Anaphylaxis to isosulfan blue dye during sentinel lymph node biopsy

We describe a case of intraoperative anaphylaxis resulting from isosulfan blue (IB) dye, an agent being increasingly used for identification of sentinel lymph nodes. A 45-year-old woman undergoing a left mastectomy with sentinel lymph node biopsy under general endotracheal anesthesia developed severe intraoperative hypotension and tachycardia 10 minutes after subcutaneous injection of IB dye for lymphatic mapping. This was associated with a reduction in pulse oximeter reading to 89%. She was successfully resuscitated using 1 mg of epinephrine intravenously (IV). Invasive arterial and central venous pressures were initiated; her lymph node biopsy was concluded, but the rest of her procedure was canceled. Postoperative workup revealed a high tryptase level indicative of an intraoperative anaphylactic reaction most probably related to the IB dye. Isosulfan blue dye can act as an antigen, causing a full-blown intraoperative anaphylactic reaction. Early recognition and aggressive hemodynamic interventions can reduce morbidity and mortality.     

Anaphylactic reaction to patent blue V after sentinel lymph node biopsy

BACKGROUND: We report a documented grade III IgE-mediated hypersensitivity reaction associated with the use of 2.5% patent blue V dye for sentinel lymph node biopsy during breast cancer surgery. METHODS: Immediately after the reaction, when hemodynamic stability was obtained, plasma histamine was measured whereas serum tryptase was not. Six weeks later, with the patient's consent, cutaneous tests to patent blue V dye, methylene blue dye, latex and all drugs used during surgery were performed according to standardized procedures. RESULTS AND CONCLUSION: Clinical symptoms, biological assessment results and cutaneous tests positivity confirmed the onset of an anaphylactic reaction due to patent blue V. Of interest, the positivity of the cutaneous tests observed with patent blue V was not found with methylene blue which might be proposed for further investigations in our patient. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the peri-operative period in case of an immediate hypersensitivity reaction occurring during anesthesia.     

Concordance of peritumoral technetium 99m colloid and subareolar blue dye injection in breast cancer sentinel lymph node biopsy

INTRODUCTION: Sentinel lymph node (SLN) mapping has emerged as a less invasive method for axillary lymph node staging in patients with breast cancer. Blue dye and radioisotopes are commonly used agents to localize SLNs, but the optimal site for the injection of these agents continues to be debated. In this study, we evaluated whether subareolar injection of blue dye led to the identification of the same SLNs as peritumoral injection of technetium colloid. METHODS: From March 2003 to August 2006, 124 patients with invasive breast cancer, diagnosed by core needle biopsy, were included in this study. Demographic and clinical data were abstracted from medical records. Approximately 1 h prior to surgery, all patients had peritumoral injection of 37 Mbq of Tc-99m-sulfur colloid. In the operating room, 3 to 5 mL of 1% lymphazurin was injected into the subareolar area. SLNs were categorized as radio-labeled-only, blue-only, or radio-labeled + blue. Data were analyzed with 95% exact confidence intervals, Spearman rank coefficient and kappa coefficient. RESULTS: The mean number of SLNs identified was 1.9 (range 1-5). With the combination of two methods 122 out of 124 patients (98.4%) had successful identification of SLNs. One hundred fifteen patients (92.7%) had SLNs that were blue and 121 patients (97.6%) had radio-labeled SLNs. One hundred fourteen patients had at least one SLN that was both blue and radio-labeled, yielding a concordance rate of 91.9% (95% CI, 0.88-0.98). Metastatic disease was identified in SLNs of 28 patients. All lymph nodes with evidence of metastasis were both blue and radio-labeled. CONCLUSIONS: Our study showed a high degree of concordance between subareolar blue dye and peritumoral radiocolloid in identification of SLNs. These results further support that the breast parenchyma and subareolar plexus drain to similar SLNs within the axilla. These two techniques can complement each other in localizing SLNs with a high success rate.     

Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.     

Concordance and validation study of sentinel lymph node biopsy for breast cancer using subareolar injection of blue dye and technetium 99m sulfur colloid

BACKGROUND: We have previously demonstrated the utility, accuracy, and advantages of a subareolar (SA) site of injection for blue dye compared with an intraparenchymal site. In later studies we advocated the additional use of preoperative SA-injected technetium 99m-labeled sulfur colloid as a directional aid in finding blue-stained sentinel lymph nodes (SLNs). Paramount to the usefulness of this dual-tracer, same-site technique is the degree to which SA-injected blue dye and SA-injected radiocolloid migrate concordantly and are deposited within the same sentinel nodes. The purpose of this study was to document the correlation and accuracy of SLN biopsy using blue dye and radiocolloid when both nodal markers are injected by the same SA route. STUDY DESIGN: Between September 1999 and February 2002 (29 months), 185 consecutive patients with 187 operable breast cancers underwent 187 attempted SLN biopsies by a dual-tracer, same-site injection technique using the SA approach for both agents. Unfiltered technetium 99m-labeled sulfur colloid (1 mCi [37 MBq]) was SA-injected 30 to 45 minutes preoperatively; and just after anesthetic induction, 3 mL of 1% isosulfan blue dye was injected by the same SA route. SLN biopsies or complete axillary dissections were carried out, and SLNs identified during these procedures were classified as containing both blue dye and radioactivity ("blue-hot" nodes), radioactivity alone ("hot-only" nodes), or blue dye alone ("blue-only" nodes). Cases were categorized and tabulated based on the presence or absence of these three types of SLNs. RESULTS: Of the 187 procedures, a SLN was identified successfully in 184 cases, indicating an SLN identification rate of 98.4% (95% confidence interval, 96.6% to 100.2%). In these 184 cases, a blue-hot node was present in 94.5% (n = 174 of 184). An SLN was positive in 50 cases, or 27.2% of the total group (n = 50 of 184). A blue-hot node was the only positive SLN in 43 of these 50 cases, or 86% of the node-positive cases. There were no false negatives in 20 confirmatory axillary node dissections carried out to document the findings of a negative SLN. A correlation analysis revealed that in 98.9% of cases (174 of 176), blue nodes were also radioactive ("blue-hot" case concordance = 98.9%). In 95.1% of cases (174 of 183), hot nodes had also taken up blue dye ("hot-blue" case concordance = 95.1%). CONCLUSIONS: Using SA injections of both blue dye and radiocolloid, we achieved an SLN identification rate of 98.4% (184 of 187 cases), a false-negative rate of 0% (0 of 20 cases), and an accuracy in predicting the malignant status of the axilla of 100% (70 of 70 cases). The case concordance rate ranged between 98.9% ("blue-hot concordance") and 95.1% ("hot-blue concordance"). The present study is the first to evaluate dual-tracer, same-site SA injections of blue dye and radiocolloid. By demonstrating a high case concordance rate, a high SLN identification rate, and a 0% false-negative rate, this study adds further support to the validity and accuracy of same-site SA injections of both blue dye and radiocolloid during SLN biopsy in breast cancer.     

Allergic reaction to patent blue dye for sentinel lymph node detection during uterus oncological surgery

Patent blue V dye is used to localize the sentinel lymph node during breast and uterine oncological surgery. The case of a grade III anaphylactic reaction related to patent blue dye paracervical injection is described in a 34-year-old woman scheduled for hysterectomy. This complication needs to be rapidly diagnosed to apply adapted supportive treatment.     

Early experience of sentinel lymph node biopsy in breast cancer with blue dye technique

Objective: Sentinel lymph node biopsy (SLNB) is a minimally invasive staging procedure for breast cancer. Results of the first 30 cases of SLNB performed at Kwong Wah Hospital, Hong Kong, were reviewed. Design: This feasibility study applied and assessed a new procedure in Chinese patients. The study was carried out at the Breast Centre, Kwong Wah Hospital, Hong Kong. Sentinel lymph node biopsy was performed with a blue dye technique alone. All patients had full axillary dissection after SLNB. Patients: Female patients with invasive carcinoma of breast and no clinical palpable axillary lymph node were included. Main outcome measures: Pathological results of both the SLN and the remaining axillary content were compared. Results and Conclusion: Sentinel lymph nodes were successfully biopsied in 83% of cases. Sensitivity was 75% and accuracy was 88%. With experience, sentinel lymph node biopsy is feasible in Chinese patients.     

Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during SLNB have recently been reported. No study on the incidence of serious anaphylactic reactions during SLNB for breast cancer has been reported. METHODS: We reviewed 639 consecutive SLNBs for breast cancer performed at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. RESULTS: Overall, 1.1% of patients had severe anaphylactic reactions to isosulfan blue requiring vigorous resuscitation. No deaths or permanent disability occurred. In patients with anaphylaxis, hospital stay was prolonged by a mean of 1.6 days. In 1 patient, the anaphylactic reaction required termination of the operation. CONCLUSIONS: Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis.     

Randomized clinical trial comparing blue dye with combined dye and isotope for sentinel lymph node biopsy in breast cancer

BACKGROUND: Use of blue dye alone as a marker for sentinel lymph node (SLN) biopsy is effective, but combining it with isotope marking can improve the success rate. Use of the isotope adds extra cost and there are potential radiation hazards. The two techniques were compared in a randomized trial. METHODS: Women with early breast cancer (less than 3 cm) and no palpable axillary nodes were recruited. Women older than 70 years with multicentric cancers or previous surgery to the breast or axilla were excluded. Patients were randomized to either blue dye alone or combined mapping for SLN biopsy. All women had a level I and II axillary dissection after the SLN biopsy. RESULTS: A total of 123 patients were recruited, of whom five were excluded from analysis. Blue dye alone was used in 57 women and 61 had combined mapping. Baseline demographic data were similar in the two cohorts. The success rate of SLN biopsy was higher with combined mapping than with blue dye alone (100 versus 86 per cent; P = 0.002). The accuracy and false-negative rate were similar (accuracy 100 per cent for combined mapping versus 98 per cent for blue dye; false-negative rate 0 versus 5 per cent). CONCLUSION: Combined mapping was superior to blue dye alone in identification of the SLN, but accuracy and false-negative rates were similar.     

Comparison of blue dye and isotope with blue dye alone in breast sentinel node biopsy

BACKGROUND: Sentinel lymph node biopsy (SNB) is rapidly gaining acceptance as an alternative to axillary dissection (AD) in patients with early breast cancer. Debate continues regarding the optimum technique for sentinel node (SN) mapping. We have used our series of 364 SNBs to compare two different techniques. METHODS: A retrospective review of patients undergoing SNB by surgeons in our breast service. Overall results were analysed, with particular attention to those having blue dye alone and those having blue dye in combination with radio-labelled colloid. SNs were analysed using haematoxylin-eosin and immunohistochemical staining. RESULTS: SN identification rates were similar: 96% for dye alone and 89% for dye and colloid in combination. Twenty-one per cent of SN mapped with dye alone contained metastases, compared to 30% with dye and colloid in combination. The false-negative rate was correspondingly higher in the dye alone group (21 vs 2.8%). CONCLUSION: SNB using dye and colloid in combination was significantly superior to dye alone in this series. We advocate using both dye and colloid for intraoperative SN mapping.     

Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization

Abstract: Isosulfan blue dye has been used with increasing frequency in localizing sentinel lymph nodes in breast cancer patients. Few alternative types of dye have been investigated. In a prospective study of 30 patients, methylene blue dye was used instead of isosulfan blue dye to localize the sentinel lymph node. The methylene blue dye localization technique was successful in 90% of patients. These results are similar to those for isosulfan blue dye. This study describes methylene blue dye localization as a successful alternative to isosulfan dye in identifying the sentinel node in breast cancer patients. The methylene blue dye technique offers a substantial cost reduction.     

