The cancer has grown through the wall of the colon or rectum and is attached to or has grown into other nearby tissues or organs T4b. The cancer has grown through the mucosa into the submucosa T1 , and it may also have grown into the muscularis propria T2.
It has spread to 1 to 3 nearby lymph nodes N1 or into areas of fat near the lymph nodes but not the nodes themselves N1c. It has not spread to distant sites M0. The cancer has grown through the mucosa into the submucosa T1. It has spread to 4 to 6 nearby lymph nodes N2a. The cancer has grown into the outermost layers of the colon or rectum T3 or through the visceral peritoneum T4a but has not reached nearby organs. It has spread to 1 to 3 nearby lymph nodes N1a or N1b or into areas of fat near the lymph nodes but not the nodes themselves N1c.
The cancer has grown into the muscularis propria T2 or into the outermost layers of the colon or rectum T3. The cancer has grown through the mucosa into the submucosa T1 , and it might also have grown into the muscularis propria T2.
It has spread to 7 or more nearby lymph nodes N2b. The cancer has grown through the wall of the colon or rectum including the visceral peritoneum but has not reached nearby organs T4a. It has spread to at least one nearby lymph node or into areas of fat near the lymph nodes N1 or N2. The cancer may or may not have grown through the wall of the colon or rectum Any T. It might or might not have spread to nearby lymph nodes.
Any N. Evaluation of an abundant number of lymph nodes had been emphasized for accurate evaluation of lymph node status in colorectal cancer [ 1 - 3 , 12 - 15 ]. Fielding et al.
The current TNM staging system also recommended evaluation of at least 12 nodes for proper staging. In addition, evaluation of less than 12 nodes is included as a high-risk feature of stage II colorectal cancer and leads to the use of adjuvant chemotherapy after surgical resection [ 16 , 17 ]. Several studies have suggested examination of as many lymph nodes as possible with no fixed minimal requirement because number of examined lymph nodes is positively associated with increased survival [ 17 - 19 ].
The positive correlation between survival and number of lymph nodes might result in the staging migration and therapeutic benefit caused by removal of a high number of regional lymph nodes. However, wide variability has been reported in the number of examined lymph nodes. The number of examined lymph nodes has been reported to be influenced by extent of surgical resection, diligence of pathologic examination, patient-related factors such as body mass index, right or left-sided tumor location, tumor staging, and use of neoadjuvant treatment [ 21 - 23 ].
When the TNM staging system began considering the concept of TD, some previously considered lymph nodes were reclassified as TDs; consequently, the total number of lymph nodes decreased [ 12 , 13 ]. Different methods of node harvesting have been reported to increase lymph node yield from specimens for pathologic evaluation. Lisovsky et al.
They reported that this method improved correlation between lymph node staging and survival. Another attempt to increase the total number of examined lymph nodes involved the use of specific dyes, such as indocyanine green or methylene blue, during operation. This technique contributed to easy identification of lymph nodes from surrounding lymphoadipose tissue.
However, a more convenient method with proven efficacy is warranted for routine use in daily practice. LNR is defined as the ratio of the number of positive nodes to the total number of harvested nodes; the strength of this indicator is the value of these 2 parameters combined. LNR has been regarded as a good predictor of survival in stage III colon cancer, and its reliability was already demonstrated in other types of solid tumors [ 25 , 26 ].
Interestingly, Peng et al. Antithetically, some studies have reported that LNR was an independent prognostic factor for survival, regardless of the total number of examined lymph nodes [ 33 - 38 ]. Recent meta-analysis of 33 studies that included a total of 75, patients with node-positive colorectal cancer supported these findings. A standard reference value of LNR is required for universal use of LNR for predicting prognosis; however, there is no consensus on what this value should be.
In previous studies, LNR was presented as a categorical variable rather than a continuous one. Although the number of categories ranged from 2 to 10, the majority of studies divided all patients into 3 or 4 categories for better correlation to survival. The Japanese classification of colorectal carcinoma has suggested different lymph node staging classified by the location of metastatic lymph nodes rather than the number of metastatic lymph nodes.
In this system, metastatic lymph nodes in the pericolic region, along major vessels intermediate , and around the roots of involved major vessels apical were classified as N1, N2, and N3, respectively [ 39 ].
