation existed between different stages of LN involvement and MLR; MLR increase as the number of involved LN increase (Chi-square test). The relation between cancer stages and MLR is also significant; as the cancer progresses, the MLR increases.


 » Discussion Top


Gastric adenocarcinoma is one of the main causes of death from cancer in the world and has the second place after lung cancer. More than 50% of patients with gastric cancer have LN metastasis, which leads to weak prognosis. Metastasis to LNs is considered the main prognostic factor for gastric cancer patients who undergo radical resection.[4]

In 1997, the UICC proposed that the category of LN involvement should be classified according to the number of metastatic LNs. It has been reported that the category based on the number of metastatic LNs is more sensitive than that based on the location of metastatic LNs in prognostic evaluation of gastric cancer.[16],[17],[18]

Studies demonstrated that the MLR was a simple and reproducible prognostic factor that supplemented the limitation of the conventional N staging system and provided more accurate prognostic stratification in advanced gastric cancer.[2],[4],[15] Kwon et al. in his study showed that MLR is one of the main factors in predicting 5 years survivals of patients with gastric cancer. Besides the MRL is more valuable and reliable prognostic factor than total metastatic LN because in fact it remove the effects of total number of resected LNs in determining patient prognosis.[19]

In this study, we evaluated 70 patients with gastric adenocarcinoma. Patients with distance metastasis and those with positive microscopic (R1) or macroscopic (R2) margins were excluded from the study. Most of our patients were males (59) and 11 were female; the ratio of male to female was 5.3. In most of other studies, this ratio is less [2],[4],[20],[21] which could be because of difference in demographic and cultural factors. In our study, population oldest patient was 85-years-old and the youngest was <25-year-old, the mean age of patients was 60.93.

In Shanghai study the oldest patient was 82-year-old and the youngest was 29 with the mean of 64 years.[21] Age and gender distribution of patients in this study was similar to most of other studies. Regarding the depth of invasion we divided the patients into four groups; T1: Tumor invasion to Lamina propria (three patients), T2: Tumor invasion to propria muscularis (20 patients), T3: Tumor invasion to serosa (45 patients) and T4: Tumor invasion to adjacent tissues (two patients). In Ding et al. study patients were divided to three groups mucosal and sub-mucosal (21 patients), muscular and sub muscular (22 patients) and serosa [22] (126).

The total number of resected LNs was 1240 (2-40) and the total of resected LN with metastasis was 382 (0-35). We found significant difference between MLR groups for age; the mean age of patients with MLR 0.6-1 was significantly lower than the mean age of patients with MLR 0, on the other hand younger patients had higher MLR compared with older (P = 0.01) and therefore worse prognosis, which is not similar to other studies. This dissimilarity may be the result of difference in our socio-cultural context.

We also found statistically significant relation between MLR and number of metastatic LNs; as the number of involved LNs increase, MLR increase as well (P < 0.001). This result is comparable with Lutfi study in Istanbul, Turkey.[23] Our results demonstrated that a statistically significant difference existed between MLR and stages of disease which with disease progress the MLR increase (P < 0.001), this is similar to other studies results.[2],[11],[12],[13],[23] We did not find significant relation between MLR and patients' gender, the depth of tumor invasion, the disease free period, tumor location and relapse. However, some of other studies have found a strong significant relation between MLR and patients survival; as the MLR increases, patient survival decreases. This difference between results may be the consequence of our small study population and short follow-up duration.

As the most important prognostic factors in patients with gastric cancer are stage of disease and the amount of LN involvement, we found the significant relation between MLR and cancer stage and metastatic LN. Our results indirectly indicated the correlation between MLR and some variables in patients with gastric cancer. Due to small sample size and short period of follow-up, we could not find relation between MLR and other factors like depth of tumor invasion, disease free period and tumor grading. In Lutfi study the ratio of involved LNs was significantly higher in patients with large tumors, invasion to blood vessels, lymphatic invasion or neural invasion and also tumor depth.[23] It has been shown that MLR has direct relation with invasion to lymphatic vessels and depth of tumor invasion.[21] It was also related with tumor size and depth of submocusal invasion.[22]


 » Conclusion Top


Considering the value of MLR in determining patient prognosis we recommend multi-centeric and multi-stage studies with larger sample size and longer follow-up duration to reach more reliable results. However in conclusion, although we did not find any significant relation between gender and MLR and stages of MRL, but it seems there is correlation between different stages of LN involvement and MLR; and also between cancer stages and MLR.

