C. Matthew Brown

Sentinel Lymph Node Biopsy for Breast Cancer: A Suitable Alternative to Routine Axillary Dissection in Multi-Institutional Practice When Optimal Technique Is Used

PURPOSE Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

ObjectiveTo determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. Summary Background DataThe optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. MethodsThe University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1–2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. ResultsA total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. ConclusionsDermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Defining the Optimal Surgeon Experience for Breast Cancer Sentinel Lymph Node Biopsy: A Model for Implementation of New Surgical Techniques

ObjectiveTo determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. Summary Background DataBefore abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. MethodsAnalysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. ResultsA total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. ConclusionsSurgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.

Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes

OBJECTIVE To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. METHODS After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. RESULTS Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. CONCLUSIONS Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.

Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.

BACKGROUND Intraoperative frozen section pathologic analysis of sentinel lymph node (SLN) may guide immediate (single-stage) completion axillary dissection for patients with nodal metastases. METHODS The results of 203 consecutive patients undergoing SLN biopsy who had intraoperative pathology consultation between January 1998 and September 2000 were reviewed. SLN were analyzed by standard frozen section procedures. Final pathologic analysis included hematoxylin and eosin (H&E) staining of serial sections at 2-mm intervals. RESULTS Frozen section analysis correctly identified a positive or negative result in 185 of 203 cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor by frozen section, but positive on permanent section analysis (sensitivity 68%). The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to have true positive and false negative results, respectively (P <0.003). A single false positive SLN is reported. CONCLUSIONS Two thirds of the patients were spared the need for reoperative axillary lymphadenectomy.

The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy

BackgroundIt has been suggested that sentinel lymph node (SLN) biopsy for breast cancer may be less accurate after excisional biopsy of the primary tumor compared with core needle biopsy. Furthermore, some have suggested an improved ability to identify the SLN when total mastectomy is performed compared with lumpectomy. This analysis was performed to determine the impact of the type of breast biopsy (needle vs. excisional) or definitive surgical procedure (lumpectomy vs. mastectomy) on the accuracy of SLN biopsy.MethodsThe University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study. Patients with clinical stage T1–2, N0 breast cancer were eligible. All patients underwent SLN biopsy and completion level I/II axillary dissection. Statistical comparison was performed by χ2 analysis.ResultsA total of 2206 patients were enrolled in the study. There were no statistically significant differences in SLN identification rate or false-negative rate between patients undergoing excisional versus needle biopsy. The SLN identification and false-negative rates also were not statistically different between patients who had total mastectomy compared with those who had a lumpectomy.ConclusionsExcisional biopsy does not significantly affect the accuracy of SLN biopsy, nor does the type of definitive surgical procedure.

Muramyl dipeptide protects decomplemented mice from surgically-induced infection

Muramyl dipeptide (MDP) is a natural product of bacterial cell-wall breakdown, which can now be produced synthetically; it is the smallest component of the mycobacterial cell wall capable of reproducing the adjuvant activities of Freunds complete adjuvant. We tested the well-documented, protective effect of MDP to increase survival in a murine model simulating surgically-induced bacteremia. The protocol involved the bacterial innoculation of control and decomplemented mice in the presence and the absence of pretreatment with MDP. Bacteremia in both the control and decomplemented groups pretreated with MDP was decreased statistically at 24 h (P less than 0.01) as compared to controls. Likewise, survival was increased significantly at 24 h (P less than 0.05), 48 h (P less than 0.001), and 72 h (P less than 0.001) using the same group comparisons. We conclude, therefore, that MDP maintains its protective effect in the absence of complement, supporting the view that the mechanism of action of MDP is complement independent.