This method of N staging was included in the 4th edition of the TNM staging system, and lymph node metastasis around the roots of major vessels was classified as N3 regardless of the number of metastatic nodes.
However, this version of N3 was deleted from the 5th edition because of the complexity of dividing lymph node zones for pathologic evaluation. However, it remains controversial whether LND provides improved prognostic ability in node-positive colorectal cancer. This study classified patients with colon cancer according to the LND grading system: With TNM staging, Furthermore, some studies analyzed the clinical implications of LND according to tumor location.
One study that evaluated patients with stage III right-sided colon cancer showed that both proximal LND and N2 significantly influenced poor survival; however, they reported that LND had better prognostic ability than the TNM staging system [ 41 ]. Huh et al. Despite evidence supporting the use of LND as a classification for metastatic lymph nodes, it has not been generally applied in clinical practice compared to the TNM system because of its laborious nature and conflicting results from several retrospective studies suggesting that pathologic N staging was more significantly associated with survival than LND [ 43 ].
Suzuki et al. LND 2 and 3 in patients with node-positive colon cancer. Although some studies have emphasized the prognostic value of LND in patients with rectal cancer, the significance remains unclear. Kobayashi et al. Furthermore, Leibold et al. Lymph node metastases in the proximal area around the major feeding vessels resulted in significantly lower DFS; therefore, they strongly suggested that LND should be considered in rectal cancer treated by CRT.
They also recommended intensified adjuvant chemotherapy in patients with rectal cancer with proximal lymph node metastases. Several studies have evaluated the association between survival and apical lymph node metastases around the main feeding artery LND 3 ; they showed that patients with LND 3 had significantly poorer survival rates than patients without apical node metastases.
In addition, this specific subgroup of patients with LND 3 had similar survival rates as those with stage IV disease that achieved R0 resection [ 42 , 47 ]. Consequently, they suggested that lymph node metastases located around the main vessel should be categorized as systemic metastasis rather than as regional node metastasis based on the survival data and anatomic background.
Some studies evaluated the metastatic patterns of lymph nodes, which were grouped according to tumor location based on the Japanese classification of colorectal carcinoma [ 39 ]. They evaluated lymph node metastatic patterns in detail and attempted to determine adequate surgical extent based on tumor location.
Park et al. They reported that ileocolic lymph node metastases were the most common in cecal and ascending colon cancer; however, 6. They also evaluated the value of sigmoid mesenteric lymph node metastases in patients with rectal cancer and showed that Although these aberrant lymph node metastases did not influence survival in either study, the findings emphasize that removal of these nodes is required for proper staging, but not for cure.
The treatment of lateral pelvic node LPN metastasis is still controversial. In Japan, prophylactic or therapeutic lateral pelvic node dissection LPND have been routinely recommended for advanced lower rectal cancer to reduce local and even systemic failure [ 50 , 51 ].
However, they did not perform preoperative CRT in these rectal cancer patients [ 52 ]. On the other hand, in western countries, preoperative CRT and TME are regarded as the standard treatment in locally advanced rectal cancer [ 53 , 54 ]. It is primarily due to effective local control by preoperative CRT, higher morbidity rates of LPND without improving oncologic results, therefore implying systemic disease [ 55 , 56 ].
However, preoperative CRT may sterilize lymph nodes in the pelvic sidewall. Recently, some collaborative studies between western and eastern countries were published for evaluating the significance of metastatic LPN on survival rates. Ogura et al. However, the Japanese classification of colorectal carcinoma considers it a regional, stage III disease [ 39 ].
Therefore, optimal management for PALN metastasis is still not clearly defined based on these different views. Several case series have reported favorable survival rates by performing paraaortic lymph node dissection PALND in selected patients [ 63 - 65 ]. The outcomes featured tolerable morbidity rates ranged from 7.
Choi et al. Five-year OS rate was In addition, the presence of two or less PALN metastases was the only prognostic factor for better survival.
Chemotherapy with or without radiation therapy has been used as a form of salvage therapy for patients with PALN metastasis [ 66 - 68 ]. However, Min et al. There was no multi-center, randomized study for these two different approaches to treat PALN metastasis.
Further study is needed to conclude these controversies. TDs were described as separate tumor nodules identified in the pericolic or perirectal adipose tissue without evidence of lymph node.
