Lymphatic mapping and sentinel lymph node biopsies

Once melanoma cells leave the skin and travel to the lymph nodes, they have metastasized, thereby reducing chances for the patient's long-term, disease-free survival. Methods for tracing and removing lymph nodes include elective lymph node dissection, lymphoscintigraphy, and sentinel lymph node biopsy. This article reviews the concepts, procedures, and effectiveness of these techniques.     

Lymphatic mapping and sentinel node biopsy in gastric cancer

BACKGROUND: To determine the feasibility and significance of lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with gastric cancer. METHODS: From August 1999 to January 2002, 27 gastric cancer patients underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye. RESULTS: The success rate of SLNB was 96.3% (26 of 27). Accuracy, sensitivity, and specificity were 100%. There were no false negatives. In 26 successful cases, 8 patients had positive sentinel lymph nodes and 18 had negative sentinel nodes. Of 8 patients with positive sentinel nodes, 6 had positive sentinel nodes only at N1 lymph node station, 1 only at N2 station, and 1 had positive sentinel nodes at both N1 and N2 stations. Of 18 patients with negative sentinel lymph nodes, 9 patients had sentinel nodes only at N1, 3 only at N2, 5 at both N1 and N2, and 1 at both N1 and N3. There were no cases in which sentinel lymph nodes were the only sites of metastases. CONCLUSIONS: Sentinel lymph node biopsy using isosulfan blue dye in gastric cancer is a feasible procedure with high sensitivity and accuracy. Sentinel lymph nodes demonstrate the varied lymphatic drainage. If the sentinel nodes at N2 are positive, it will guide surgeons to do a more extended lymph node dissection in early stage gastric cancer.     

Timing of sentinel lymph node mapping after lymphoscintigraphy.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective technique for staging patients with melanoma. In an attempt to avoid reinjection of radiolabeled colloid and facilitate SLN mapping at the time of surgery, we examined whether residual radioactivity from preoperative lymphoscintigraphy could be used to accurately identify SLNs during surgery 18 to 24 hours later. METHODS: Forty-six patients with newly diagnosed melanoma underwent injection of 0.22-micron filtered technetium 99m-labeled sulfur colloid followed by lymphoscintigraphy. Patients returned the next day for SLN biopsy with Isosulfan blue dye and the hand-held gamma-probe to identify SLNs. Thirty of 46 patients underwent repeat imaging before operation. No patient had reinjection of radiocolloid. RESULTS: Ninety-five SLNs were identified on initial lymphoscintigraphy, and repeat imaging on the day of surgery confirmed all SLNs previously identified. A total of 122 SLNs (2.65 per patient) were resected from 58 basins. Eighty-four (69%) of 122 SLNs stained blue, and 118 (97%) of 122 SLNs had in vivo gamma-counts greater than 4 times background. Microscopic metastases were present in 13 (10.7%) of 122 SLNs in 12 (26.1%) of 46 patients. There have been no recurrences over a mean follow-up time of 320 days. CONCLUSIONS: Intraoperative gamma-probe detection combined with blue dye injection is highly effective in identifying SLNs 18 to 24 hours after injection of 0.22-micron filtered 99mTc-sulfur colloid. Reinjection of radiocolloid is not required. This technique avoids radiopharmaceutical administration in the operating room, minimizes radiation exposure, and increases scheduling flexibility.     

Lymphatic mapping with sentinel node biopsy in pediatric patients

BACKGROUND/PURPOSE: Lymphatic mapping with sentinel node biopsy is used widely in adult melanoma and breast cancer to determine nodal status without the morbidity associated with elective lymph node dissection. This technique can be used in children to determine lymph node status with limited dissection and accurate interpretation. The authors report their initial experience. METHODS: The charts of patients who underwent lymphatic mapping with sentinel node biopsy were reviewed retrospectively. Lymphoscintigraphy was performed in patients with truncal lesions 24 hours before surgery to determine the draining nodal basin (for surgical mapping). The tumors were injected 1 hour preoperatively with technetium sulfur colloid and in the operating room with Lymphazurin blue. The draining basin was examined using a radioisotope detector. The blue nodes with high counts were localized and removed. If nodal metastases were identified, lymph node dissection was recommended. Four patients were injected only with Lymphazurin blue. RESULTS: Thirteen children (7 girls, 6 boys; mean age, 7 years) underwent lymphatic mapping with sentinel node biopsy. The tumor types were as follows: 8 malignant melanoma (6 extremity, 2 truncal), 1 malignant peripheral nerve sheath tumor, 1 alveolar soft part sarcoma, and 3 rhabdomyosarcoma. A mean of 2.4 nodes (range, 1 to 6) were removed from each patient. Six patients had a positive sentinel node. Formal lymph node dissection was performed on 4 of the 6 patients, 1 of whom had further nodal disease with 2 of 13 nodes containing micrometastases. One of the 6 patients refused lymph node dissection and adjuvant therapy; the final patient had rhabdomyosarcoma, a malignancy for which lymph node dissection is not indicated. Pulmonary metastasis developed 26 months after diagnoses in the patient with alveolar soft part sarcoma and a negative sentinel node. This patient was injected only with Lymphazurin blue at the time of sentinel node biopsy and refused adjuvant therapy. There have been no other recurrences. There were no complications related to lymphatic mapping or sentinel node biopsy. CONCLUSIONS: Lymphatic mapping with sentinel node biopsy, using both technetium-labeled sulfur colloid and Lymphazurin blue, can be performed safely in pediatric skin and soft tissue malignancies. Further study with long-term follow-up will determine the utility and accuracy of this technique in pediatric malignancies.     

