A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model

Purpose

TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model.

Methods

Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically.

Results

No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p?=?0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p?=?0.005).

Conclusions

TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

     

Trends in Lumpectomy and Oncoplastic Breast-Conserving Surgery in the US, 2011–2016

Background

Oncoplastic breast surgery aims to optimize efficacy of surgical resection and cosmesis to maximize patient satisfaction; however, despite the benefits, oncoplastic techniques have not been widely adopted in the US. This study examined trends in the incidence of lumpectomy (partial mastectomy) with or without oncoplastic techniques from 2011 to 2016.

Methods

This was a retrospective analysis of claims from the Optum Clinformatics database (January 2010–March 2017). Female patients with no history of breast surgery in the prior year were categorized into three independent cohorts: isolated lumpectomy (Lx), lumpectomy with tissue transfer (LxTT), or lumpectomy with mammaplasty and/or mastopexy (LxMM). Oncoplastic techniques (in cohorts two and three) were performed at either time of the initial lumpectomy or during 90-day follow-up.

Results

Overall, 19,253 patients met the inclusion criteria (91.1% Lx, 5.2% LxTT, and 3.7% LxMM). Significantly fewer patients with Lx had a family history of breast cancer compared with patients with oncoplastic techniques (26.4% vs. 33.7% and 37.9%, respectively; p?<?0.001). The incidence of Lx declined significantly from 2011 (92.9%) to 2016 (88.1%), while LxTT and LxMM increased from 4.2 to 7.2% and 2.8 to 4.7%, respectively (both p?<?0.001). The greatest utilization of oncoplastic techniques was observed in the Pacific census division (19.2%), while lowest utilization was in the East South Central division (3.2%; p?<?0.001).

Conclusions

While increased adoption of oncoplastic techniques was observed, the compound annual growth rate remained below 10% and varied significantly by region. Further adoption of oncoplastic techniques is necessary to improve cosmetic outcomes and patient satisfaction following breast-conserving surgery.

     

Ultrasound‐guided wire localization of focal ductal dilatation in the evaluation and treatment of pathologic nipple discharge

Patients presenting with pathologic nipple discharge (PND) often pose a diagnostic and therapeutic challenge. We used ultrasound to identify focal ductal dilatation—hypothesized to be a radiographic manifestation of the causative lesion—in patients with PND and no relevant clinical or radiographic findings. Twenty‐two excisions guided by ultrasound wire localization of focal duct dilation were performed. Surgical pathology revealed papilloma in 20 cases (91%); atypia or carcinoma was detected in 7 cases (32%). The ultrasound finding of focal duct dilatation enables excision of otherwise occult though clinically significant lesions and is worthy of further study.