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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2012  |  Volume : 55  |  Issue : 1  |  Page : 38-42
Are we achieving the benchmark of retrieving 12 lymph nodes in colorectal carcinoma specimens? Experience from a tertiary referral center in India and review of literature


1 Department of Pathology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India
2 Centre for Cancer Epidemiology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India
3 Department of GI and HPB Surgical Oncology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India

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Date of Web Publication11-Apr-2012
 

   Abstract 

Introduction: The number of lymph nodes (LNs) retrieved from a specimen of colorectal carcinoma may vary. Factors that can possibly affect LN yield are age of the patient, obesity, location of the tumor, neoadjuvant therapy, surgical technique and pathologist's handling of the specimen. Aim: The aim of our study is to look at lymph node retrieval from colorectal cancer (CRC) specimens in our hands and review the literature. Materials and Methods: From May 2010 to January 2011, a total of 170 colorectal carcinoma cases were operated in our institute. Type of the surgeries, lymph node yield was looked at. Results: There were 103 (60.6%) males and 67 (39.4%) females. The commonest age group was 50-59 years (30.6%). The surgeries included 107 surgeries for rectal carcinoma (63%) and 63 surgeries for colonic carcinoma (37%). Sixty six (38.8%) cases had received preoperative chemoradiotherapy, whereas 104 (61.2%) cases were without adjuvant therapy. The total lymph node positivity (metastatic disease) was 44.7% .The overall mean lymph node yield was 12.68 (range 0-63; median 11). The mean lymph node harvest in the age group < 39 was 15.76 whereas, the lymph node harvest in the group more than 39 years old was 11.90. ( statistically significant; P=0.03). The mean lymph node yield from specimens of rectal cancers (10.30) was lower than the mean lymph node yield from specimens for colonic cancers (16.71);( statistically significant, P<0.01). There was also statistically significant difference between the mean LN yield in chemoradionaiive cases (14.63) and in the cases where neoadjuvant therapy was received, (9.59); P<0.01. Conclusion: Pathologist while assessing a specimen of CRC should aim to retrieve a minimum of 12 LN. Surgical expertise and diligence of the pathologists remain two main alterable factors that can improve this yield. Neoadjuvant or preoperative radiotherapy can yield in less number of nodes.

Keywords: Colorectal carcinoma, lymph node harvest, gross examination

How to cite this article:
Deodhar KK, Budukh A, Ramadwar M, Bal MM, Shrikhande S V. Are we achieving the benchmark of retrieving 12 lymph nodes in colorectal carcinoma specimens? Experience from a tertiary referral center in India and review of literature. Indian J Pathol Microbiol 2012;55:38-42

How to cite this URL:
Deodhar KK, Budukh A, Ramadwar M, Bal MM, Shrikhande S V. Are we achieving the benchmark of retrieving 12 lymph nodes in colorectal carcinoma specimens? Experience from a tertiary referral center in India and review of literature. Indian J Pathol Microbiol [serial online] 2012 [cited 2019 Sep 20];55:38-42. Available from: http://www.ijpmonline.org/text.asp?2012/55/1/38/94853



   Introduction Top


Optimal staging of primary colorectal carcinoma is crucial in prognosis as well as for treatment planning. Retrieval of adequate number of lymph nodes (LNs) from a specimen of colorectal surgery is an integral part of this process. LN metastasis is highly predictive of outcome and is a major determinant of adjuvant therapy. [1]

The number of LNs retrieved from a specimen of colorectal carcinoma may vary. Factors that can possibly affect LN yield are age of the patient, obesity, location of the tumor, neoadjuvant therapy, surgical technique, and pathologist's handling of the specimen.

National Cancer Institute guidelines suggests that a minimum of 12 LNs are required to accurately determine whether a patient has a positive LN or not. [2] In 2007, the National Quality Forum endorsed the harvest of >12 LNs as a standard quality indicator for colorectal cancer (CRC) resection specimen. [3] The aim of our study is to look at LN retrieval from CRC specimens in our hands and review the literature.