Lymphatic mapping techniques and sentinel lymph node biopsy in breast cancer

The axillary nodal status is accepted universally as the most powerful prognostic tool available for early stage breast cancer. The removal of level I and level II lymph nodes at axillary node dissection (ALND) is the most accurate method to assess nodal status, and it is the universal standard; however, it is associated with several adverse long-term sequelae. Lymphatic mapping with sentinel lymph node biopsy has emerged as an effective and safe alternative to the ALND for detecting axillary metastases. This article discusses some lymphatic mapping methodology.     

Lymphatic mapping and sentinel node biopsy during laparoscopic gastrectomy for early cancer

BACKGROUND/AIMS: Intraoperative lymphatic mapping and sentinel node (SN) biopsy can potentially be combined with minimally invasive surgery, but there are few reports of laparoscopic lymphatic mapping for gastrointestinal cancer. We examined the feasibility and accuracy of laparoscopic lymphatic mapping in predicting lymph node status in patients with gastric cancer. METHODS: Seventeen patients with gastric cancer invading the mucosal or submucosal layers (T1) underwent laparoscopic gastrectomy with lymphatic mapping between March 2001 and May 2002. The day before surgery, a technetium-99m-labelled tin colloid solution was injected endoscopically around the tumor. Immediately after the pneumoperitoneum, patent blue was injected. Gastrectomy was performed in all patients, and blue-stained or radioactive nodes were defined as SNs. Fresh SNs were immediately processed for frozen-section examination by hematoxylin-eosin (H and E) and immunohistochemical (IHC) staining. All non-SNs harvested from resected specimens were subjected to histological examination with H and E. RESULTS: SNs were detected in all patients by combination of the two kinds of tracers. Three patients had lymph node metastases in their final examination, and SNs in these 3 were operatively diagnosed as positive by H and E or IHC staining. Lymphatic mapping and SN biopsy under laparoscopic surgery were performed with 100% accuracy. CONCLUSION: Our preliminary study shows the feasibility of intraoperative lymphatic mapping in laparoscopic gastrectomy for T1 gastric cancer.     

Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathological correlation

PURPOSE: We assessed the sensitivity of preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging the inguinal region of patients with penile cancer and no palpable inguinal adenopathy. MATERIALS AND METHODS: The records of 31 patients with invasive penile cancer and nonpalpable (29) or nonsuspicious (2) inguinal lymph nodes were reviewed. Preoperatively lymphoscintigraphy plus dynamic sentinel node biopsy with (99m)technetium labeled sulfur colloid and isosulfan blue dye was performed in 21 patients and dynamic sentinel node biopsy alone with blue dye only was done in 10. All patients underwent superficial lymph node dissection regardless of preoperative lymphoscintigraphy or dynamic sentinel node biopsy findings to establish pathological nodal status. RESULTS: Six of 32 groins that showed drainage on preoperative lymphoscintigraphy had inguinal node metastasis, as did 1 of 10 that was drainage negative. The sensitivity of preoperative lymphoscintigraphy drainage for cancer detection was 86%. Using dynamic sentinel node biopsy with blue dye plus radiotracer 5 sentinel lymph nodes were positive for cancer, although 2 false-negative results were obtained. Thus, the sensitivity of dynamic sentinel node biopsy per groin for cancer detection was 71%. CONCLUSIONS: In our experience preoperative lymphoscintigraphy and dynamic sentinel node biopsy as currently performed remain insufficient for detecting occult inguinal disease. Superficial lymph node dissection remains the gold standard for detecting inguinal microscopic metastasis in select patients.     

