Isosulfan Blue Dye Research Articles

A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer

Background Sentinel lymph node biopsy (SLNB) is an established means of staging the axilla in patients with breast cancer. Recently, methylene blue dye has been shown to be an efficacious and cost-effective alternative to isosulfan blue. With the increasing popularity of SLNB, the potential complications of isosulfan blue use must be appreciated. Methods A literature search for English language articles available on MEDLINE from 1985 to November 2002 using the search terms allergy, allergic reaction, anaphylactic reactions, anaphylaxis, blue dye, breast cancer, isosulfan blue, methylene blue, and sentinel lymph node biopsy identified 24 reports. Conclusions The use of isosulfan blue due for SLNB is associated with a significant number of allergic reactions, some of which are life-threatening. Because methylene blue dye has been shown to be equally effective and does not pose a serious risk of serious allergic reactions, it offers an improved technique above isosulfan blue dye for SLNB.

Intraoperative Subareolar Injection of 99mTc-Labeled Sulfur Colloid Results in Consistent Sentinel Lymph Node Identification

Preoperative parenchymal or peritumoral (PT) injection of (99m)Tc-labeled sulfur colloid (TcSC) is the standard method for sentinel lymph node (SLN) identification in patients with breast cancer. Limitations of this method include variable identification rates, slow transit times, and painful injections. We hypothesize that TcSC will travel to the SLN within minutes after injection into the subareolar (SA) lymphatics, thus making an intraoperative injection technique feasible. One hundred twenty-two women with invasive breast cancer were enrolled onto this prospective study. Immediately after the induction of general anesthesia, patients were injected with 1 to 2 mCi of filtered TcSC in the SA location. Then, 5 mL of 1% isosulfan blue dye was injected into the PT location. The SLN or SLNs were identified as radioactive, blue, or both and removed for pathologic evaluation. The mean patient age was 56 years. The mean tumor size was 1.5 cm. In 86.1% of patients, a transcutaneous axillary "hot spot" was identified by handheld gamma probe. The mean time from TcSC injection to axillary incision was 17.6 minutes. At least one SLN was identified in 99.2% of patients. The mean number of SLNs identified per patient was 1.83. The mean count of radioactive SLNs was 2715 cps. In 97.2% of patients, blue SLNs were also radioactive. TcSC injected into the SA lymphatics rapidly drains to the SLN. The radioactive SLN is easily and quickly identified after an intraoperative SA TcSC injection. The simplicity of this method eliminates the inherent problems associated with standard PT injection.

The Role of Sentinel Lymph Node Biopsy with Blue Dye Alone in Breast Cancer Patients with Excisional Biopsy

Purpose : Sentinel lymph node biopsy (SLNB) appears to offer an excellent alternative method to routine axillary lymph node dissection for staging patients with breast cancer. The aim of this study is to evaluate the effect of excisional biopsy on identification and false negative rate of sentinel lymph node biopsy with blue dye alone in breast cancer patients with clinically negative axilla.Material and Methods : From March 1998 to March 2003, 266 consecutive sentinel lymph node biopsies (SLNB) were performed using isosulfan blue dye alone. Patients were divided into two groups. One hundred and four patients (39.1%) had previously undergone an excisional biopsy (Group I); in 162 patients (60.9%), pre-operative diagnosis was obtained by either fine-needle aspiration biopsy (FNAB) or core biopsy (Group II). Following sentinel lymph node biopsy, all patients had axillary lymph node dissection (ALND). Data concerning patients, sentinel lymph nodes and the status of the axilla were collected and compared using Fisher’s exact test. A p value of less than 0.05 was considered statistically significant.Results : The sentinel lymph node was successfully identified by blue dye in 94.3% (251/266) of patients. Mean lymph nodes removed from the axilla was 19 (range 11–36) and the mean number of sentinel nodes was 2 (range 1–5). The identification and false negative rate were unrelated to size, type or location of the tumour, or a previous surgical biopsy. Conclusions : SLNB with blue dye for evaluation of the axilla is a rapid and accurate technique that provides increased efficacy in the detection of lymphatic metastasis when careful pathologic evaluation with serial sections is performed. The risk-benefit analysis of lymphatic mapping with blue dye provides improvement in staging, with reduced morbidity and hospital stay, and the elimination of general anaesthesia. The technique may also be used safely and accurately in breast cancer patients with excisional biopsy.

