V. Suzanne Klimberg

Subareolar Versus Peritumoral Injection for Location of the Sentinel Lymph Node

BACKGROUND Sentinel lymph node (SLN) biopsy is fast becoming the standard for testing lymph node involvement in many institutions. However, questions remain as to the best method of injection. The authors hypothesized that a subareolar injection of material would drain to the same lymph node as a peritumoral injection, regardless of the location of the tumor. METHODS To test this theory, 68 patients with 69 operable invasive breast carcinomas and clinically node-negative disease were enrolled in this single-institution Institutional Review Board-approved trial. Patients were injected with 1.0 mCi of technetium-99 sulfur colloid (unfiltered) in the subareolar area of the tumor-bearing breast. Each patient received an injection of 2 to 5 cc of isosulfan blue around the tumor. Radioactive SLNs were identified using a hand-held gamma detector probe. RESULTS The average age of patients entered into this trial was 55.2 +/- 13.4 years. The average size of the tumors was 1.48 +/- 1.0 cm. Thirty-two percent of the patients had undergone previous excisional breast biopsies. Of the 69 lesions, 62 (89.9%) had SLNs located with the blue dye and 65 (94.2%) with the technetium. In four patients, the SLN was not located with either method. All blue SLNs were also radioactive. All located SLNs were in the axilla. Of the 62 patients in which the SLNs were located with both methods, an average of 1.5 +/- 0.7 SLNs were found per patient, of which 23.2% had metastatic disease. All four patients in which no SLN was located with either method had undergone prior excisional biopsies. CONCLUSIONS The results of this study suggest that subareolar injection of technetium is as accurate as peritumoral injection of blue dye. Central injection is easy and avoids the necessity for image-guided injection of nonpalpable breast lesions. Finally, subareolar injection of technetium avoids the problem of overlap of the radioactive zone of diffusion of the injection site with the radioactive sentinel lymph node, particularly in medial and upper outer quadrant lesions.

Use of touch preps for intraoperative diagnosis of sentinel lymph node metastases in breast cancer

AbstractBackground: Intraoperative touch prep (TP) is highly accurate for determining positive breast cancer margins and thereby reducing the need for second surgeries. It also may be useful in determining the status of the sentinel lymph node (SLN) during the initial surgical resection. The objective of this study was to test the ability of intraoperative TP to predict metastatic disease and, thus, the necessity for axillary lymph node dissection (ALND) at the time of SLN biopsy. Methods: Fifty-five patients with invasive breast cancer were entered in the SLN biopsy protocol. The SLN was identified by gamma probe, dissected, and sent to pathology for TP and permanent sections. Level I and II ALND was then performed. Any radiolabeled LN in the lymphadenectomy specimen also was sent for TP and permanent sections. Results: A total of 124 radiolabeled lymph nodes (LNs) were submitted for TP; of these, 93 (75%) were SLNs. Pathologic diagnosis by TP was correct compared with permanent sections for 99.2% of the nodes. There were no false positives. There was one (0.8%) false negative. The positive predictive value was 100% and the negative predictive value was 99%. Sensitivity was 95.7% and specificity was 100%. Conclusions: TP is a simple, quick, and accurate method for detecting metastatic disease in the SLN and, when used intraoperatively, enables the surgeon to determine whether or not an ALND is necessary at the time of the initial surgery.

Axillary Reverse Mapping (ARM): A New Concept to Identify and Enhance Lymphatic Preservation

BackgroundVariations in arm lymphatic drainage put the arm lymphatics at risk for disruption during axillary lymph node surgery. Mapping the drainage of the arm with blue dye (axillary reverse mapping, ARM) decreases the likelihood of disruption of lymphatics and subsequent lymphedema.MethodsThis institutional review board (IRB)-approved study from May to October 2006 involved patients undergoing SLNB and/or ALND. Technetium sulfur colloid (4 mL) was injected in the subareolar plexus and 2–5 mL of blue dye intradermally was injected in the ipsilateral upper extremity (ARM). Data were collected on variations in lymphatic drainage that impacted SLNB or ALND, successful identification and protection of the arm lymphatics, any crossover between a hot breast node and a blue arm node, and occurrence of lymphedema.ResultsOf the 40 patients undergoing surgery for breast cancer, 18 required an ALND, with a median age of 49.7 years old. Fourteen patients had a SLNB + ALND, and four patients had ALND alone. In 100% of patients, all breast SLNs were hot but not blue, and the false negative rate was 0. In 11 of 18 ALNDs (61%) blue lymphatics or blue nodes were identified in the axilla. In the initial seven cases with positive lymph nodes in the axilla, the blue node draining from the arm was biopsied and all were negative.ConclusionsARM identified significant lymphatic variations draining the upper extremities and facilitated preservation in all but one case. ARM added to present-day ALND and SLNB further defines the axilla and may be useful to prevent lymphedema.

Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer

AbstractBackground: The best cosmetic results with conservative breast surgery are obtained at the time of initial excisional biopsy. The usefulness of the touch prep (TP) technique was evaluated for accuracy in diagnosis as well as in evaluation of margins at the time of original breast biopsy. Methods: Four hundred twenty-eight consecutive patients with breast masses seen from January 1993 to December 1994 were evaluated prospectively using TP. Results: Three hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to permanent section in 99.3%. The three carcinomas missed on TP were focal and in situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 99.3%. For margin evaluation, the sensitivity and specificity were both estimated to be 100%. Conclusions: TP has the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of diagnostic material), and accurate method for diagnosis and estimation of tumor margins at the time of the original surgery.

Assessing margin status

As little time ago as 1991 the NIH Consensus conference could not agree on the need for negative margins. Today, negative margin status has become a prerequisite for BCT recognizing that positive margins impact negatively on local recurrence rates. The science of margin evaluation is fast becoming recognized to play a key role in providing patients with the opportunity for breast conservation therapy as well as the best possible cosmetic result. Preoperative factors that predict a greater likelihood of failure to obtain margins such as larger tumor size and positive lymph nodes are fixed and can only be dealt with by taking larger biopsies. RODEO-MRI can preoperatively predict probability of success or failure and can actual better define tumor dimensions and extent and help plan excisions. Use of intraoperative US may be a future tool used to facilitate the excision of non-palpable and possibly palpable tumors. Intraoperative pathological assessment should not be performed by frozen section but consideration given to cytological assessment so as to allow feedback to the surgeon intraoperatively as to which margin needs more attention. Finally, using all the above methods of obtaining negative margins, the surgeon may have the ability to impact the outcome of breast cancer surgery and recurrence.

Glutamine Enhances Gut Glutathione Production

BACKGROUND The gastrointestinal tract is recognized as having important metabolic functions. This study examined gut glutathione (GSH) extraction and the effect of supplemental oral glutamine (GLN) on gut GSH fractional release. METHODS Healthy female Fisher-344 rats weighing approximately 150 to 200 g were pair-fed chow and supplemented by gavage with 1 g/kg/d GLN or an isonitrogenous amount of Freamine (McGaw, St. Louis, MO). Rats were sacrificed at 6 weeks. Arterial and portal blood was assayed for GLN and GSH content. The gut GLN and GSH extractions were calculated. RESULTS The gut GLN fractional uptake was increased by approximately 50%, and there was a near threefold increase in gut GSH fractional release in the GLN-supplemented group. CONCLUSIONS The discovery of guts role as a major producer of GSH may give insight into why feeding via the gut rather than by the venous route is so important. Supplemental oral GLN further enhances GLN extraction as well as GSH fractional release in the gut.

Oncologic Safety of Nipple Skin-Sparing or Total Skin-Sparing Mastectomies With Immediate Reconstruction

BACKGROUND Success with skin-sparing mastectomy (SSM) has led to the reconsideration of the necessity to remove the skin overlying the nipple-areola complex. The aim of our study was to compare complications and local recurrence in patients undergoing SSM and total skin-sparing mastectomy (TSSM) with immediate reconstruction. METHODS This IRB-approved retrospective study involved patients who underwent mastectomy with reconstruction (1998 to 2010). Patient demographics, tumor characteristics, type of surgery, cosmesis, postoperative complications, and recurrence were analyzed. RESULTS The 293 patients in our study group had a total of 508 procedures: 281 TSSMs and 227 SSMs, distributed among 215 patients with bilateral procedures and 78 with unilateral operations. Mean age was 51.2 ± 10.9 years for TSSM and 53.1 ± 11.5 years for SSM. The average tumor size was 1.9 ± 1.6 cm for TSSM versus 2.1 ± 1.7 cm for the SSM group. The overall complication rate (TSSM 7.1% [20 of 281] and SSM 6.2% [14 of 227], p = 0.67) and local-regional recurrence rate (TSSM 6% [7 of 152] and SSM 5.0% [7 of 141], p = 0.89) were comparable. The TSSM rating was significantly higher (score 9.2 ± 1.1) than the SSM group (score 8.3 ± 1.9, p = 0.04). CONCLUSION TSSM appears to be oncologically safe with superior cosmesis, affords one-step immediate reconstruction, and can be offered to patients with stages I and II breast cancer and those who have been down-staged with neoadjuvant chemotherapy.