Lymphatic mapping and sentinel lymphadenectomy for breast cancer

Lymphatic mapping and sentinel lymphadenectomy has become an important tool for axillary lymph node staging in women with early-stage breast cancer. This review examines data regarding the staging accuracy, indications and technical aspects of the procedure, and clinical trials investigating the technique. Multiple studies now confirm that sentinel lymphadenectomy accurately stages the axilla and is associated with less morbidity than axillary dissection. Blue dye, radiocolloid, or both can be used to identify the sentinel node, and several injection techniques may be used successfully. Many patient factors previously thought to affect accuracy of the procedure have now been shown to be of limited significance. The indications for the procedure are expanding, and the histopathologic evaluation of the sentinel node and the role of lymphoscintigraphy have been clarified. Clinical trials are now underway that will determine the prognostic significance of micrometastases and the therapeutic benefit of axillary dissection in women with and without sentinel node metastases. Incorporation of sentinel lymphadenectomy into routine clinical practice will maintain accurate axillary staging with lower morbidity and improved quality of life for women with early-stage breast cancer.     

Lymphatic drainage patterns of head and neck cutaneous melanoma observed on lymphoscintigraphy and sentinel lymph node biopsy

BACKGROUND: The purpose of this study was to evaluate lymphatic drainage patterns of head and neck cutaneous melanoma observed on preoperative lymphoscintigraphy and sentinel lymph node biopsy (SLNB) and determine discordancy from clinically predicted lymphatic drainage patterns. METHODS: We conducted a retrospective chart review of 114 patients with head and neck cutaneous melanomas evaluated with preoperative lymphoscintigraphy and SLNB from January 2001 through July 2004. RESULTS: At least one sentinel lymph node (SLN) was identified in 97% of cases. On preoperative lymphoscintigraphy, an SLN was identified in an area not clinically predicted in 49 cases (43%). The most common sites of discordancy were in areas not typically dissected in standard neck dissections, such as the postauricular region, or in areas of more distant drainage than described previously, such as the inferior or posterior neck. Their percentages of discordant cases were 51%, 27%, and 22%, respectively. The sites of regional recurrence occurred in two cases not predicted on preoperative lymphoscintigraphy and in two cases of failed SLNB. CONCLUSIONS: On the basis of preoperative lymphoscintigraphy and the results of SLNB, head and neck cutaneous melanomas do have expected lymphatic drainage patterns despite perceived discordancy with previously clinically predicted drainage patterns that are based on standard neck dissection specimens. These "discordant" sites can still harbor melanoma, and all sites predicted on preoperative lymphoscintigraphy still need to be explored. The four cases of recurrences underscore the importance of close follow-up for all patients regardless of the SLNB result.     

Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer

Background: Lymphoscintigraphy and sentinel node biopsy are currently being assessed as an alternative to axillary dissection for staging in early breast cancer. However, little is known about the optimum timing of surgery following injection of the radio­isotope into the breast. The aim of the present study was to establish whether lymphoscintigraphy on the morning of surgery allowed efficacious and accurate sentinel node identification and biopsy. Methods: We reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early breast cancer using peritumoural injections of technetium^99m antimony sulphide colloid and subsequent sentinel node biopsy using a hand‐held gamma probe and blue dye. The time interval between radioisotope injection and successful intraoperative identification of the sentinel node was assessed and whether this was associated with certain clinical and histological variables. Results: The sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median time duration of 40 min post injection. The median time duration between isotope injection and surgery was 5 h. Of the 160 cases where the sentinel node was visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy failed to localize the sentinel node (P < 0.0001). There was no association found between the injection of the radioisotope greater or less than 5 h before surgery and the successful intraoperative identification of the sentinel node. Failure to identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a low intraoperative identification rate. There was no correlation found between intraoperative identification of the sentinel node according to the duration of isotope injection in relation to surgery and the various clinical and histological factors assessed. Conclusions: In our experience, the chance of identifying the sentinel node at the time of surgery does not increase with longer isotope injection duration using technetium^99m antimony sulphide colloid. As soon as a sentinel node is identified at lymphoscintig­raphy, one can proceed to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node localization. Given that the median time for successful lymphoscintigraphic mapping was only 40 min, lymphoscintigraphy can easily be completed during the morning to allow surgery to take place the same day.     