Sentinel Lymph Node Mapping for Adenocarcinoma of the Colon Does Not Improve Staging Accuracy

This study was designed to: determine the efficacy of sentinel lymph node mapping in patients with intraperitoneal colon cancer; and create an algorithm to predict potential survival benefit by using best-case estimates in favor of sentinel node mapping and lymph node ultraprocessing techniques. Forty-one patients with intraperitoneal colon cancer undergoing colectomy with curative intent were studied prospectively. After mobilization of the colon and mesentery, 1 to 2 ml of isosulfan blue dye was injected subserosally around the tumor. The first several nodes highlighted with blue dye were identified as sentinel nodes. Additional nodes were identified by the pathologist in routine fashion by manual dissection of the mesentery. All nodes were processed in routine fashion by bivalving and hematoxylin and eosin staining. To create an algorithm to predict potential survival benefit of sentinel node mapping and lymph node ultraprocessing techniques, assumptions were made using data from the literature. All bias was directed toward success of the techniques. Three of 41 patients (7 percent) did not undergo injection of dye and were excluded from further analysis. Stage of disease in the remaining 38 patients was: I, n = 10 (26 percent); II, n = 15 (39 percent); III, n = 11 (29 percent); IV, n = 2 (5 percent). At least one sentinel node was identified in 30 of 38 patients (79 percent). The median number of sentinel nodes identified was two (range, 1-3). Median total nodal retrieval was 14 (range, 7-45). All nodes were negative in 26 of 38 patients (68 percent). Sentinel nodes and nonsentinel nodes were positive in 2 of 38 patients (5 percent). Sentinel nodes were the only positive nodes in 1 of 38 patients (3 percent). Sentinel nodes were negative and nonsentinel nodes were positive in 9 of 38 patients (24 percent). Thus, sentinel node mapping would have potentially benefited only 3 percent, and failed to accurately identify nodal metastases in 24 percent of the patients in our study. To create a survival benefit algorithm, we assumed the following: combined fraction of Stage I and II disease (0.5); fraction understaged by bivalving and hematoxylin and eosin staining that would have occult positive nodes by more sophisticated analysis (0.15); fraction of occult positive nodes detected by sentinel node mapping (0.9); and survival benefit from chemotherapy (0.33). Thus, the fraction of patients benefiting from sentinel lymph node mapping and lymph node ultraprocessing techniques would be 0.02 (2 percent). Sentinel node mapping with isosulfan blue dye and routine processing of retrieved nodes does not improve staging accuracy in patients with intraperitoneal colon cancer. Even using best-case assumptions, the percentage of patients who would potentially benefit from sentinel lymph node mapping is small.

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.

Total laparoscopic radical hysterectomy with intraoperative sentinel node identification in patients with early invasive cervical cancer

Objectives To describe the feasibility and results of total laparoscopic radical hysterectomy with intraoperative sentinel lymph node identification in patients with early cervical cancer. Methods Between March 2001 and October 2003, 12 patients with FIGO stage IA 2 ( n = 1) or IB 1 ( n = 11) cancer of the cervix underwent surgical treatment through the laparoscopic route. All patients underwent a laparoscopic sentinel node identification with preoperative lymphoscintigraphy (technetium-99 m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with isosulfan blue dye and a laparoscopic gamma probe followed by systematic bilateral pelvic lymphadenectomy and laparoscopic type II ( n = 5) or type III ( n = 7) hysterectomy. Results A mean of 2.5 sentinel nodes per patient (range 1−4) was detected, with a mean of 2.33 nodes per patient by gamma probe and a mean of 2 per patient after blue injection (combined detection rate 100%). The most frequent localization of the nodes was the interiliac region. Histopathologic examination of sentinel nodes including cytokeratin immunohistochemical analysis did not show metastasis. Microscopic nodal metastases were not found. The mean number of resected pelvic nodes was 18.6 per patient (range 10–28). The operation was performed entirely by laparoscopy in all patients and no case of laparotomy conversion was recorded. The mean duration of operation was 271 min (range 235–300), with a mean blood loss of 445 mL (range 240–800), and a mean length of stay of 5.25 days (range 3−10). No major intraoperative complications occurred. After a median follow-up of 20 months (range 5–34), all patients are free of disease. Conclusions This study shows the feasibility of the combination of laparoscopic intraoperative sentinel node mapping and laparoscopic radical surgery in the context of minimally invasive surgery for the management of patients with early cervical cancer.

Ex Vivo Lymphatic Mapping: A Technique to Improve Pathologic Staging in Colorectal Cancer

Sentinel lymph node (SLN) biopsy is widely used for solid tumors and has been proposed for use in staging colorectal cancer (CRC). Few studies have examined the ex vivo lymphatic mapping (EVLM) technique for staging CRC. We hypothesized that EVLM is technically feasible, sensitive, accurate, and improves the staging of CRC. After standard resection for colorectal cancer, 1 mL of isosulfan blue dye was injected circumferentially around the tumor. Blue-stained nodes were dissected separately and examined by hematoxylin and eosin (H&E) and immunohistochemical (IHC) stains. Routine pathologic evaluation was performed on all other harvested lymph nodes. Forty patients underwent 43 cancer resections with EVLM from July 2000 to December 2003. SLN were identified in 39 of 43 (91%) specimens. The mean number of SLN obtained was 1.9 (range, 0-5). Pathologic evaluation demonstrated nodal metastasis in 16 of 39 (39%) specimens. The SLN was tumor-positive in 9 of these 16 (56%) patients. The overall accuracy of EVLM was 82%. Two patients (9%) with H&E node negative disease were upstaged when found to have micrometastases by IHC staining. In conclusion, EVLM is technically possible in 90 per cent of patients with CRC. Although overall accuracy was high, the SLN status correlated poorly with the true nodal status of the CRC. However, EVLM improves pathologic staging in 9 per cent of patients and therefore may be of value in CRC.

Comparative Analysis of Nodal Upstaging Between Colon and Rectal Cancers by Sentinel Lymph Node Mapping: A Prospective Trial

Sentinel lymph node mapping accurately predicts nodal status in > 90 percent of melanoma and breast and colorectal cancers. However, because of anatomic differences, sentinel lymph node mapping of rectal cancers has been considered inaccurate and difficult relative to colon. A prospective study was undertaken to identify differences in sentinel lymph node mapping between patients with colon cancer and those with rectal cancer. At operation 1 to 3 ml of 1 percent isosulfan blue dye was injected subserosally around colon cancers. The first to fourth blue-staining nodes seen within ten minutes of injection were marked as sentinel lymph nodes. For cancer of the mid-rectum to low rectum, the dye was injected submucosally via rigid scope and spinal needle. The mesorectum was dissected ex vivo to identify blue nodes nearest the tumor as sentinel lymph nodes. Multilevel microsections of sentinel lymph nodes were stained with hematoxylin and eosin and immunostained for cytokeratin, and standard examination of the entire specimen was performed. There were 407 consecutive patients (336 with colon and 71 rectum). The sentinel lymph nodes were identified in 99.1 percent of colon and 91.5 percent of rectal patients (P < 0.0001). Skip metastases were found in 3.6 percent of colon vs. 2.8 percent of rectal patients (P = 0.16). Occult micrometastases were found in 13.4 percent of colon vs. 7.0 percent of rectal patients (P = 0.24). Except for success rates, no other parameters were statistically different between colon and rectum. Lower success in sentinel lymph node identification in rectal cancer may have been related to neoadjuvant chemoradiation received in all six of the patients with sentinel lymph node mapping failures. Despite higher success rates in sentinel lymph node identification for colon patients, sentinel lymph node mapping was highly successful (91.5 percent) in rectal patients. Nodal upstaging, skip metastases, and occult metastases were similar.

Sentinel Lymph Node Mapping of Breast Cancer: A Case-Control Study of Methylene Blue Tracer Compared to Isosulfan Blue

Isosulfan blue has been traditionally used as a tracer to map the lymphatic system during identification of the sentinel lymph node. However, allergic reactions may be life threatening. We compared the efficacy of methylene blue dye as a tracer for sentinel lymph node biopsy to isosulfan blue dye. In an analysis of 164 cases, there was no clinical or statistically significant difference in the success rate of sentinel node biopsy (P = 0.22), the number of blue sentinel nodes harvested (P = 0.46), the concordance with radioactive sentinel nodes (P = 0.92), or the incidence of metastases (P = 0.87) when methylene blue tracer was compared to isosulfan blue. No adverse reaction to either blue dye was observed. In conclusion, intraparenchymal injection of methylene blue dye is a reliable tracer for the lymphatic system and nodal identification during sentinel node mapping for breast cancer. It is safe, inexpensive, and readily available.

Experience with sentinel lymph node biopsy for eyelid and conjunctival malignancies

7549 Background: To describe our experience with sentinel lymph node (SLN) biopsy in patients with eyelid and conjunctival melanoma, Merkel cell carcinoma of eyelid, and sebaceous cell carcinoma of the eyelid. Methods: 20 patients with eyelid or conjunctival malignancies mentioned above were treated at The University of Texas M. D. Anderson Cancer Center between May 2002 and July 2003, had clinically and radiographically negative regional lymph nodes, and underwent preoperative lymphoscintigraphy using an injection of technetium Tc-99m (0.3 mCi) in 0.2 mL volume. Intraoperative mapping was performed with the same volume of technetium Tc-99m along with an injection of isosulfan blue dye. Results: 6 patients had conjunctival melanoma, 6 had eyelid sebaceous cell carcinoma, 6 had eyelid melanoma, and 2 had eyelid Merkel cell carcinoma. SLN(s) were identified in all patients. Intraoperatively, no SLN(s) were blue. 1 patient with conjunctival melanoma and 1 patient with Merkel cell carcinoma had a histological...

Experience with sentinel lymph node biopsy for eyelid and conjunctival malignancies at a cancer center.

To describe one center's experience with sentinel lymph node (SLN) biopsy in patients with eyelid and conjunctival malignancies performed with a smaller volume of technetium than was initially used and a small incision directly overlying the sentinel node(s). A noncomparative interventional case series of 13 patients with clinically negative regional lymph nodes who underwent SLN biopsy for eyelid or conjunctival malignancies at The University of Texas M. D. Anderson Cancer Center between May 2002 and July 2003. Preoperative lymphoscintigraphy was performed with an injection of 0.3 mCi of technetium Tc-99m sulfur colloid in a volume of 0.2 mL. Images were taken as soon as the first SLN was detected through the gamma camera. Intraoperative mapping was performed with the same volume and concentration of technetium Tc-99m sulfur colloid along with an injection of isosulfan blue dye. Five patients had conjunctival melanoma, 6 had sebaceous cell carcinoma of the eyelid, and 2 had eyelid melanoma. SLN(s) were identified in all patients. In 12 patients, more than 1 SLN was identified. During surgery, no SLNs were blue. One patient with conjunctival melanoma had an SLN that was positive on histologic examination. There were no ocular or extraocular complications from the procedure except for mild temporary weakness of the marginal mandibular branch of the facial nerve in 2 patients that resolved completely within 4 to 6 weeks and without any further intervention. None of the patients had permanent blue tattooing of the conjunctival surface or eyelid skin. Our experience suggests that lymphoscintigraphy and SLN biopsy with a small volume of technetium Tc-99m sulfur colloid and small incisions, even without the use of the blue dye, can identify SLNs in patients with conjunctival and eyelid malignancies, and can be performed safely.

Patterns of drainage and recurrence following sentinel lymph node biopsy for cutaneous melanoma of the head and neck.

To analyze lymphatic drainage patterns and recurrence patterns in patients undergoing sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanoma. Retrospective review of a consecutive series with a mean follow-up of 35 months. Tertiary cancer care center. Fifty-one patients with clinically node-negative cutaneous melanoma of the head and neck region staged by means of SLNB. Sentinel lymph nodes (SLNs) were identified using preoperative lymphatic mapping along with intraoperative gamma probe evaluation and isosulfan blue dye injection. Patients with a positive SLNB finding by hematoxylin-eosin or immunohistochemical evaluation underwent completion lymphadenectomy of the affected lymphatic basin and were considered for further adjuvant treatment. Patients with a negative SLNB finding were observed clinically. Location characteristics of SLNs, incidence of positive SLNs, same-basin recurrence, and disease-free survival. The mean number of SLNs per patients was 2.75. The extent of SLNB included removal of 1 node (n = 11), multiple nodes from 1 basin (n = 18), 1 node in multiple basins (n = 7), and multiple nodes in multiple basins (n = 15). Drainage to unexpected basins was found in 13 of 51 patients. Parotid region drainage was identified in 18 patients. There were no same-basin recurrences in patients with a negative SLNB finding. Thirty-six-month disease-free survival was 88.9% for patients with a negative SLN and 72.9% for patients with a positive SLN (P=.17). The number and location of SLNs is variable and difficult to predict for head and neck cutaneous melanoma. Preoperative lymphoscintigraphy is an important planning instrument to guide complete removal of all SLNs. Based on 3-year follow-up, this procedure can be expected to provide low same-basin recurrence rates for patients with a negative SLN.

Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma.

The feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) for patients with breast carcinoma have been investigated primarily for the situation in which the radiocolloid imaging agent is injected peritumorally. No such study has involved periareolar injection of radiocolloid, although the usefulness of this injection technique has been demonstrated in patients with early-stage breast carcinoma who have not been treated with NAC. The objective of the current study was to determine the feasibility and accuracy of SLN biopsy using periareolar injection of radiocolloid for patients with breast carcinoma who were treated with NAC. Forty-seven patients with AJCC Stage II or III breast carcinoma who were treated with NAC were enrolled in the study. All patients underwent SLN biopsy, which involved a combination of periareolar injection of radiocolloid (technetium 99m tin colloid) and peritumoral injection of isosulfan blue dye, followed by backup axillary lymph node dissection. SLN metastases were examined by hematoxylin and eosin staining and immunohistochemical analysis using an anticytokeratin antibody. An SLN was identified successfully in 44 patients (94%). Twenty-nine patients (66%) had positive SLNs. Fifteen patients had negative SLNs, and 4 patients had positive non-SLNs. Thus, the false-negative rate was 12.1% (4 of 33 patients). The false-negative rate tended to be higher, although not statistically significantly so, among patients who had clinically positive axillary lymph nodes before and/or after NAC (15.8%; 3 of 19 patients) compared with patients who had clinically negative axillary lymph nodes both before and after NAC (7.1%; 1 of 14 patients). SLN biopsy using periareolar injection of radiocolloid is feasible after NAC. In patients with clinically negative axillary lymph nodes both before and after NAC, SLN biopsy was capable of predicting axillary lymph node status with an accuracy comparable to the accuracy associated with SLN biopsy for patients with early-stage carcinoma who have not been treated with NAC.

Sentinel lymph node mapping and selective lymphadenectomy: the standard of care for melanoma.

Selective sentinel lymphadenectomy (SSL) should be considered a standard of care approach for staging patients with primary invasive melanoma 1 mm or greater. It is essential that multidisciplinary teams should master the techniques of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and pathologic evaluation of the sentinel lymph nodes (SLNs). An SLN may be blue, hot, or any lymph node (LN) greater than 10% of the in-vivo count of the hottest LN. An enlarged or indurated LN should be removed because it may contain metastatic cancer cells that block blue dye or radiotracer entry. Frozen sections are not recommended. Surgeons who use isosulfan blue dye should be cognizant of treatment for a potentially fatal reaction. Prophylactic LN dissection should not be performed if a SSL can be performed as a staging procedure. A complete LN dissection is performed if the SLN is positive. It is important to follow the clinical outcome of patients undergoing SSL, thus its role can be further defined.

Technical Advances in Sentinel Lymph Node Biopsy for Breast Cancer

Technical advances in the past several years have simplified and improved sentinel lymph node (SLN) biopsy for breast cancer. The use of alternative injection sites (skin or subareolar) yields high SLN identification rates and may shorten the learning curve associated with standard peri-tumoral injection. The dual-agent (radiocolloid plus blue dye) technique is now recommended to decrease false-negative rates, especially when surgeons are just learning how to perform SLN biopsy. Methylene blue may be an acceptable substitute for isosulfan blue dye and is associated with fewer hypersensitivity reactions. Hand-held gamma probes are now smaller and more maneuverable, with better shielding for directional detection of gamma rays. Routine preoperative lymphoscintigraphy can be avoided, thus facilitating operating room scheduling. Surgeons can use minimally invasive techniques to identify and remove internal mammary SLNs.

A prospective evaluation of radiocolloid and immunohistochemical staining in colon carcinoma lymphatic mapping.

Although the utility of lymphatic mapping (LM) and sentinel lymph node (SLN) biopsy in patients with melanoma and breast carcinoma has been well documented, this same is not true for patients with colon carcinoma. The authors previously reported a high false-negative rate for SLN biopsy in patients with colon carcinoma using isosulfan blue dye alone. The objective of the current study was to determine whether radiocolloid would increase the sensitivity of LM/SLN biopsy in patients with colon carcinoma. The authors performed LM on 57 patients with colon carcinoma using both isosulfan blue dye and radiocolloid. The SLN(s) were identified by either their blue color or by increased radioactivity. The SLNs then underwent both routine histologic sectioning and immunohistochemical (IHC) staining for cytokeratins. An SLN was identified in 56 patients (98%). Radiocolloid was able to identify only 1 additional positive SLN (9%). Overall, it was found that the disease had metastasized to the lymph nodes in 22 patients, even though there was no evidence of disease in the SLN(s) in 11 of those 22 patients on routine histologic sectioning (false-negative rate, 50%; sensitivity, 50%). In five patients, IHC of the SLN was the only indicator of metastatic disease. The inclusion of IHC-positive SLNs in these calculations would decrease the false-negative rate to 17% and would increase the sensitivity of SLN biopsy to 83%. In the current study, the addition of radiocolloid did not increase the sensitivity of detection of positive SLN(s) compared with the use of isosulfan blue dye alone. IHC of the SLN potentially may increase the sensitivity of LM and reduce the false-negative rate. However, the long-term prognostic significance of IHC in patients with colon carcinoma remains controversial.

