Lymph Nodes

What are Lymph Nodes (LN)?

Lymph nodes (LN) are small, bean-shaped organs found throughout the body. They have many important roles as a part of the immune and cardiovascular systems. Unfortunately, LN are a common secondary site of cancer. This is especially true in gastric cancer, because the LN near the stomach are clustered together in close bunches near many blood vessels. These bunches are connected to each other by small canals, making an easy path for the disease to spread. Removing lymph nodes can help to prevent the spread of cancer. This is why it is important that they are removed in gastric cancer surgery. The N-stage in TNM tumor staging tells us the number of LN that have developed cancer.

What is a lymphadenectomy?

A lymphadenectomy is a surgery that takes out lymph nodes. It is usually done with a gastrectomy. There are two lymphadenectomy techniques that are important to gastrectomy:

D1: this surgery is less extensive. It only takes out the LN found closest to the stomach.
D2: this surgery is more extensive. It takes out the LN found closest to the stomach, as well as LN found close to major blood vessels.

Why are LN important?

There are a number of unanswered questions about the role of LN in gastric cancer surgery. Dr. Coburn’s work shows that sometimes there is not enough information available for surgeons to know how many LN to remove to keep their patients healthy, especially in North America.

Not removing enough LN can mean a few things for the patient:

Some of the cancer is still left in the body
It can be hard to tell how far the cancer has spread from the primary site

These important issues are addressed in the studies below.

Significant Regional Variation in Adequacy of Lymph Node Assessment and Survival in Gastric Cancer (2006)

https://www.ncbi.nlm.nih.gov/pubmed/17001662

Coburn, Natalie G., et al. “Significant regional variation in adequacy of lymph node assessment and survival in gastric cancer.” Cancer 107.9 (2006): 2143-2151. Available from: doi: https://doi.org/10.1002/cncr.22229
What were they trying to learn?
1. The American Joint Commission on Cancer has made recommendations for surgeons about the number of LN to take out.
2. This was done to standardize the number of LN removed, so there is no confusion and all patients receive the same treatment.
3. These guidelines are called the Adequate Lymph Node Assessment (ALNA) criteria. According to ALNA, at least 15 lymph nodes should be assessed. This means that ideally, all surgeons around the world should take out at least 15 lymph nodes when doing a gastric cancer surgery.
4. This study wanted to know if surgeons in North America were following these ALNA criteria and how many LNs they were removing.
How did they address their question?
1. This paper analyzed a total of 10,807 patients who had surgery for gastric cancer in different regions across America.
What did they find? Why is this important?
1. Overall, they found that not enough LN were being assessed. The average number of lymph nodes assessed was only 9-10.
2. A low number of LN assessed is associated with lower overall survival.
3. It is estimated that 11% of patients miss out on receiving chemotherapy which could have helped them, because too few lymph nodes were assessed to qualify them for treatment.
4. So, this paper showed that surgeons in North America should be assessing more lymph nodes.

Lymph Nodes and Gastric Cancer (2009)

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jso.21224

Coburn, Natalie G. “Lymph nodes and gastric cancer.” Journal of surgical oncology 99.4 (2009): 199-206. Available from: doi: https://doi.org/10.1002/jso.21224
What questions is this paper trying to answer?
1. This paper discusses the role of lymph nodes in diagnosing and treating gastric cancer.
2. It reviews the methods used to evaluate lymph node status. This includes the number of lymph nodes assessed.
3. The use of D1or D2 lymphadenectomies.
4. Finally, the paper looked at the effects of chemotherapy before and after surgery on lymph nodes in gastric cancer.
What did they find? Why is this important?
1. In general, not enough lymph nodes are being assessed in North American patients who have surgery for gastric cancer.
2. The average number of lymph nodes assessed is different around the world. However, fewer LN are being assessed on average in North America compared to other parts of the world (like East Asia).
3. The use of the D2 lymphadenectomy surgical technique is also different around the world because there is not yet an international standard of treatment.
4. New research is showing that chemotherapy can help reduce the problem of lymph nodes becoming cancerous and can improve survival.

