Sandra F. Grant

Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma-detecting probe

Sentinel node staging for breast cancer is increasingly used in place of axillary lymph node dissection but is not yet universally accepted. The problems of non-standardized methodologies and lack of consensus on the optimum techniques to identify sentinel nodes are being addressed. Complementary use of radionuclide imaging before surgery, intraoperative probe detection, and blue dye have yielded the best reported sensitivities for finding a sentinel node (94%). The importance of imaging is summarized as identifying sentinel node(s), distinguishing sentinel from secondary nodes, guiding surgical incision planning, and facilitating lower doses. The learning curve phenomenon, which applies to the surgeon and the nuclear medicine physician, has been recognized; measures to minimize it are being implemented. Radiation exposure to operating room and pathology personnel is very low; estimates of exposure to the surgeons hands are 0.2% of the annual whole body dose received by every human being from natural background and cosmic sources.

Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma detecting probe

Lymphoscintigraphy combined with intraoperative gamma-probe detection of sentinel lymph nodes in patients with inoperable early primary breast cancers is effective for staging the disease. The clinical alternative is axillary lymph node dissection, which is a far more invasive procedure and is accompanied by significant morbidity. Accuracy of staging is enhanced by immunohistochemical staining of micrometastases, which pathologists can easily perform for one to three sentinel lymph nodes, but not for 20 to 30 nodes, using axillary dissection procedure. Optimum methodology is presented for performing sentinel lymph node imaging and is important for accurate identification of sentinel node(s).

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/muCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 x 12.5 cm FOV) with a LEHR collimator (135 cpm/muCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.

Status of Sentinel Lymph Node for Breast Cancer

Long-awaited results from randomized clinical trials designed to test the validity of sentinel lymph node biopsy (SLNB) as replacement of axillary lymph node dissection (ALND) in management of early breast cancer have recently been published. All the trials conclude SLNB has survival rates comparable to those of ALND (up to 10 years in one study) and conclude SLNB has less morbidity than ALND. All the trials support replacing ALND with SLNB for staging in early breast cancer; all support SLNB as the standard of care for such cancer. The SLNB protocols used in the trials varied, and no consensus that would suggest a standard protocol exists. The results of the trials and of other peer-reviewed research do, however, suggest a framework for including some specific methodologies in accepted practice. This article highlights the overall survival and disease-free survival data as reported from the clinical trials. This article also reviews the status of SLN procedures and the following: male breast cancer, the roles of various imaging modalities (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, and ultrasound), ductal carcinoma in situ, extra-axillary SLNs, SLNB after neoadjuvant chemotherapy, radiation exposure to patients and medical personnel, and a new radiotracer that is the first to label SLNs not by particle trapping but by specific macrophage receptor binding. The proper Current Procedural Terminology (CPT) code for lymphoscintigraphy and SLN localization prior to surgery is 78195.

Immunohistochemical evaluation of sentinel lymph nodes in breast carcinoma patients.

Sentinel lymph node sampling has become an alternative to axillary lymph node dissection to provide prognostic and treatment information in breast cancer patients. The role of immunohistochemistry has yet to be established. A total of 241 sentinel lymph nodes (in 270 slides) from 91 patients with invasive carcinoma (73 ductal, 9 lobular, 8 mixed lobular/ductal, 1 NOS) were studied for presence of macrometastases (> 0.2 cm), identified in hematoxylin and eosin sections, and occult metastases (micrometastases [≤ 0.2 cm], clusters of cells, isolated carcinoma cells), identified only by immunohistochemistry. Intraoperative touch preparations, frozen sections, seven hematoxylin and eosin levels (L1–L7), and two AE1–3 cytokeratin immunohistochemistries (L1, L4–5) of the entire bisected or trisected sentinel lymph node were examined. Thirty-one (34%) patients had 50 positive sentinel lymph nodes. Twenty-six (33%) sentinel lymph nodes had metastatic carcinoma (11 macrometastases, 11 micrometastases, 3 clusters of cells, 1 isolated carcinoma cells) by touch preparations, frozen sections, and one hematoxylin and eosin (L1). Thirty-eight (43%) were positive by AE1–3 immunohistochemistry (L1) (11 macrometastases, 8 micrometastases, 13 clusters of cells, 6 isolated carcinoma cells), significantly more than by touch preparations, frozen sections, hematoxylin and eosin L1, or hematoxylin and eosin L2–7. Cytokeratin immunostain on L4–5 demonstrated 31 (34%) positive sentinel lymph nodes, a similar frequency to cytokeratin immunostain on L1. Size of sentinel lymph node metastasis did not correlate with size, histologic grade, or type of primary breast carcinoma. AE1–3 (L1) immunohistochemistry is highly sensitive in delineating sentinel lymph node metastasis, especially clusters of cells and isolated carcinoma cells. The prognostic significance of clusters of cells and isolated carcinoma cells and the value of AE1–3 immunohistochemistry on frozen sections need to be determined.

