Magnetic Seed vs Guidewire Breast Cancer Localization With Magnetic Lymph Node Detection: A Randomized Clinical Trial.

Importance: Guidewires have been the standard for breast lesion localization but pose operative and logistic challenges. Paramagnetic seeds have shown promising results, but to the authors' knowledge, no randomized comparison has been performed. Objective: To determine whether the combination of a paramagnetic seed and superparamagnetic iron oxide (SPIO) is equivalent to guidewire and SPIO for breast cancer localization and sentinel lymph node detection (SLND). Design, Setting, and Participants: This was a phase 3, pragmatic, equivalence, 2-arm, open-label, randomized clinical trial conducted at 3 university and/or community hospitals in Sweden from May 2018 to May 2022. Included in the study were patients with early breast cancer planned for breast conservation and SLND. Study data were analyzed July to November 2022. Interventions: Participants were randomly assigned 1:1 to a paramagnetic seed or a guidewire. All patients underwent SLND with SPIO. Main Outcomes and Measures: Re-excision rate and resection ratio (defined as actual resection volume / optimal resection volume). Results: A total of 426 women (median [IQR] age, 65 [56-71] years; median [IQR] tumor size, 11 [8-15] mm) were included in the study. The re-excision rate was 2.90% (95% CI, 1.60%-4.80%), and the median (IQR) resection ratio was 1.96 (1.15-3.44). No differences were found between the guidewire and the seed in re-excisions (6 of 211 [2.84%] vs 6 of 209 [2.87%]; difference, -0.03%; 95% CI, -3.20% to 3.20%; P = .99) or resection ratio (median, 1.93; IQR, 1.18-3.43 vs median, 2.01; IQR, 1.11-3.47; P = .70). Overall SLN detection was 98.6% (95% CI, 97.1%-99.4%) with no differences between arms (203 of 207 [98.1%] vs 204 of 206 [99.0%]; difference, -0.9%; 95% CI, -3.6% to 1.8%; P = .72). More failed localizations occurred with the guidewire (21 of 208 [10.1%] vs 4 of 215 [1.9%]; difference, 8.2%; 95% CI, 3.3%-13.2%; P < .001). Median (IQR) time to specimen excision was shorter for the seed (15 [10-22] minutes vs 18 [12-30] minutes; P = .01), as was the total operative time (69 [56-86] minutes vs 75.5 [59-101] minutes; P = .03). The experience of surgeons, radiologists, and surgical coordinators was better with the seed. Conclusions and Relevance: The combination of SPIO and a paramagnetic seed performed comparably with SPIO and guidewire for breast cancer conserving surgery and resulted in more successful localizations, shorter operative times, and better experience. Trial Registration: ISRCTN.org Identifier: ISRCTN11914537.

A Comparison of Skin Staining after Sentinel Lymph Node Biopsy in Women Undergoing Breast Cancer Surgery Using Blue Dye and Superparamagnetic Iron Oxide Nanoparticle (SPIO) Tracers.

Superparamagnetic iron oxide nanoparticles (SPIO) are a tracer for sentinel lymph node (SLN) detection. In a preplanned secondary analysis of a prospective clinical trial (SentiDose) we reported on skin staining after SPIO and blue dye (BD) injections. For SPIO, either a 1.5 mL retroareolar injection on the day of surgery or a 1.0 mL peritumoral/retroareolar injection 1-7 days before surgery was given. A 1.0 mL sub-/intradermal periareolar injection of BD was also administered to all these women. Staining was then assessed at 6, 12 and 24 months after surgery. A total of 270 women received SPIO and were operated on with breast-conserving surgery. Of these, 204 women also received BD. A total of 58 (21.5%) women had an SPIO stain 6 months postoperatively with a median size of 6.8 cm2 (p = 0.56), while 51 (25.0%) had a BD stain with a median size of 8.5 cm2 (p = 0.93). The incidence and size of SPIO and BD staining decreased over time reciprocally. At 24 months, the incidence and median size of SPIO was 23 (8.6%) and 4 cm2, respectively. For BD, the incidence was 14 (6.3%, p = 0.13), and the median size was 3.5 cm2 (p = 0.18). There was, therefore, no statistically significant difference in the incidence or size of skin staining between SPIO and BD over time.

Magnetic-Guided Axillary UltraSound (MagUS) Sentinel Lymph Node Biopsy and Mapping in Patients with Early Breast Cancer. A Phase 2, Single-Arm Prospective Clinical Trial.

Lymph Node Dissection (SLND) is standard of care for diagnosing sentinel lymph node (SLN) status in patients with early breast cancer. Study aim was to determine whether the combination of Superparamagnetic iron oxide nanoparticles (SPIO) MRI-lymphography (MRI-LG) and a Magnetic-guided Axillary UltraSound (MagUS) with biopsy can allow for minimally invasive, axillary evaluation to de-escalate surgery. Patients were injected with 2 mL of SPIO and underwent MRI-LG for SN mapping. Thereafter MagUS and core needle biopsy (CNB) were performed. Patients planned for neoadjuvant treatment, the SLN was clipped and SLND was performed after neoadjuvant with the addition of isotope. During surgery, SLNs were controlled for signs of previous biopsy or clip. The primary endpoint was MagUS SLN detection rate, defined as successful SLN detection of at least one SLN of those retrieved in SLND. In 79 patients, 48 underwent upfront surgery, 12 received neoadjuvant and 19 had recurrent cancer. MagUS traced the SLN in all upfront and neoadjuvant cases, detecting all patients with macrometastases (n = 10). MagUS missed only one micrometastasis, outperforming baseline axillary ultrasound AUS (AUC: 0.950 vs. 0.508, p < 0.001) and showing no discordance to SLND (p = 1.000). MagUS provides the niche for minimally invasive axillary mapping that can reduce diagnostic surgery.

Alkalosis in Critically Ill Patients with Severe Sepsis and Septic Shock.

INTRODUCTION: Although metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock. METHODS: This is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS). RESULTS: Metabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset >48 hours) were the only significant predictor of increased ICU length of stay. CONCLUSION: Metabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay.