Current medicine is heavily relying on newer technologies to aid in diagnosing and treating difficult medical conditions. This is especially so in the cases of cancers such as breast cancer. Breast cancer claims thousands of lives each year, many of which are preventable with early diagnosis and treatment. Therefore a diagnostic procedure that is able to do just that can be a boon to the health care provider. The introduction of the sentinel node biopsy procedure in breast cancer diagnostics and oncology is one of the most claimed victories against cancer, as it is able to diagnose primary stages of cancers as early as T1 and N0 phases. Also, the procedure is able to conserve much of the healthy breast tissue, and removes the need for entire axillary lymph nodes removal. However, as reported by Gemignani et al in 2000, in T1 cases, there remains a 10% chance that a patient may need to have the axillary lymph nodes removed after all. (Gemignani et al, 2000) Many researches have been able to demonstrate high success rates of detection in both new as well as already operated cases of breast cancer. (Eary, 1999)
The procedure however, is very detail oriented as it primarily deals with the use of radioactive isotopes. Therefore, proper knowledge about the material and the technique and proper case selection is of utmost importance. Sentinel node biopsy has found its place not only in diagnostics, but also in surgeries and post operative assessments as well. Although there is still a limited number of trials that can claim the procedure to be safe, its efficacy has led to widespread use of the procedure in many routine breast cancer investigations.
This procedure involves the nuclear medicine department as much as the surgeon himself, and therefore, proper coordination between the two parties is essential. Further importance lies in justifying the need for sentinel node biopsy in a particular case, and addressing the dosage schedule of the material being injected. Cases such as those of pregnancy will warrant more attention. (Morton et al, 2003)
The concept behind sentinel lymph node biopsy is not new and the procedure is basically a revival of a long known concept. This procedure, also known as the lymphoscintigraphy, is the fusion of two techniques of lymph mappings carried out before surgeries, and the gamma probe detection method that is carried out during surgery. (Jansen et al, 1999) This along with high reproducibility rates has made the procedure a hot favorite among the surgeons.
Many factors for successful sentinel node biopsy have been demonstrated through various trials. Intradermal technique of injection has been found to be more successful than intraparenchymal injections. Similarly, a positive lymphoscintigraphy very nearly ensures sentinel lymph node location by the isotope. The use of blue dye has been more productive in outer quadrant tumors, but this is only if blue dye is used in isolation. If both blue dye and isotope is used in conjunction, the rates of successful detection remain the same. It has been found to be more successful in cases that have had some previous surgical biopsy procedure, than a concurrent one. Sentinel node detection is better in younger age groups than in older cases above the ages of 60, and becomes better when dual method is used. (Fey et al, 2001) These and many such findings are making surgeons better understand various techniques that can improve sentinel node outcomes.
Currently, the dyes used in sentinel node biopsy are broadly categorized into two types. The first is the blue dye called patent blue or isosulfan blue and the second is the introduction of radioactive substances and isotopes such as 99Tcm-Nanocoll , 99mTc-antimony trisulfide or 99mTc-sulfur colloid. The methodology for using these tracers is different, for example the isotopes are used prior to surgery and are injected around the tumor. This then is detected by the gamma probe, and later on the blue dye is injected to better aid in visualization and location of the nodes. (Tsopelas and Sutton, 2002) The injection technique used for this procedure is essentially separate injections for both dyes, but with the introduction of naphthol azo dyes and Evans blue dye, both can be injected simultaneously. It is important that the dye injected, be it a radiotracer or blue dye, must be able to attach itself and express itself within the lymph. This is difficult as the protein binding within lymph is lesser when compared to blood or plasma. Each dye currently used in sentinel procedures has its unique characteristics. For example, isosulfan blue is able to stain the lymph nodes better than other dyes such as methylene blue. This localization is enhanced particularly if nodes are undetectable in cases if Evan blue dye is incorporated simultaneously. Isosulface dye is able to traverse itself in the lymphatics rapidly, and for this reason, it is better to inject it just prior to surgery. The many dyes that have been investigated for rapid binding in the lymph include acid yellow 42, naphthol blue black, nitrazine yellow, chrysophenine, direct yellow 27 and reactive blue 4. Other stains include Evans blue and Chicago sky blue, with highest binding capacities in the lymph. (Tsopelas and Sutton, 2002)