 
 » References Top

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2.
Lee SY, Hwang I, Park YS, Gardner J, Ro JY. Metastatic lymph node ratio in advanced gastric carcinoma: A better prognostic factor than number of metastatic lymph nodes? Int J Oncol 2010;36:1461-7.  Back to cited text no. 2
    
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Forman D, Burley VJ. Gastric cancer: Global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol 2006;20:633-49.  Back to cited text no. 3
    
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Huang CM, Lin JX, Zheng CH, Li P, Xie JW, Lin BJ, et al. Prognostic impact of metastatic lymph node ratio on gastric cancer after curative distal gastrectomy. World J Gastroenterol 2010;16:2055-60.  Back to cited text no. 4
    
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Wu CW, Hsieh MC, Lo SS, Tsay SH, Lui WY, P'eng FK. Relation of number of positive lymph nodes to the prognosis of patients with primary gastric adenocarcinoma. Gut 1996;38:525-7.  Back to cited text no. 5
    
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Li C, Kim S, Lai JF, Oh SJ, Hyung WJ, Choi WH, et al. Solitary lymph node metastasis in gastric cancer. J Gastrointest Surg 2008;12:550-4.  Back to cited text no. 6
    
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Mishima Y, Hirayama R. The role of lymph node surgery in gastric cancer. World J Surg 1987;11:406-11.  Back to cited text no. 7
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Roviello F, Rossi S, Marrelli D, Pedrazzani C, Corso G, Vindigni C, et al. Number of lymph node metastases and its prognostic significance in early gastric cancer: A multicenter Italian study. J Surg Oncol 2006;94:275-80.  Back to cited text no. 8
    
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Adachi Y, Mori M, Maehara Y, Sugimachi K. Dukes's classification: A valid prognostic indicator for gastric cancer. Gut 1994;35:1368-71.  Back to cited text no. 9
    
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Maruyama K. The most important prognostic factors for gastric cancer patients: A study using univariate and multivariate analyses. Scand J Gastroenterol Suppl 1987;22:63-8.  Back to cited text no. 10
    
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Hohenberger P, Gretschel S. Gastric cancer. Lancet 2003;362:305-15.  Back to cited text no. 11
    
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Mori M, Shimada H, Gunji Y, Matsubara H, Hayashi H, Nimura Y, et al. S100A11 gene identified by in-house cDNA microarray as an accurate predictor of lymph node metastases of gastric cancer. Oncol Rep 2004;11:1287-93.  Back to cited text no. 12
    
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Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: Review and considerations for future directions. Ann Surg 2005;241:27-39.  Back to cited text no. 13
    
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de Manzoni G, Verlato G, Roviello F, Morgagni P, Di Leo A, Saragoni L, et al. The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients. Br J Cancer 2002;87:171-4.  Back to cited text no. 14
    
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Feng J, Wu YF, Xu HM, Wang SB, Chen JQ. Prognostic significance of the metastatic lymph node ratio in T3 gastric cancer patients undergoing total gastrectomy. Asian Pac J Cancer Prev 2011;12:3289-92.  Back to cited text no. 15
    
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Roder JD, Böttcher K, Busch R, Wittekind C, Hermanek P, Siewert JR. Classification of regional lymph node metastasis from gastric carcinoma. German Gastric Cancer Study Group. Cancer 1998;82:621-31.  Back to cited text no. 16
    
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Saito H, Fukumoto Y, Osaki T, Fukuda K, Tatebe S, Tsujitani S, et al. Prognostic significance of level and number of lymph node metastases in patients with gastric cancer. Ann Surg Oncol 2007;14:1688-93.  Back to cited text no. 18
    
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Kwon YM, Lim HT, Lee K, Cho BL, Park MS, Son KY, et al. Factors associated with use of gastric cancer screening services in Korea. World J Gastroenterol 2009;15:3653-9.  Back to cited text no. 19
    
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Liu C, Lu P, Lu Y, Xu H, Wang S, Chen J. Clinical implications of metastatic lymph node ratio in gastric cancer. BMC Cancer 2007;7:200.  Back to cited text no. 20
    
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Yu JW, Wu JG, Zheng LH, Zhang B, Ni XC, Li XQ, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma. J Exp Clin Cancer Res 2009;28:55.  Back to cited text no. 21
    
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Ding YB, Chen GY, Xia JG, Zang XW, Yang HY, Yang L, et al. Correlation of tumor-positive ratio and number of perigastric lymph nodes with prognosis of patients with surgically-removed gastric carcinoma. World J Gastroenterol 2004;10:182-5.  Back to cited text no. 22
    
23.
Bilici A, Seker M, Ustaalioglu BB, Yilmaz B, Doventas A, Salepci T, et al. Determining of metastatic lymph node ratio in patients who underwent D2 dissection for gastric cancer. Med Oncol 2010;27:975-84.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2]

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