Pathologic Evaluation of Inguinal Sentinel Lymph Nodes in Patients With Vulvar Cancer: A Comparison of Immunohistochemical Staining versus Ultrastaging With Hematoxylin and Eosin Staining

The authors identified 29 patients with squamous cell carcinoma of the vulva who had undergone inguinal sentinel lymph node dissection based on ultrastaging with hematoxylin and eosin staining. Isosulfan blue dye was used to identify sentinel nodes. After removal, each node was sectioned at 2-mm intervals for submission to histology. Two parallel slides were cut from each of 5 100-μm intervals in the section. One slide from each pair was stained with hematoxylin and eosin and subjected to ultrastaging. The parallel of each slide diagnosed as negative for micrometastases underwent immunohistochemical staining using a pancytokeratin cocktail AE1/AE3 (BioGenex Corp., San Ramon, CA), a streptavidin-biotin detection system, and AEC chromogen. They were then lightly counterstained with hematoxylin for review. In all, 107 sentinel lymph nodes were removed. Of these, 18 were diagnosed as positive and 89 were negative. The results of reevaluation of negative nodes with immunohistochemical staining of the parallel slide were negative in all 89 parallel slides. No differences in the detection of disease were seen between staining with hematoxylin and eosin and immunohistochemical staining.

Clinical practice guidelines for the use of axillary sentinel lymph node biopsy in carcinoma of the breast: current update.

Axillary sentinel lymph node biopsy (SLNB) has been adopted as a suitable alternative to traditional level I and II axillary dissection in the management of clinically node-negative (N0) breast cancers. There are two current techniques used to identify the sentinel node(s): radiopharmaceutical, technetium sulfur colloid, and isosulfan blue dye (used in the United States) and technetium-labeled albumin and patent blue dye (used in Europe). (The labeled albumin is not U.S. Food and Drug Administration [FDA] approved in the United States.) SLNB to replace axillary dissection should only be performed by surgeons and patient management teams with appropriate training and experience. Although both radiocolloid and blue dye are used together by most surgeons, and training should be in both techniques, some experienced surgeons use one or the other almost exclusively. In addition, surgical pathologists must recognize the need to examine these small specimens with great care, using a generally adopted protocol. Imprint cytology or frozen sections may be used, followed by additional sections for light microscopy. Immunochemical staining with cytokeratin or other techniques to identify "submicroscopic" metastasis is often used, but the results should not be used to influence clinical decisions with respect to adjuvant therapy. "Failed" SLNB implies the surgeon's failure to identify the sentinel nodes, in which case a complete dissection is performed. A "false-negative" SLNB implies the finding of metastasis in the excised sentinel nodes by light microscopy after a negative frozen section examination. Whether a false-negative SLNB mandates completion axillary dissection is controversial, with clinical trials currently under way to answer this question. Although SLNB was initiated to accompany breast-conserving treatment, it is equally useful in patients undergoing mastectomy. It is more difficult to perform with mastectomy. When using blue dye only, SLNB may require a separate incision because of time constraints between injection and identification of the blue-stained nodes; radiocolloid usually does not. Completion axillary dissection after false-negative SLNB is more difficult after mastectomy. SLNB is a useful procedure that may save 70% of women with clinically negative (N0) axillae and all of those with pathologically negative axillae from the morbidity of complete axillary dissection. Ideally the sentinel nodes should be able to identified in more than 95% of patients, with a false-negative rate of less than 5%. Until these rates can be achieved consistently, however, surgeons should not abandon traditional axillary dissection.

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.

HER2/neu Expression and Hormonal Therapy in Early Breast Cancer: Can Muddy Waters Become Clear?

prophylaxis regimen included a corticosteroid, we monitored our outcomes for wound complications. Although the complication rate was two-fold greater in patients receiving prophylaxis and dye compared with those receiving neither, this was not statistically significant. Several mechanisms of action behind adverse reactions to isosulfan blue dye have been postulated, but none have been confirmed. We are currently investigating the molecular basis of these adverse reactions.