乳腺癌前哨淋巴结亚甲蓝示踪活检术的临床价值

采用 2 %亚甲蓝作示踪剂 ,经根治术同一切口 ,对 85例I～IIIa期乳腺癌患者进行前哨淋巴结活检 (SLNB)。结果示SLNB的成功检出率为 90 .6% (77/85 ) ,准确性为 96.1% (74/77) ,假阴性率为 3 .9% (3 /77)。SLN的转移阳性率为 3 6.4% (2 8/77) ,阴性率为 63 .6% (4 9/77) ,与腋窝淋巴结 (ALN )的转移阳性率 (3 8.8% ,3 3 /85 )和阴性率 (61.2 % ,5 2 /85 )均无统计学差异 (P >0 .0 5 )。SLNB失败的 8例中 ,原发肿瘤位于内上象限 4例 ,中央部 2例 ,外下和外上象限各 1例。假阴性 3例均为T2 N1 期 ,原发肿瘤位于外上象限 ,经洞式探查发现腋尖组 (III组 )淋巴结均有转移。提示应用亚甲蓝示踪的SLNB ,可准确预测乳腺癌ALN的病理学状态。洞式探查III组淋巴结 ,可以弥补SLNB出现假阴性的不足     

Evaluation of the benefit of using blue dye in addition to radioisotope for sentinel lymph node biopsy in patients with breast cancer

The techniques for performing sentinel lymph node biopsy (SLNB) vary from institution to institution. Some advocate blue dye only, others radioisotope only, and many utilize a combination of both. The purpose of this study is to evaluate the additional benefit that blue dye provides when used in combination with a radioisotope. From October 2001 to June 2004, 102 SLNBs were attempted in 99 patients with breast cancer using a combination of blue dye and radioisotope. A lymph node was considered a sentinel lymph node (SLN) when it was stained with blue dye, had a blue lymphatic afferent, or had increased radioactivity. Ninety-eight patients had 101 successful identifications of SLNs, for an identification rate of 99%. Twenty-eight patients had positive SLNs. In three of those patients, although there were SLNs identified by both techniques, the positive SLNs were identified with only blue dye. Of the 102 SLNB procedures, there were two patients whose only SLN was identified by blue dye only. Although blue dye did not improve the identification rate, there was a definite benefit in improving the false-negative rate.     

Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer

Type II pneumocytes synthesize surfactant and differentiate into type I pneumocytes to maintain the epithelium (1). Alveolar type II cell proliferation is required for reepithelization after acute lung injury (ALI) and is thought to minimize the subsequent fibrotic response (1). Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are among the most potent mitogen for type II epithelial cells, but not for fibroblasts in the lung (1). These growth factors attenuate several experimental ALI models by promoting epithelial repair (2,3). Thus, KGF and HGF may be a promising therapeutic approach to ALI. Critically ill patients with ALI often receive IV anesthetics or sedatives to facilitate mechanical ventilation. Furthermore, these patients sometimes undergo bronchoscopy under local anesthesia to obtain bronchoalveolar lavage fluid or to remove respiratory secretions. Several IV and local anesthetics inhibit proliferation of various cells including epithelium (4,5). If these anesthetics impede proliferation of type II pneumocytes, this suppressive effect may be a disadvantage for alveolar reepithelization in the course of recovery from ALI. In this study, we examined the effects of midazolam, propofol, ketamine, thiopental, and lidocaine on proliferation of type II alveolar epithelial cells using in vitro culture system. Because fibroblast proliferation is a key event in late phase of ALI, inhibition of this fibroproliferation is probably beneficial. Thus, we further determined whether these anesthetics could regulate proliferation of lung fibroblasts. In the current study, rolipram was used as a positive control. In our previous preliminary experiment, we found that rolipram, a phosphodiesterase inhibitor type IV, augments spontaneous or KGF-/HGF-promoted type II cell proliferation (6). IMPLICATIONS: Midazolam, ketamine, thiopental, propofol, or lidocaine did not inhibit proliferation of cultured rat type II pneumocytes. Our findings suggest that these anesthetics do not impede alveolar reepithelization after acute lung injury.