   Materials and Methods Top


From May 2010 to January 2011, a total of 170 colorectal carcinoma cases were operated in our institute. All had been done by or supervised by surgeons who are trained in and having wide experience in CRC surgery. [4]

The specimens are sent to the department of pathology in fresh state in plastic sealed bags. They are opened and fixed for a minimum of 24 hours. After fixation, the standard grossing protocol is followed in inking the non-peritonealized surface [Figure 1], serially sectioning the tumor and assessing the depth of tumor infiltration and the circumferential resection margin wherever applicable. After laying the tumor slices on the grossing table, appropriate selection of the blocks is done where the tumor infiltration in the wall is judged to be maximum. The LNs are carefully dissected from the mesentry including the apical node, keeping in mind that the LNs in the bowel slices sections are also to be examined [Figure 2]. All LNs, however small, are processed and examined histologically. Apart from careful manual palpation and dissection of nodes, other LN retrieval methods are not used. It is a routine practice during the surgery either to mark the vessels with ligatures kept long, or apply multiple clips to the pedicle.
Figure 1: Specimen of abdominoperineal resection (APR). The non-peritonealized surface is inked

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Figure 2: Serial slices of the tumor in the bowel. This is to select the most appropriate block where the tumor invasion in the bowel wall is maximum, as well as to retrieve the nodes. Yellow arrows show lymph nodes in the mesentery

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Requirement of serial sections is judged in individual case where the full section of the LN was not seen on the slide.

Abdominoperineal resection (APR), Anterior resection (AR), Low AR, and Ultra low AR are taken as surgeries for rectal carcinomas. All others (left hemicolectomy, right hemicolectomy, proctocolectomy, sigmoid colectomy, and others) are taken as surgeries for colonic tumors. The codes used for different surgeries are code 1-APR, code 2-AR, code 3-low AR, and code 4-ultra low AR, code 5-Left hemicolectomy, code 6- Right Hemicolectomy, code 7- proctocolectomy, code 8-sigmoid colectomy, code 9-others.

Proctocolectomies are generally carried out for familial adenomatosis polyp patients. The category of "others" included transverse colectomies, Hartman's procedure, etc. "t" test was applied to compare the mean between the two groups.


   Results Top


There were 103 (60.6%) males and 67 (39.4%) females. The commonest age group was 50 to 59 years (30.59%) [Table 1].
Table 1: Age and sex distribution of the operated CRC patients

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The surgeries included surgeries for rectal carcinoma (107) and for colonic carcinoma (63). There were 40 APR cases (23.53%); 29 AR cases (17.05%); 30 Low AR cases (17.64%); and 8 ultra low AR cases (4.71%) [Table 2].
Table 2: Mean and median lymph nodes by treatment type in CRC patients

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Sixty six (38.8%) cases had received preoperative neoadjuvant therapy, while 104 (61.2%) cases were cases without adjuvant therapy [Table 3]. The total LN positivity (metastatic disease) was 44.7% [Table 2].
Table 3: Comparison of the mean lymph nodes by age group and treatment

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The overall mean LNyield was 12.68 (range, 0-63; median, 11) [Table 4].
Table 4: Mean and median lymph nodes in operated CRC patients by age group

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The mean LN harvest in the age group <39 years was 15.76, whereas the LN harvest in the age group more than 39 years old was 11.90 (Statistically significant; P=0.03).

There was statistically significant difference between the mean LN yield from specimens of rectal cancers (10.30) and from specimens for colonic cancers (16.71); (P<0.001). There was also statistically significant difference between the mean LN yield in chemoradionaiive cases (14.63) and in the cases where neoadjuvant therapy was received; (9.59) (P=0.0005).


   Discussion Top


Finding of a metastatic LN in a colorectal carcinoma specimen places it in a stage III disease (as against stage II, which is node negative disease). Stage III disease are likely to receive chemotherapy (if age and comorbidity allow) which is probably beneficial, mildly toxic, and costly. [5] More importantly, it has been shown that clinical outcome is linked to LN harvest in stage II disease. Numerous studies have shown that conventional pathologic examination of increased numbers of LNs is itself associated with an increased survival advantage in stage II disease, [6] indicating a positive effect of optimal mesenteric resection by the surgeon, optimal LN harvest from the resection specimen by the pathologist, or both.