The concept of TD has been undergoing changes in the past several decades, especially since it was included in the TNM staging system. In the 8th edition, TD was defined in further detail [ 13 ]. The definition stated that in the presence of an identifiable vessel wall or neural structure, a nodule was classified as lymphovascular invasion or perineural invasion, respectively Table 1.
To help detect vessel walls, the use of special stains may be considered in addition to routine hematoxylin-eosin stains. These changes were introduced with the concept of TD in the TNM staging system because many studies suggest that TDs are associated with advanced tumor growth and decreased survival [ 70 - 73 ]. In addition, Ueno et al. They also suggested that TDs showed similar survival rates as node-positive disease. However, large interobserver variability has persisted in interpretation of TDs and differentiation from discontinuous tumor spread, totally replaced lymph node, and VI.
Therefore, further studies are needed to increase interobserver pathologist agreement in diagnosis of TDs. ECI has been reported as a valuable prognostic factor related to inferior survival [ 75 - 77 ]. This finding was based on the morphologic features of lymph nodes rather than on the number or location of metastatic lymph nodes.
ECI is defined as penetration of tumor cells from the nodal capsule into the perinodal fatty tissue. Therefore, ECI might reflect the aggressiveness of tumor biology and supplement the current lymph node staging system [ 78 ].
ECI has also emerged as a predictive factor in various solid tumors [ 79 , 80 ]. In a recent meta-analysis that analyzed 1, patients with colorectal cancer from 13 studies, ECI was strongly correlated with advanced tumor staging and differentiation and was associated with significantly worse OS HR, 1. Universal interobserver agreement is required to evaluate ECI in colorectal cancer. During isolation of lymph node, pathologists should include adipose tissue around lymph nodes.
ECI and TDs exist in the adipose tissue surrounding lymph nodes. Lymph nodes near the colon and rectum are called regional lymph nodes. All others are distant lymph nodes that are found in other parts of the body. N1c: There are nodules made up of tumor cells found in the structures near the colon that do not appear to be lymph nodes.
The "M" in the TNM system describes cancer that has spread to other parts of the body, such as the liver or lungs. This is called metastasis. M1a: The cancer has spread to 1 other part of the body beyond the colon or rectum. M1b: The cancer has spread to more than 1 part of the body other than the colon or rectum.
Doctors also describe this type of cancer by its grade G. The grade describes how much cancer cells look like healthy cells when viewed under a microscope. The doctor compares the cancerous tissue with healthy tissue. Healthy tissue usually contains many different types of cells grouped together.
If the cancer looks similar to healthy tissue and has different cell groupings, it is called "differentiated" or a "low-grade tumor. G2: The cells are somewhat like healthy cells, called moderately differentiated. Stage 0: This is called cancer in situ. The cancer cells are only in the mucosa, or the inner lining, of the colon or rectum.
Stage I: The cancer has grown through the mucosa and has invaded the muscular layer of the colon or rectum. It has not spread into nearby tissue or lymph nodes T1 or T2, N0, M0. Stage IIA: The cancer has grown through the wall of the colon or rectum but has not spread to nearby tissue or to the nearby lymph nodes T3, N0, M0.
Stage IIB: The cancer has grown through the layers of the muscle to the lining of the abdomen, called the visceral peritoneum. It has not spread to the nearby lymph nodes or elsewhere T4a, N0, M0. Stage IIC: The tumor has spread through the wall of the colon or rectum and has grown into nearby structures. It has not spread to the nearby lymph nodes or elsewhere T4b, N0, M0.
Stage IIIA: The cancer has grown through the inner lining or into the muscle layers of the intestine. It has spread to 1 to 3 lymph nodes or to a nodule of tumor cells in tissues around the colon or rectum that do not appear to be lymph nodes but has not spread to other parts of the body T1 or T2, N1 or N1c, M0; or T1, N2a, M0. Stage IIIB: The cancer has grown through the bowel wall or to surrounding organs and into 1 to 3 lymph nodes or to a nodule of tumor in tissues around the colon or rectum that do not appear to be lymph nodes.
Stage IVC: The cancer has spread to the peritoneum. It may also have spread to other sites or organs any T, any N, M1c. Recurrent: Recurrent cancer is cancer that has come back after treatment. The disease may be found in the colon, rectum, or in another part of the body. If the cancer does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.
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