Lymphatic mapping and sentinel node biopsy using 99mTc tin colloid in gastric cancer

OBJECTIVE: The aim of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy in patients with gastric cancer for the assessment of regional lymph node status. SUMMARY BACKGROUND DATA: SLN is the first draining node from the primary lesion, and it is the first site of lymph node metastasis in malignancy. SLN mapping and biopsy are of great significance in the determination of the extent of lymphadenectomy, allowing patients with gastric cancer to have a better quality of life without jeopardizing survival. METHODS: The SLN biopsy was performed in 46 consecutive patients having gastric cancer with a preoperative imaging stage of T1/T2, N0, or M0. Three hours prior to each operation, Tc tin colloid (2.0 mL, 1.0 mCi) was endoscopically injected into the gastric submucosa around the primary tumor. Subsequently, serial lymphoscintigraphy was performed using a dual-head gamma camera. After the SLN biopsy had been performed using a gamma probe, all patients underwent radical gastrectomy (D2 or D2+alpha). The SLN was cut and immediately frozen-sectioned. A paraffin block was then produced for permanent hematoxylin-eosin staining and immunohistochemistry (IHC). RESULTS: SLNs were successfully identified in 43 of 46 patients (success rate, 93.5%). On average, 2 (range, 1-8) SLNs were identified per patient. The positive predictive value, negative predictive value, sensitivity, and specificity of SLN biopsy were 100% (11 of 11), 93.8% (30 of 32), 84.6% (11 of 13), and 100% (30 of 30), respectively. SLNs were located at the level I lymph nodes in 38 (88.4%), the level I+II nodes in 2 (4.7%), and the level II nodes in 3 (7.0%). No micrometastases of SLNs was found on IHC for cytokeratin. CONCLUSIONS: SLN biopsy using a radioisotope in patients with gastric cancer is a technically feasible and accurate technique, and it is a minimally invasive approach in the assessment of patient nodal status.     

Lymphatic mapping and sentinel node biopsy in penis cancer. Feasibility study and preliminary report

Most patients with invasive squamous cell carcinoma of the penis do not have inguinal node metastasis at the time of diagnosis and 50% of those having palpable nodes are inflammatory. Penis cancer (PC) treatment implies resection of the primary tumor and inguinal lymphadenectomy; nevertheless, morbidity related to this procedure is high and its usefulness may be questioned in patients without metastasis in dissected nodes. Lymphatic mapping with sentinel node biopsy (LMSNB) is a valid alternative, useful in other neoplasias. The objective of this study is to determine if it is possible to identify a sentinel node (SN) in patients with PC. Patients with T1-2 PC without palpable nodes (N0) were included. LMSNB was carried out with the combined technique (blue dye and radiocolloid). All patients underwent an elective bilateral inguinal lymphadenectomy. Sensitivity and false negative index were calculated. SNs were sent for transoperative study with imprint technique and, definitively, with serial cuts and hematoxylin/eosin staining. Nine patients showed results with 32 lymph carrier zones and SN was identified in all of them, 4 regions had metastasis, in 3 the SN was metastatic and in one patient was metastasis-negative (false negative); sensitivity = 80%; false negatives index = 20%. Seven patients (77%) did not have node metastasis. LMSNB is an alternative for staging PC patients and could prevent unnecessary inguinal lymphadenectomies. A larger number of patients is required to validate the sturdy. The combined technique offers a high rate of success in SN identification.     

Lymphatic mapping and sentinel lymphadenectomy for breast cancer.

OBJECTIVE: The authors report the feasibility and accuracy of intraoperative lymphatic mapping with sentinel lymphadenectomy in patients with breast cancer. SUMMARY BACKGROUND DATA: Axillary lymph node dissection (ALND) for breast cancer generally is accepted for its staging and prognostic value, but the extent of dissection remains controversial. Blind lymph node sampling or level I dissection may miss some nodal metastases, but ALND may result in lymphedema. In melanoma, intraoperative lymph node mapping with sentinel lymphadenectomy is an effective and minimally invasive alternative to ALND for identifying nodes containing metastases. METHODS: One hundred seventy-four mapping procedures were performed using a vital dye injected at the primary breast cancer site. Axillary lymphatics were identified and followed to the first ("sentinel") node, which was selectively excised before ALND. RESULTS: Sentinel nodes were identified in 114 of 174 (65.5%) procedures and accurately predicted axillary nodal status in 109 of 114 (95.6%) cases. There was a definite learning curve, and all false-negative sentinel nodes occurred in the first part of the study; sentinel nodes identified in the last 87 procedures were 100% predictive. In 16 of 42 (38.0%) clinically negative/pathologically positive axillae, the sentinel node was the only tumor-involved lymph node identified. The anatomic location of the sentinel node was examined in the 54 most recent procedures; ten cases had only level II nodal metastases that could have been missed by sampling or low (level I) axillary dissection. CONCLUSIONS: This experience indicates that intraoperative lymphatic mapping can accurately identify the sentinel node--i.e., the axillary lymph node most likely to contain breast cancer metastases--in some patients. The technique could enhance staging accuracy and, with further refinements and experience, might alter the role of ALND.     