In 2007, the National Quality Forum listed the presence of at least 12 LNs in a surgical resection among the key quality measures for colon cancer in the United States. If less than 12 LN are found, regrossing is recommended. [7] In our institution, the gastrointestinal surgical audit is presented every month in the multidisciplinary meeting and if the LN yield is less than 12, our surgical colleagues do not miss the chance to point it out.

The number of LNs retrieved from a specimen of colorectal carcinoma may vary. Factors that can possibly affect LN yield are age of the patient, obesity, location of the tumor, neoadjuvant therapy, surgical technique, and pathologist's handling of the specimen.

Rajput et al., in an elaborate study of colonic cancers, noted that 92% of National Comprehensive Cancer Network (NCCN) centers had achieved this benchmark of >12 LNs. In this study, the univariate analysis showed that primary site in the distal left colon, low stage of the disease, and high body mass index (BMI of >30) all were less likely to meet the target of 12 LNs. [8] However, in another study, it has been shown that obesity does not influence LN yield. [9]

In a large population-based study (which included both colonic as well as rectal cancers, n=153 483), Chou et al. noted overall mean number of LNs evaluated (+SD) was 12 + 9.3, with a mean (+SD) of 12.4 + 9.4 LNs for patients with colon cancer and 10.2 + 8.8 LNs for patients with rectal cancer. They also noted that distally located, early colon cancers are less likely to meet the benchmark yield of 12 LNs. [10]

In the study by Chou et al., age was a consistently important determinant of the LN yield. The mean number of LNs harvested from colon and rectal cancer patients >70 years of age was 11.7 and 9.3, respectively; and for every 10 year incremental increase in age, there was an average reduction of 9% in LN harvest in both cohorts. [10] These authors hypothesized that older patients with higher comorbidities may place undue pressure on the surgeon to perform less extensive surgery. However, Tekkis et al. hypothesized alternative reason that LNs in older patients may undergo a process of involution. [11]

Morcos et al. also noted distal rectal cancer and female sex adversely affected the LN yield. [12] However, in their study age, tumor stage and grade, type of operation, and surgical delay did not affect the number of LNs removed.

In our data, BMI was not recorded. The commonest age group in our data was between 50 and 59 years. Our data shows that the mean LN yield of rectal cancer specimens (codes 1-4) is 10.30 which is lesser than LN yield in colonic cancers (mean, 16.71), which is statistically significant (P<0.01). Our data also show statistically significant difference in the mean LN yield(15.76 and 11.90) between the age groups ≤39 and >39 years, respectively (P=0.03).

Another interesting observation has been high LN positivity (metastasis) in proctocolectomies and sigmoid colectomies [Table 3].

Although, as depicted in the literature, distal colonic cancers, early stage, age, sex, BMI, and type of operation are factors which influence the LN yield, they still are the "non alterable factors." Recently, Leung et al. showed that factors such as age, T stage, previous surgery, and surgical approach (laparoscopic vs open surgery) do not affect LN yield; but the operating surgeon and examining pathologist have significant impact on the number of LN harvested. [13]

Operating surgeon and handling the specimen by the pathologist remain two crucial (so called "alterable") factors. [10] As stated earlier, in a study by Leung et al., these two were the only two factors found to have significant impact on the LN yield. [13] Storli et al. commented that specimen handling is the foremost important factor in colon cancer specimen. [14]

The seminal work by Heald and Ryall in showing total mesorectal excision for rectal cancer, resulting in low recurrence and improved survival, has become a gold standard for number of years now. [15]

In an interesting study, depicting barriers in optimal assessment of LNs, Wright et al. found that only 57.9% of the pathologists in and around Ottawa (Canada) were aware of the guidelines regarding the optimum LN yield; moreover, only 25% identified that a minimum of 12 LNs are necessary for accurate designation of node negativity. Lack of time, lack of pathologists, and inadequate length of colon or mesocolon are some of the perceived barriers in LN harvest. They also stated that there is a need for educational strategy for increasing awareness of these requirements. [16]

We have learnt certain things out of this audit -

  1. If a relook gross examination is done, this needs to be mentioned in the report. This has not been our consistent practice before.

