Immediate Plastic Surgery Intervention after Soft Tissue Sarcoma Resection: Examining Wound Healing, Readmission, and Reoperation.

Many orthopedic and surgical oncologists use a multidisciplinary approach to soft tissue sarcoma (STS) resection. This study assesses the role of immediate plastic surgeon involvement during index soft tissue sarcoma resection. Methods: Adult patients who underwent index STS resection between 2005 and 2018 were queried from an institutional database. Main outcomes analyzed were 90-day same-site reoperation, any-cause readmission, and wound healing complications. Univariate and multivariate logistic regression were used to identify risk factors. Additional evaluation was then performed for the following two cohorts: patients with and without plastic surgeon involvement. Results: In total, 228 cases were analyzed. Multivariate regression demonstrated the following predictors for 90-day wound-healing complications: plastic surgery intervention [OR = 0.321 (0.141-0.728), P = 0.007], operative time [OR = 1.003 (1.000-1.006), P = 0.039], and hospital length of stay [OR = 1.195 (1.004-1.367), P = 0.010]. For 90-day readmission, operative time [OR = 1.004 (1.001-1.007), P = 0.023] and tumor stage [OR = 1.966 (1.140-3.389), P = 0.015] emerged as multivariate predictors. Patients whose resection included a plastic surgeon experienced similar primary outcomes despite these patients having expectedly longer operative times (220 ± 182 versus 108 ± 67 minutes, P < 0.001) and hospital length of stay (3.99 ± 3.69 versus 1.36 ± 1.97 days, P < 0.001). Conclusions: Plastic surgeon involvement emerged as a significant protector against 90-day wound healing complications. Cases that included plastic surgeons achieved similar complication rates in all categories relative to cases without plastic surgery intervention, despite greater operative time, hospital length of stay, and medical complications.

Primary Desmoplastic Small Round Cell Tumor of the Femur: Case Report and Review of a Rare Intraosseous Malignancy.

Background: Desmoplastic small round cell tumors (DSRCT) are malignant neoplasms of young males arising most commonly in the abdominopelvic cavity, with a subset originating from extra-abdominal soft tissues. As either primary or metastatic lesions, they are rare in intraosseous sites. Case Presentation: We describe the fifth report of primary DSRCT of bone. A healthy 18-year old male presented with a blastic, 17 cm lesion within the left distal femur, suspicious for osteosarcoma or Ewing sarcoma. Subsequent biopsy revealed nests of small round blue cells infiltrating through a desmoplastic stroma. These cells were diffusely positive for epithelial markers, with paranuclear staining for desmin and focal reactivity with NSE. Break-apart FISH revealed a rearrangement in EWSR1, and RNA fusion panel confirmed WT1 as its partner in the pathognomonic t(11;22)(p13;q12) rearrangement. PET/CT showed widespread metastatic disease to visceral and bony sites. Conclusions: Due to their rarity as well as clinicopathologic and immunomorphologic overlap, primary intraosseous DSRCT can create diagnostic challenges with the more frequently encountered tumors of bone.

Metabotropic glutamate receptor-1 as a novel target for the antiangiogenic treatment of breast cancer.

Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. In addition to cancer cells, brain endothelial cells express mGluR1. In light of these studies, and because angiogenesis is both a prognostic indicator in cancer correlating with a poorer prognosis and a potential therapeutic target, we explored a potential role for mGluR1 in mediating endothelial cell (EC) proliferation and tumor-induced angiogenesis. GRM1 and mGluR1 were detected in various types of human ECs and, using mGluR1-specific inhibitors or shRNA silencing, we demonstrated that EC growth and Matrigel tube formation are dependent on mGluR1 signaling. In addition, loss of mGluR1 activity leads to reduced angiogenesis in a murine Matrigel sponge implant model as well as a murine tumor model. These results suggest a role for mGluR1 in breast cancer as a pro-angiogenic factor as well as a mediator of tumor progression. They also suggest mGluR1 as a potential new molecular target for the anti-angiogenic therapy of breast cancer.

Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer.

Metabotropic glutamate receptors are G-protein-coupled receptors normally expressed in the central nervous system where they mediate neuronal excitability, synaptic plasticity, and feedback inhibition of neurotransmitter release. However, recent data suggest that these receptors are also expressed and functional in some cancers, most notably melanoma. We detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in triple negative breast cancer cells and evaluated its role in regulating the pro-proliferative phenotype of these cells. mGluR1 inhibitors (Riluzole or BAY36-7620) inhibited the proliferation of triple negative breast cancer cells in a time- and dose-dependent manner and this inhibition correlated with increased apoptosis as demonstrated by increase in PARP cleavage products and Annexin V staining. mGluR1 knockdown using Lentiviral constructs expressing shRNA targeting GRM1 also inhibited proliferation compared to non-silencing controls. In addition, treatment of mice bearing MDA-MB-231 xenografts with Riluzole or BAY36-7620, by intraperitoneal injection, resulted in a significant reduction in tumor volume of up to 80%. Moreover, Riluzole was effective against triple negative breast cancer xenografts in mice at doses equivalent to those currently being used in humans for the treatment of amyotrophic lateral sclerosis. Our observations implicate mGluR1 and glutamate signaling as a promising new molecular target for the treatment of breast cancer. Even more promising, Riluzole, because it is an oral drug that can be administered with low toxicity, represents a promising approach in the treatment of triple negative breast cancer.