How many lymph nodes should be assessed in patients with gastric cancer? A systematic review (2011)

https://www.researchgate.net/publication/230678433_How_many_lymph_nodes_should_be_assessed_in_patients_with_gastric_cancer_A_systematic_review

Seevaratnam, Rajini, et al. “How many lymph nodes should be assessed in patients with gastric cancer? A systematic review.” Gastric Cancer 15.1 (2012): 70-88. Available from: doi: 10.1007/s10120-012-0169-y
What question is this study asking?
1. In East Asian countries, doctors tend to do D2 lymphadenectomies in gastric cancer surgery. In North America, doctors are more likely to do a D1 lymphadenectomy instead.
2. This study wanted to learn about how assessing more (in D2) or fewer (in D1) lymph nodes might affect the results of a surgical procedure.
How did they address this question?
1. The paper analyzed 25 different studies from seven different countries around the world.
What did they find? Why is this important?
1. Patients whose tumors were more advanced (based on size and TNM stage) tended to have more lymph nodes removed by their surgeons.
2. These patients who had more LN assessed lived longer overall without cancer after surgery. The authors hypothesized that these patients are simply receiving better healthcare in general, which is maybe why they live longer.
3. To fix this problem and make sure that all patients have the best chances of surviving, this paper recommends that in North America, 25 LN are assessed during gastrectomy.
4. This is very important because gastric cancer in North America is often diagnosed at an advanced stage. So, removing and assessing more LN will make it more likely that surgeons can get rid of all of the cancer cells and better treat the patient.

What is the accuracy of sentinel lymph node biopsy for gastric cancer? A systematic review (2012)

https://www.ncbi.nlm.nih.gov/pubmed/22262403

Cardoso, Roberta, et al. “What is the accuracy of sentinel lymph node biopsy for gastric cancer? A systematic review.” Gastric cancer 15.1 (2012): 48-59. Available from: doi: 10.1007/s10120-011-0103-8.
What is this study trying to learn?
1. The first LN in a chain is called the sentinel lymph node. When cancer moves to the sentinel lymph nodes, there is a good chance that it will spread to the other LN too.
2. Identifying sentinel lymph nodes can be helpful to remove the cancer from the LN system before it spreads too far. This information can also tell a surgeon how extensive a patient’s surgery needs to be.
3. This study looked at the accuracy of different methods of determining if a sentinel lymph node had cancer. It was also interested to know how this might affect a gastric cancer patient’s treatment.
How did the study address this question?
1. This review included n=26 articles from around the world.
2. They compared 3 main methods of assessing sentinel lymph nodes. These were:
  1. dye method (DM)
  2. radiocolloid method (RM)
  3. dye + radiocolloid method (DUAL).
3. All three of these methods involve injecting different chemicals into the body which can be traced temporarily. This helps a doctor create a map of LNs and how they are connected.
4. The most important factor to consider when determining the usefulness of a particular method is its false-negative rate.
5. The false-negative rate in this study is the proportion of times that the test says an sentinel lymph nodes is not cancerous, when it actually is.
6. A testing method with a high false negative rate is not very accurate. This means it fails to detect a lot of cancerous sentinel lymph nodes. So, it would not give the surgeon a very good understanding of where the cancer cells are.
What did they find? Why is this important?
1. This paper concluded that of the three methods, DUAL seemed to have a slightly improved false negative rate.
2. They also found that identifying sentinel lymph nodes is not very impactful on patient outcomes in early gastric cancer.
3. But, it can provide helpful information when used correctly in advanced gastric cancer patients.

A meta-analysis of D1 versus D2 lymph node dissection (2012)

https://www.ncbi.nlm.nih.gov/books/NBK127357/

Seevaratnam, Rajini, et al. “A meta-analysis of D1 versus D2 lymph node dissection.” Gastric Cancer 15.1 (2012): 60-69. Available from: 10.1007/s10120-011-0110-9
What is this study trying to learn?
1. There is not yet a standard way for a surgeon to decide whether to do a D1 or D2 lymphadenectomy.
2. This paper tried to figure out if D1 or D2 lymphadenectomy is safer and/or more helpful.
How did they address this question?
1. This paper reviewed 5 important experiments involving 1,642 patients.
What did they find? Why is this important?
1. Short term results after surgery were similar for most D1 and D2 patients.
2. However, if patients had advanced gastric cancer (with a T3/T4 tumor) or their surgery involved removing organs other than the stomach and lymph nodes (such as the spleen and pancreas), then the D2 method was worse.
3. They also found that in recent years, the results of D2 surgeries have been better for patients than they were in the past. This shows that patient health is improving over time as a result of new research and surgical practice!
4. Conclusion + applications: It is still hard to know if D1 or D2 is better. The authors of this paper think that learning about the long-term effects of some of the studies they analyzed will give more information to make this decision.
5. For example, it could be useful to know how long patients live without having a relapse of cancer after a D1 or D2 surgery. But unfortunately, this has not been researched extensively yet. Perhaps in the future more information will become available.