Reproducibility of lymphoscintigraphy for lymphatic mapping in patients with penile carcinoma

PURPOSE: We evaluated the reproducibility of lymphoscintigraphy in the assessment of the location and number of sentinel nodes in patients with penile carcinoma. MATERIALS AND METHODS: A total of 20 patients were prospectively included in analysis. Lymphoscintigraphy was performed after intradermal injection of technetium nanocolloid around the tumor or excision scar. We performed 10-minute anterior dynamic imaging, and static anterior and lateral images were obtained at 30 minutes and 2 hours. The following day scintigraphy was repeated after a second injection of the radiolabeled colloid given in an identical fashion, preceded by acquisition of a starting image. An observer evaluated the paired images and count rates were calculated from the images. RESULTS: At least 1 sentinel node was visualized in all patients on the first lymphoscintigram. A total of 56 sentinel nodes were seen in 38 basins. Drainage to both groins was seen in 18 patients. In 1 of these patients drainage to the prepubic area was also observed. There were 2 patients with drainage to 1 groin. The second lymphoscintigram revealed the same drainage pattern in all patients- the same number of nodal basins and number of sentinel nodes were visualized at identical locations. All hotspots that were visualized during the first lymphoscintigram showed an unequivocal increase in radioactivity after repeat injection. Thus, the reproducibility of penile lymphoscintigraphy was 100% (95% CI 85%-100%). The Pearson correlation coefficient of the paired count rates was 0.69 (p <0.0001). CONCLUSIONS: Results of lymphoscintigraphy in patients with penile carcinoma are highly reproducible for assessment of the number and location of sentinel nodes.     

Pre-operative lymphoscintigraphy before sentinel lymph node biopsy for breast cancer

Pre-operative lymphoscintigram for axillary sentinel lymph node biopsy (SLNB) may not be required for successful SLNB. The 117 consecutive patients who underwent SLNB had pre-operative lymphoscintigraphy. The operating surgeon was blinded to the results of the lymphoscintigram before SLNB. After SLNB was complete, the surgeon was unblinded to the results of the lymphoscintigram; re-exploration carried out if more nodes were predicted on the lymphoscintigram. 116 patients (99%) had successful SLNB before unblinding. In 85 patients (73%), operative findings corresponded with scintigraphic findings. In 26 patients (22%), the lymphoscintigram predicted more sentinel nodes than had been found; further nodes were identified and excised in only 4 patients (3%). None were positive for cancer. SLNB was successful in 99% of cases without pre-operative lymphoscintigraphy. Only 3% of patients had further nodes identified as a result of the lymphoscintigram. Pre-operative lymphoscintigraphy does not improve the ability to perform axillary SLNB during breast cancer surgery.     

Preoperative lymphoscintigraphy and internal mammary sentinel lymph node biopsy do not enhance the accuracy of lymphatic mapping for breast cancer

Lymphoscintigraphy (LS) may identify sentinel lymph nodes (SLNs) outside the axilla. Biopsy of these nodes could improve the accuracy of lymphatic mapping (LM) for breast cancer (BC) if a significant number of tumor-positive extra-axillary sentinel nodes are identified. To address this, we evaluated the impact of the use of preoperative LS and biopsy of axillary and internal mammary SLNs in women with BC. From October 1997 to July 2003, 175 women with breast cancer received technetium sulfur colloid, and images were obtained. Isosulfan blue dye was injected intraoperatively, and LM of the axillary and internal mammary lymph node basins was performed with a hand-held gamma probe. The anatomic location and histologic status of all SLNs identified with LS and LM was recorded, and the impact of the findings on LS and internal mammary LM were evaluated. LS showed SLN in 127/175 (73%) women and "hot spots" were found with the gamma probe in 142/175 (81%). At least one SLN was identified by LM in 168/175 (96%) patients, and 48/168 (29%) had metastases. One hundred sixty-two of 168 (96%) patients had SLN exclusively in the axilla. Only 10 of 175 (6%) women had internal mammary (IM) SLNs seen on LS. LM identified IM sentinel nodes in 6 of these 10 patients, but none were involved with tumor. Preoperative lymphoscintigraphy and biopsy of internal mammary sentinel nodes do not enhance the accuracy of lymphatic mapping for breast cancer. Omitting lymphoscintigraphy reduces the complexity and cost of lymphatic mapping without compromising the identification of tumor-positive sentinel nodes.