Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

BACKGROUND: Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. METHODS: A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. RESULTS: A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. CONCLUSION: [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

A receptor-targeted fluorescent radiopharmaceutical for multireporter sentinel lymph node imaging.

PURPOSE: To determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection. MATERIALS AND METHODS: The animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m (99mTc)-labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99mTc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99mTc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test. RESULTS: In vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L±0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6×10(3) counts·sec(-1)·µW(-1) per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P=.005 to P=.042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation. CONCLUSION: The multireporter probe 99mTc-labeled Cy7 tilmanocept exhibits in vitro and in vivo receptor-binding properties for successful receptor-targeted SLN mapping with nuclear and optical imaging.

Minimally invasive and robotic-assisted thymus resection.

Thymectomy for thymoma has traditionally been performed through a transsternal approach because of the excellent exposure that that the median sternotomy provides. Minimally invasive alternatives, such as transcervical thymectomy, video-assisted thymectomy, and robotic thymectomy, have not been extensively evaluated for this disease process. It is uncertain which patients may benefit from minimally invasive approaches and data regarding the oncologic effectiveness of these techniques remains to be established. However, given the excellent capability of these techniques to perform a complete and extensive thymectomy, there does appear to be a role for minimally invasive thymectomy in the treatment of thymoma.

The prevalence of obesity and postoperative complications in a Veterans Affairs Medical Center general surgery population.

Patients who are obese are believed to be at greater risk of developing intraoperative and postoperative complications than their nonobese counterparts. Many studies have shown that there is a higher prevalence of obesity among the Veterans Affairs patient population. We performed a retrospective review of 941 patients presenting to a single Veterans Affairs Medical Center. We aimed to determine the incidence of obesity among the Veterans Affairs Medical Center general surgery patient population as well to compare the frequency of postoperative complications between patients who are obese and nonobese patients undergoing elective general surgery. Body mass index was calculated for all patients; of the 941 patients seen in the clinic, 547 underwent elective surgery. Thirty-three per cent of all clinic patients had a body mass index greater than 30 kg/m2. Twenty-eight per cent of patients who underwent surgery had a body mass index greater than 30 kg/m2. Postoperative complications developed among 5.5 per cent of all surgical patients; 23.3 per cent were obese and 76.7 per cent were nonobese. There was no statistically significant difference between these two groups (P = 0.54). This study illustrates the increased prevalence of obesity among the Veterans Affairs Medical Center general surgery patient population. In addition, our study suggests that obesity is not an independent risk factor for postoperative complications in patients undergoing elective general surgery.

Case report and review of the literature total endovascular repair of acute ascending aortic rupture: a case report and review of the literature.

Thoracic aortic endografting has been successfully implemented to treat aneurysmal disease of the distal aortic arch and descending thoracic aorta. Although there are reports of ascending aortic endovascular interventions, the total endovascular repair of a ruptured ascending aorta secondary to a Type A dissection has not been described. We report the case of a 77-year-old patient who presented with a ruptured ascending aortic aneurysm secondary to degeneration of a Stanford type A aortic dissection. His surgical history was significant for orthotropic heart transplant 19 years prior. The dissection, aneurysm, and rupture occurred in the native aorta distal to the ascending aortic suture line. At presentation, he was hemodynamically unstable with a right hemothorax. We placed 3 Medtronic Talent Thoracic Stent Graft devices (Medtronic Inc, Minneapolis, MN) across the suture line in the ascending aorta, excluding the rupture. The patient survived and has been followed to 25 months.

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a "2-day" protocol.

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [(99m)Tc]sulfur colloid (TcSC) using a "2-day" protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of (99m)Tc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18+/-1.09 h compared to 57.4+/-92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5+/-1.7%) and TcSC (3.5+/-3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [(99m)Tc]sulfur colloid and persistent SLN accumulation for at least 24 h.

Forearm interosseous membrane trauma: MRI diagnostic criteria and injury patterns.

OBJECTIVE: Define criteria for interosseous membrane (IOM) injury diagnosis using MRI, and characterize patterns of IOM disruption following forearm trauma. Our hypothesis is that most IOM injuries occur along the ulnar insertion, and MRI should be obtained following forearm trauma to assess IOM competency. DESIGN: Sixteen cadaver forearms were subjected to longitudinal impact trauma. Prior to and following injury, MR images were examined by a board-certified musculoskeletal radiologist using pre-defined criteria for determining IOM integrity. Each specimen was dissected and the viability/pattern of injury examined. The MRI and dissection results were compared using a double-blinded methodology. RESULTS: Eight of the 16 specimens demonstrated IOM trauma. Seven specimens demonstrated complete IOM disruption from the ulnar insertion, and one revealed a mid-substance tear with intact origin and insertion. The dorsal oblique bundle was disrupted in four specimens. MRI analysis identified IOM injury in seven of the eight forearms. The injury location was correctly identified in six specimens when compared to dissection observations. MRI determination of IOM injury demonstrated a positive predictive value of 100%, a negative predictive value of 89%, a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Our findings demonstrate the accuracy of MRI in identifying IOM disruption, and its ability to localize specific injuries in a clinically relevant model of forearm trauma. The injury patterns demonstrated most lesions occurred along the IOM's ulnar insertion, and in half of the injured specimens there was concomitant dorsal oblique bundle disruption.