    This practice has its own value even if a difference in staging is not significant.
  2. Our median LN yield is reasonable, but it can be improved.
  3. Retrieval of LNs needs no sophisticated machines, high resource techniques; only investment of time followed by a good H and E is required.


In a teaching institution, a fresh lot of trainees come to the pathology department at a regular interval and the "so called mundane" job of grossing is assigned to the trainees in pathology. However, the faculty or the teaching staff has a particular responsibility to train and supervise the resident staff in grossing techniques and instill a culture of meticulous grossing in them regarding the LN harvest, as it has an impact on the diagnosis and prognosis. Adequate amount of time ought to be spent on the specimen to try and achieve a harvest of at least 12 LNs.

Dissecting as many nodes as possible gives a better TNM staging, especially in stage II. In our opinion, trying to preserve part of the specimen for mounting and undergraduate teaching should take second priority over attempt to get maximum LN yield.

With regards to pathology technique, the NCCN recommends that if initially <12 LNs are found, then the pathologist should submit more tissue. If still the yield is less, then a comment should be added to the report stating an extensive search is carried out. [7]

When we examined the reports which yielded less than 12 nodes (with no metastasis), we found a total 61 cases. Of which, in 32 cases (52.5%), neoadjuvant therapy (chemotherapy, radiotherapy) has been given. In 13 of total 61 cases (21.3%), histopathology reports mentioned specifically that a relook gross examination/or extensive search for nodes has been carried out.

Of these, in four cases, 1, 2, 4, and 6 additional reactive nodes were found. In nine cases, even after regrossing, no further nodes were found. None of these cases showed metastatic nodes after regrossing (one showed acellular mucin pools); hence, no change in the stage was detected.

Certain fat clearance techniques using xylene and alcohol are shown to increase recovery of more nodes, with corresponding increase in positive nodes. [17]

However, these techniques are time consuming and need expertise. Feasibility in a laboratory handling high volume may not be practicable. Recently, a novel technique of postoperative intra-arterial methylene blue injection of colorectal carcinoma specimens has shown significant increase in the number of LNs recovered from the specimen. [18] In our study, we have not used any fat clearance techniques.

Our data showed that mean LN yield in cases receiving preoperative neoadjuvant therapy (chemoradiotherapy) is 9.54. However, this is in keeping with the quoted literature. [10],[11],[12],[19] Tekkis et al. observed mean LN harvest of 9.8, 12.1, and 11.8 for patients who received preoperative radiation, postoperative radiation, and no radiation, respectively. [11] Chou et al. observed 25% average reduction in the LN harvest when comparing preoperative radiation and no radiation group. [10]

The reason for a low LN yield in these cases could be inflammation, tissue fibrosis, and/or shrinkage of the LNs. [19] It has also been suggested that tumor positive LN ratio is more informative. [20],[21]


   Conclusion Top


Pathologist while assessing a specimen of CRC should aim to retrieve a minimum of 12 LNs. A wider awareness is necessary of this benchmark requirement.

Distal colonic location, small tumor volume, and early stage are some of the nonalterable factors adversely affecting the LN yield. However, surgical expertise and diligence of the pathologists remain two main alterable factors that can improve this yield.

Neoadjuvant or preoperative radiotherapy can yield less number of nodes.

 
   References Top

1.Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000;124:979-94  Back to cited text no. 1
    
2.Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Miedema B, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:583-96.  Back to cited text no. 2
    
3.National Quality Forum. Appendix A. Specifications of the National Voluntary Consensus Standards for breast and colon Cancer. Available from: http//www.qualityforum.org/pdf/cancer/txbreast-colonAppA-Specsvoting01-18-07. [Last accessed on 2008 June 27].  Back to cited text no. 3
    
4.Shrikhande SV, Saoji RR, Barreto SG, Kakade AC, Waterford SD, Ahire SB, et al. Outcomes of resection for rectal cancer in India: The impact of double stapling technique. World J Surg Oncol 2007;21:5-35.  Back to cited text no. 4
    