Sentinel lymph node biopsy for staging breast cancer

BACKGROUND Determination of axillary nodal status is essential for the staging of breast cancer since nodal status is one of the most important predictors of survival. The objective of this study was to test the hypothesis that the histology of the first draining lymph node (LN) accurately predicts the histology of the rest of the axillary LNs. METHODS Fifty-five patients with operable invasive breast carcinoma and clinically negative axillary lymph nodes were studied. Patients were injected with Technetium-99 (99Tc) sulfur colloid around the primary tumor. A hand-held gamma detector probe was used to identify the sentinel LN (SLN). After the SLN was identified and removed, a level I and II lymphadenectomy was performed. RESULTS The SLN was identified in 53 (96.3%) of the 55 patients entered into the trial. The sensitivity was 88.2% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94.6%. The accuracy of the study was 96.2%. CONCLUSIONS The SLN biopsy for breast cancer staging is highly accurate in our hands and has the potential to decrease the morbidity and cost of managing patients with breast cancer without compromise of staging.

Axillary Reverse Mapping: Mapping and Preserving Arm Lymphatics May Be Important in Preventing Lymphedema During Sentinel Lymph Node Biopsy

BACKGROUND Several recent reports have shown a lymphedema rate of about 7% with sentinel lymph node biopsy (SLNB) only. We hypothesized that this higher than expected rate of lymphedema may be secondary to disruption of arm lymphatics during an SLNB procedure. STUDY DESIGN This IRB-approved study, from May 2006 to June 2007, involved patients undergoing SLNB with or without axillary lymph node dissection. After sentinel lymph node (SLN) localization with subareolar technetium was assured, 2 to 5 mL of dermal blue dye was injected in the upper inner arm for localization of lymphatics draining the arm (axillary reverse mapping, ARM). The SLNB was then performed through an incision in the axilla. Data were collected on identification rates of hot versus blue nodes, variations in ARM lymphatic drainage that might impact SLNB, crossover between the hot and the blue lymphatics, and final pathologic nodal diagnosis. RESULTS Median age was 57.6+/-12.5 years. Lymphatics draining the arm were near or in the SLN field in 42.7% (56 of 131) of the patients, placing the patient at risk for disruption if not identified and preserved during an SLNB or axillary lymph node dissection. ARM demonstrated that arm lymphatics do not cross over with the SLN drainage of the breast 96.1% of the time and that none of the ARM lymph nodes removed were positive, even when the SLN was (5 of 12). Seven (5.5%) blue ARM lymphatics were juxtaposed to the hot SLNBs. CONCLUSIONS Disruption of the blue ARM node because of proximity to the hot SLN may explain the surprisingly high rate of lymphedema seen after SLNB. Identifying and preserving the ARM blue nodes may translate into a lower incidence of lymphedema with SLNB and axillary lymph node dissection.

Intraoperative ultrasound-guided breast biopsy

BACKGROUND Biopsy of nonpalpable lesions has increased during the last decade. Commonly these lesions are excised using preoperative wire localization. We describe a technique of intraoperative ultrasound-guided breast biopsy that allows easier excision and aids in obtaining surgical margins in breast cancer. METHODS Intraoperative ultrasound was performed on 81 lesions. Ultrasound was used in an attempt to approximate a 1 cm margin on malignant lesions. RESULTS All attempts to localize lesions with ultrasound in surgery were successful (81 of 81). Ultrasound-guided surgery was accurate in predicting margins in 24 of 25 malignant lesions. No complications resulted. CONCLUSION Ultrasound proved to be an effective technique for localizing and excising breast lesions. Benefits may include improving patient comfort, avoiding complications of needle localization breast biopsy, and simplifying the scheduling of surgical procedures. Additionally, this procedure may be used to obtain adequate surgical margins and thus reduce the recurrence rate of breast cancer.