Influence of the Number of Lymph Nodes Examined on the Prognosis of Patients with Dukes’ B and C Colorectal Carcinoma

DISCUSSION

It has been shown in many studies that the number of the lymph nodes examined is an independent prognostic factor affecting the survival rate of the patients with Dukes’ B large intestinal carcinoma. Caplin et al.^[3] analyzed data from 211 patients with Dukes’ B large intestinal carcinoma and found that the overall survival rate of the patients with fewer than 6 lymph nodes examined was significantly decreased, and that their survival curve was similar to that of the Dukes’ C patients. Prandi et al.^[4] divided 3,248 cases with Dukes’ B and C large intestinal carcinoma into 4 groups, based on the number of the lymph nodes examined (ranging from 0 to 7, 8 to 12, 13 to 17 and over 18). The 5-year survival rate of the Dukes’ B patients with a number of less than 7 examined was much lower compared to the patients with the same tumor stage. However it was still higher than that of the Dukes’ C patients. There was no significant difference between the survival rates of Dukes’ C patients in the different groups.

Our findings were in accord with the reports from the literature, indicating that the 5-year survival rate of the patients with fewer nodes screened out (≤10) was obviously lower than those with more nodes examined (>10). Further analysis revealed that the number of the lymph nodes examined mainly affected the prognostic efficacy for patients with Dukes’ B large intestinal carcinoma. Concerning those with Dukes’ C large intestinal carcinoma, the number of the nodes examined had no effect on the prognosis.

The poor prognosis of patients with a lower rate of lymph nodes screened-out may relate to the following factors. First, the scope of surgical clearing-up may not be sufficient, resulting in fewer lymph nodes screened in the operative region. So positive lymph nodes might remain. Moreover pathologists may miss some of the positive lymph nodes when examining the pathological samples. Missed identification of positive lymph nodes may result in an incorrect staging of some Dukes’ C patients as Dukes’ B, thus incorrectly lowering the survival rate of some Dukes’ B patients. This hypothesis has been accepted by many scholars. Goldstein et al.^[5] reported that if more lymph nodes were examined, the positive lymph node rate was higher. Our results indicated that in the patients with less than 11 nodes screened-out, the rate of positive lymph nodes detected was 35.1%, whereas, when the number of examined nodes was not less than 11, the positive rate of lymph nodes detected was 50.4%. There was a significant difference between the two groups. It is suggested that examination of too few nodes may decrease the rate of detecting positive lymph nodes, thus incorrectly dividing some of the patients with Dukes’ C into Dukes’ B. In addition, the findings of our research revealed that, although the 5-year survival rate of the Dukes’ B carcinoma patients with fewer lymph nodes examined was lower compared to the patients of other groups, it was still higher than that of the Dukes’ C patients. It demonstrated that in the Dukes’ B cancer patients with a low number of lymph nodes examined only part of them were the Stage-C patients incorrectly divided into the group with Stage-B patients.

Examination of too few nodes may bring about missed diagnosis of a portion of the positive lymph nodes, causing incorrect division of the patients with Dukes’ C into those with Dukes’ B. Therefore, harvesting the lymph nodes in as many regions as possible is a precondition for making a correct decision concerning lymph node metastasis. However, there is still a lack of agreement on the least number of nodes to be examined for a correct tumor staging^[6-9].This may result from a difference in the type of patients, modes of operation, scope of lymphatic scavenge, and proportion of colorectal cancer etc. in various studies.

Our findings indicated that the number of lymph nodes examined had a close relationship with the tumor size, depth of the infiltration and especially the tumor site. The mean number of lymph nodes examined in the colon carcinoma patients was 17.51 ±12.79, whereas that of the rectal cancer patients was only 11.09±6.17 (P = 0.000). This difference most probably ensues because there is an extensive scope of mesentery scavenge with colon carcinoma, and less in the mesenteries with rectal cancer, because of a limitation of clearance of nodes in the pelvic area. Therefore, if there are different tumor types in various studies, the number of the lymph nodes also might be different. Caplin^[3] and Prandi et al.^[4] also recognized the problem, and they suggest that the postoperative number of the lymph nodes examined was significantly larger in colon carcinoma patients than in those with rectal cancer. Like other researchers, however, they did not address the two questions, i.e. what is the least number of nodes to be examined separately for colon carcinoma and rectal cancer. Obviously, this might result in a change in their research conclcusions.

In our study, when the data from these cancers, i.e. colon carcinoma and rectal cancer, are analyzed together, the 5-year survival rate of the Dukes’ B patients would be significantly decreased if the number of nodes examined is less than 11. However, if the two cases are investigated separately, the number of nodes examined in the rectal cancer patients was less than 9, and that in the colon carcinoma patients was less than 13, with a significantly low survival rate. So it is considered that to guarantee the exact staging, and so as to not result in a missed detection of positive lymph nodes, the least number of nodes for a diagnosis of the patients with the rectal cancer should be 9 and for colon carcinoma 13.

It has been reported that use of a special detection method will result in a harvest of more lymph nodes. For example, clearing of fat can significantly increase the number of lymph nodes examined from surgical samples, and at the same time the number of positive lymph nodes found may also increase. It was reported by Herrera-Ornelas et al.^[10], that of the positive lymph nodes detected by a clearing-up process, 78% of the lymph nodes had a diameter of less than 5 mm, and in a routine examination these nodes may easily be missed, suggesting that this method can ensure a more accurate tumor staging. Since the method is complicated and time-consuming, requiring 9 to 10 days for dehydration and degreasing, it has not received extensive clinical application. Moreover, other methods such as serial sectioning of lymph nodes, immunohistochemical staining and gene technology etc.^[11] have been employed to locate tumorous micrometastic foci. However, at present there is no consensus on the importance of micrometastasis on the prognosis.

Fisher et al.^[12] employed an immunohistochemical method to examine 399 Dukes’ A and B patients for whom no lymphatic metastasis had been detected previously using routine staining. Results showed that the micrometastatic foci were found in the lymph nodes of 72 patients. However, there was no difference in the overall survival rate and/or disease-free survival rate between the 72 patients and other patients. It is thought that some of the above-mentioned procedures may have flaws, and some prognostic data have not yet been validated. So an extensive clinical application is unadvisable at present. Nevertheless, in cases where no lymph-node metastasis is found, but where the patient’s condition is highly doubtful, such as in rectal cancer with < 9 lymph nodes examined, in colon carcinoma with < 13 nodes inspected, or with high-risk factors of lymphatic metastasis (e.g. a large size or deep tumor infiltration, a poorly differentiated and an infiltrating type tumor etc., see Table 4), further technical measures, such as fat clearance etc., should be conducted to find possible missed lymph nodes and thus enhance the staging accuracy.

Over the past few years, researchers have attempted to employ sentinel-node biopsy in diagnosis of large intestinal carcinoma. The findings have shown that compared to breast cancer or melanoma, it was impossible to predict the lymph node condition and to guide the scope of the lymphatic scavenge during treatment of patients with large intestinal carcinoma patients. In one study, the drainage area where lymph node metastasis frequently occur was stained during a sentinel-node biopsy. This procedure may be helpful for the pathologist to more carefully inspect this area, raising the positive-node detection rate^[13].

In conclusion, the number of lymph nodes examined is a prognostic factor influencing the survival rate of patients with Dukes’ B large intestinal carcinoma. To ensure an accuracy of tumor staging, a total of 9 and 13 lymph nodes should be screened out for rectal cancer and colon carcinoma patients, respectively, providing for a correct basis for further adjunctive therapy.