5.Moertel CG, Fleming TR, MacDonald JS, Haller DG, Tangen CM, Laurie JA, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: A final report. Ann Intern Med 1995;122:3216.  Back to cited text no. 5
    
6.Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: Systematic review. [Review]. J Natl Cancer Inst 2007;99:43341.   Back to cited text no. 6
    
7. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in Oncology. Principles of pathologic review for colon and rectal cancer. Available from: http://www.nccn.org/professionals/physician_gls/PDF/rectal; http://www.nccn.org/professionals/physician_gls/PDF/colon.  Back to cited text no. 7
    
8.Rajput A, Romanus D, Weiser MR, Ter Veer A, Niland J, Wilson J, et al. Meeting the 12 Lymph node Benchmark in Colon Cncer. J Surg Oncol 2010;102:3-9.  Back to cited text no. 8
    
9.Linebarger JH, Mathiason MA, Kallies KJ, Shapiro SB. Does obesity impact lymph node retrieval in colon cancer surgery? Am J Surg 2010;4:478-82.  Back to cited text no. 9
    
10.Chou JF, Row D, Gonen M, Liu Yi-Hai, Schrag D. Clinical and Pathologic Factors That Predict Lymph Node Yield From Surgical Specimens in Colorectal Cancer. A Population Based Study. Cancer 2010;116:2560-70.  Back to cited text no. 10
    
11.Tekkis P, Smith JJ, Heriot AG, Darzi AW, Thompson MR, Stamatakis JD. A national study on lymph node retrieval in resectional surgery for colorectal cancer. Dis Colon Rectum 2006;49:1673-83.  Back to cited text no. 11
    
12.Morcos B, Baker B, Masri MA, Haddad H, Hashem S. Lymph node yield in rectal cancer surgery: Effect of preoperative chemoradiotherapy. Eur J Surg Oncol 2010;36:345-9.  Back to cited text no. 12
    
13.Leung AM, Scharf BS, Vu HN. Factors affecting number of lymph nodes harvested in colorectal Cancer. J Surg Res 2011;168:224-30.  Back to cited text no. 13
    
14.Storli K, Lindboe CF, Kristopherson C, Kleiven K, Sondenna K. Lymp node harvest in colon cancer specimen depends on tumour factors, patients and doctors, but foremost on specimen handling. APIMS 2011;219:127-34.  Back to cited text no. 14
    
15.Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;28:1479-82.  Back to cited text no. 15
    
16.Wright FR, Law CH, Last LD, Ritacco R, Kumar D, Hsieh E, et al. Barriers to Optimal Assessment of Lymph Nodes in Colorectal Cancer Specimens. Am J Clin Pathol 2004;121:663-70.  Back to cited text no. 16
    
17.Haboubi NY, Abdalla SA, Amini S, Clark P, Dougal M, Dube A, et al. The novel combination f fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: A preliminary study. Int J Colorectal Dis 1998;13:99-102.  Back to cited text no. 17
    
18.Tornroos A, Shabo I, Druvefors B, Arbman G, Olsson H. Postoperative intra-arterial methylene blue injection of colorectal cancer specimens increases the number of lymph nodes recovered Histopathology 2011;58:408-13.  Back to cited text no. 18
    
19.Shia J, McManus M, Guillem JG, Leibold T, Zhou Q, Tang LH, et al. Significance of Acellular Mucin Pools in Rectal Carcinoma After Neoadjuvant Chemoradiotherapy. Am J Surg Pathol 2011;35:127-34.  Back to cited text no. 19
    
20.Peschaud F, Benoist S, Julie C, Beauchet A, Penna C, Rougier P, et al. The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. Ann Surg 2008;248:1067-73.  Back to cited text no. 20
    
21.Rosenberg R, Friederichs J, Schuster T, Gertier R, Maak M, Becker K, et al. Prognosis of patietns with colorectal cancer is associated with lymph node ratio: A single-center analysis of 3026 patients over a 25 year time period. Ann Surg 2008;248:968-78.  Back to cited text no. 21
    

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Correspondence Address:
Kedar K Deodhar
Department of Pathology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai - 400 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.94853

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