Comparison of camera-based 99mTc-MAG3 and 24-hour creatinine clearances for evaluation of kidney function.

OBJECTIVE The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Students t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearsons correlation coefficient. RESULTS The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearsons correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

Gamma cameras for intraoperative localization of sentinel nodes: technical requirements identified through operating room experience

Various nuclear medicine techniques are used for localization of sentinel lymph nodes (SLNs). Procedures that include high-quality preoperative imaging and skilled intraoperative use of a gamma counting probe are almost always successful. Those that involve only the intraoperative use of a gamma probe are generally less successful. For a variety of reasons, high-quality preoperative imaging is not possible at many institutions and thus many institutions use procedures that involve only intraoperative use of a gamma probe. It has been proposed that procedures involving intraoperative imaging be developed and evaluated. To better identify technical requirements for an intraoperative imaging system and protocol, five breast cancer patients were imaged intraoperatively, as well as preoperatively. The intraoperative imaging was performed using a small (127 mm /spl times/ 127 mm) field-of-view (FOV) gamma camera mounted on an articulating arm (Gamma Medica GammaCAM/OR). Intraoperative imaging was performed following administration of anesthesia and following preparation of a sterile surgical field about the involved breast. The camera and arm were draped in a sterile sheath, and the operators of the camera were attired in sterile surgical wear. Intraoperative images were acquired pre-incision and post-excision. Images were acquired for 2 to 3 minutes each. Members of the surgical/nuclear medicine team observed and assessed the ease or difficulty of the acquisitions of images. Conclusions included that a camera for SLN localization should exhibit low noise, should have very good shielding from all non-imaging directions, should have very low collimator penetration, and should have very good sensitivity at 140 keV. The system should have tools for flexible display windowing, convenient region-of-interest definition, and rapid image analysis. These features should be readily available and be easily controlled by the individual positioning the camera. The FOV should be at least 127 mm /spl times/ 127 mm but probably no larger than 200 mm /spl times/ 200 mm. A system should also have a means by which its camera can be easily repeatably positioned.

Clinical Intervention for Quality Improvement of Gastric-Emptying Studies

Prompted by clinical concerns for false-negative tests, we implemented a clinical intervention consisting of a training session and an image-based verification procedure to document homogeneous radioactivity distribution in the radiolabeled meal (egg substitute per the guideline). Methods: A technologist training session emphasized the importance of thorough mixing of 99mTc-sulfur colloid in the egg meal. For 6 mo after training, an image of the prepared mixed egg was acquired before patient ingestion. Consecutive gastric-emptying studies performed 6 mo before and after training were reviewed by 2 experienced physicians. Results: There were 7 abnormal and 44 normal studies before and 15 abnormal and 29 normal studies after training (P < 0.05). Subjective evaluations of images for meal-mixing quality by 2 readers correlated with each other and with an objective measure of expected gastric-emptying physiology (correlation coefficients, 0.54 and 0.38, respectively). Conclusion: The described clinical intervention improved the accuracy of our gastric-emptying studies by decreasing false-negative studies.

Harmonic subtraction for evaluating right ventricle ejection fraction from planar equilibrium radionuclide angiography

We report an initial investigation of a subtraction-based method to estimate right ventricle ejection fraction (RVEF) from ECG-gated planar equilibrium radionuclide angiography (ERNA) data. Twenty-six consecutive patients referred for scintigraphic evaluation of cardiac function prior to chemotherapy had ECG-gated first-pass (FP) imaging and ERNA imaging performed following the same radiotracer injection. RVEF was computed from FP images (RVEFFP) and separately from ERNA images (RVEFERNA). Standard methods for computing ejection fractions were used to obtain RVEFFP values. RVEFERNA values were obtained using harmonic subtraction of the left ventricular contribution from a biventricular region of interest contoured on the equilibrium images acquired in the shallow right anterior oblique projection. Clinically acquired chest CT data were used to derive information regarding the relative position of the left and right ventricle and about the presence of pulmonary artery enlargement. Computation of RVEFERNA was successful for each of the 26 patients. Computation of RVEFFP failed for four patients. For the 22 patients for which RVEF was computed using both methods, the average RVEFFP was 49% and the average RVEFERNA was 51%, with coefficients of variation of 11 and 7.5%, respectively. Low RVEFERNA values were associated with pulmonary artery dilation. Estimation of RVEFERNA, using a harmonic subtraction-based method of computation is clinically feasible and accurate in the patient population studied. The results support further investigation in patients with frank heart failure.