Evaluation of traditional targeted axillary dissection eligibility criteria for node-positive breast cancer after neoadjuvant chemotherapy in a prospective multicenter registry.

INTRODUCTION: Targeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. METHODS: Data was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. RESULTS: A total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00-11.93, p = 0.42; N stage: 95% CI 0.00-8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00-5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72-52.49, p = 0.13; radiotracer vs dual tracer 0.04-20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00-10.61, p = 0.38). CONCLUSIONS: TAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.

Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.

PURPOSE: Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. MATERIALS AND METHODS: Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. RESULTS: Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p < 0.05). Synovial fluid MMP activity and PGE2 concentrations were positively correlated in meniscus tear subjects (R = 0.83, p < 0.0001). In meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p < 0.05). Subjects with complex meniscus tears had higher synovial fluid MMP-10 (p < 0.05) and reduced serum TNFα and IL-8 (p < 0.05) compared to other tear types. CONCLUSIONS: Given the degradative and pro-inflammatory roles of MMP activity and PGE2, these molecules may alter the biochemical environment of the joint. Our findings suggest that modulation of PGE2 signaling, MMP activity, or both following a meniscus injury may be targets to promote meniscus repair and prevent OA development.

In vivo cartilage strain increases following medial meniscal tear and correlates with synovial fluid matrix metalloproteinase activity.

Meniscal tears are common injuries, and while partial meniscectomy is a frequent treatment option, general meniscus loss is a risk factor for the development of osteoarthritis. The goal of this study was to measure the in vivo tibiofemoral cartilage contact patterns in patients with meniscus tears in relation to biomarkers of cartilage catabolism in the synovial fluid of these joints. A combination of magnetic resonance imaging and biplanar fluoroscopy was used to determine the in vivo motion and cartilage contact mechanics of the knee. Subjects with isolated medial meniscus tears were analyzed while performing a quasi-static lunge, and the contralateral uninjured knee was used as a control. Synovial fluid was collected from the injured knee and matrix metalloproteinase (MMP) activity, sulfated glycosaminoglycan, cartilage oligomeric matrix protein, prostaglandin E2, and the collagen type II cleavage biomarker C2C were measured. Contact strain in the medial compartment increased significantly in the injured knees compared to contralateral control knees. In the lateral compartment, the contact strain in the injured knee was significantly increased only at the maximum flexion angle (105°). The average cartilage strain at maximum flexion positively correlated with total MMP activity in the synovial fluid. These findings show that meniscal injury leads to loss of normal joint function and increased strain of the articular cartilage, which correlated to elevated total MMP activity in the synovial fluid. The increased strain and total MMP activity may reflect, or potentially contribute to, the early development of osteoarthritis that is observed following meniscal injury.