Most of these dyes are excreted out through the urine by entering in to the blood stream, and it is therefore, the urine stains blue to green colored in 18 hours after surgery. (Tsopelas and Sutton, 2002)
It should be clarified that the patient is not allergic to any of the tracer substance that is injected in to her, as agents such as isosulfan blue can cause severe hypersensitivity reactions. These may present as hypotension, tachycardia, dysrhythmias, cardiac arrest, urticaria, flushing and respiratory failure. (Dean and Weinholz, 2000)
There is much debate about the method of tracer injection in to the body in breast cancer cases. Each method has its own advantages and set backs. For example, if the subdermal route is opted, the lymph nodes in the axilla can be almost fully visualized, but almost opposite occurs for lymph node drainages outside of the axilla. (Jansen et al, 1999) Some what better visualization of the extra axillary lymph nodes is seen when perimoural and intramoural methods are carried out.(Jansen et al, 1999)
Similarly, the kind of technique of injection can also govern how and when the gamma rays will pick up the lymph nodes. Subdermal and intramoural injection of the tracer leads to early detection of the lymph nodes. The initial injection is placed at four points around the tumors site where the lymph nodes and their drainage is ascertained via lymphoscintigraphy method. The method identifies, locates and thereby fixes the position of the nodes, which are later on helpful in the surgery procedure to aid in removal. The sentinel nodes are recognized due to their high radiotracer uptake through the gamma probe, which are then subsequently removed.
Most of the radiotracer procedures must be carried out in the nuclear medicine department as it ensures that the staff is well prepared for the management of such materials. In surgery, the surgeon operating along with his staff must know the necessary methods to avoid exposure to such materials and how to seal and contain them. (Morton et al, 2003) Due to the risk of exposure to radiation, it is strongly advised that surgeries be performed on the same day that the radiotracer is introduced in the body. (Morton et al, 2003)
Visualization of these nodes is usually carried out with the patient in a supine position. The imaging is carried out immediately after the injection of the blue dye and around 2 to 3 hours after the injection of the radiotracer. Flood sources can also be used in order to help delineate the body outline and thereby assist in the visualization of the nodes. The sentinel nodes with the help of imaging are given a reference point by marking on the skin. Mostly the flooding and positioning are achieved via the help from Cobalt- 57 and other such materials. (Morton et al, 2003)
Many issues can make visualization of the lymph nodes difficult. Breast’s afferent lymph nodes drain slower than most other tissues, and this can affect the both the interpretation of the data and creating diagnosis. Also, in some of the cases, the concurrent or subsequent use of the blue dye may be necessary to reach a definite conclusion in a case. (Jansen et al, 1999)
Nonvisualization of the sentinel nodes is therefore an area of chief concern among surgeons, raise questions about the true efficacy of the treatment. Many factors are thought to contribute to the non visualization of the nodes and may include the type of agent used in the imaging and the type of image guidance used the radioactive counts in vivo, the need for lymphoscintigraphy and the time at which it is carried out, and the histological status of the sample. (Rousseau et al, 2004) Rousseau et al (2004) claims a statistical relation between “negative lymphoscintigraphy, unsuccessful axillary mapping, and a high number of metastasis in axillary nodes.” (Rousseau et al, 2004) Tracer factors can include the size of the particles and their route of administration. Increasing the concentration of the label in the injection is thought to increase its retention and therefore detection within the lymph nodes. Similarly, the subdermal areolar method of administration with in the breast tissue has shown improved visualization. Too many surgeons therefore, understanding the anatomical variations and the chemistry of various radiotracers is important in the successful visualization. Also, the surgeons believe that the conduction of preoperative lymphoscitigraphy can in fact be beneficial and may increase likelihood of successful detection of sentinel nodes. (Rousseau et al, 2005)
The exposure to radioisotopes is not only a matter of concern to the patient but also to those who are in contact with it in during and after surgery.
The removal of the lymph nodes is carried out prior to any other radical procedure such as lumpectomy or mastectomy. This is to allow the lymph nodes to remain patent even after surgery, thereby enhancing the post surgical outcomes. The dye is also able to stay with in the lymph nodes, which is of help during and after surgery.
Any material that is excised is sent to histopathology for further investigations. This sample is first radio graphed to check the integrity of the specimen margins. This is usually carried out during the surgery so as to ensure no cancerous tissue in the area remains. The axillary lymph nodes if found to have sentinel nodes are dealt with the same way.
The use of gamma probe is carried out to detect the nodes that are stained with radioisotope and thereby identify the sentinel nodes. This method is used widely in the procedure, however, there are reports that gamma probing may lead to over identification of “more nodes than necessary”. (Cserni et al, 2000) Although this may occur, there is insufficient knowledge about why this would be the case. Factors thought to contribute to it may include the size and the type of colloid used and the injection technique etc. This remains an issue of further investigation and discussion, however, the use is primarily due to the fact that gamma probes are better able to identify sentinel nodes accurately than any other method available. (Cserni et al, 2000) The high costs of these gamma probes may make this procedure rare in poor countries.
Concerns about the dosage of the radioactive materials introduced within a pregnant patient with breast cancer and the effects on the fetus have also been investigated. Tasker and her colleagues’ study in 2006 aimed to quantify the dose with which the fetus may be exposed due to SLB procedure, and concluded that this amounts to 0.014 mGy or less, which is well below the limit set for pregnant women in the National Council on Radiation Protection and Measurements. Thus the sentinel node biopsy procedure can be considered a safe procedure to be carried out on a pregnant patient. (Tasker et al, 2006)
In conclusion, the introduction of sentinel node biopsy is becoming front line methods for early detection of breast cancers, and to help decrease morbidity in such cases. The results of the many studies conducted so far have shown very good responses and the use of radioisotopes have been found to be safe and under limits. The efficacy of this procedure will continue to grow as more and more methods, techniques and studies will come to light.
REFERENCES
Dean Susan F and Weinholz Sandra, 2000. Sentinel Lymph Node Dissection as a Means of Managing Breast Cancer. AORN Journal 72, Oct 2000, 633-638
Gábor Cserni, Mária Rajtár and Gábor Boross Blue Nodes Left Behind After Vital Blue Dye-guided Axillary Sentinel Node Biopsy in Breast Cancer Patients Japanese Journal of Clinical Oncology 30:263-266 (2000)
Janet F. Eary, David A. Mankoff, Lisa K. Dunnwald, David R. Byrd, Benjamin O. Anderson, Raymond S. Yeung, and Roger E. Moe, 1999. Sentinel Lymph Node Mapping for Breast Cancer: Analysis in a Diverse Patient Group Radiology. 1999;213:526-529.
Hiram S. Cody III, Jane Fey, Tim Akhurst, Melissa Fazzari, PhD, Madhu Mazumdar, Henry Yeung, Samuel D.J. Yeh, and Patrick I. Borgen, 2001. Complementarity of Blue Dye and Isotope in Sentinel Node Localization for Breast Cancer: Univariate and Multivariate Analysis of 966 Procedures Annals of Surgical Oncology 8:13-19 (2001)
Gemignani, M. L., Cody H. S. 3rd, Fey J. V., Tran K. N., Venkatraman E. and Borgen P. I., 2000. Impact of Sentinel Node Mapping on Relative Charges in Patients with Early Stage Breast Cancer. Annals of Surgical Oncology, Vol. 7 Issue 8, 575-580.
Jansen L., Valdes Olmos RA, Muller SH, Hoefnagel CA and Neiweg O, 1999. Contribution of Nuclear Medicine to Lymphatic Mapping and Sentinel Node Identification in Oncology. Revista Espanola de Medicina Nuclear 1999; 18(2):111-121
Morton R., Horton PW, Peet D J, Kissin M W, Chir M, 2003. Quantitative Assessment of the Radiation Hazards and Risks in Sentinel Node Procedures. British Journal of Radiology (2003) 76, 117-122
Pandit-Tasker Neeta, Dauer Lawrence T., Montgomery Leslie, Germain Jean St., Zanzonico Pat B. and Divgi Chaitanya R. Organ and Fetal Absorbed Dose Estimates from 99mTc-Sulfur Colloid Lymphoscintigraphy and Sentinel Node Localization in Breast Cancer Patients, 2006. Journal of Nuclear Medicine Vol. 47 No. 7 1202-1208
Rousseau C, Classe J M, Campion L, Curtet C, Dravet F, Pioud R, Sagan C, Bridji B, and Resche I, 2005. The Impact of Non Visualization of Sentinel Nodes on Lymphoscintigraphy in Breast Cancer. Annals of Surgical Oncology 12:533-538 (2005)
Tsopelas Chris and Sutton Richard, 2002. Why Certain Dyes are Useful for Localizing the Sentinel Lymph Node. Journal of Nuclear Medicine Vol 43, No. 10, 1377-1382.
