Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas.

The cancer stem cell (CSC) hypothesis postulates that heterogeneous human cancers harbor a population of stem-like cells which are resistant to cytotoxic therapies, thus providing a reservoir of relapse following conventional therapies like chemotherapy and radiation (RT). CSCs have been observed in multiple human cancers, and their presence has been correlated with worse clinical outcomes. Here, we sought to evaluate the impact of drug dosing of the multi-tyrosine kinase inhibitor, sorafenib, on CSC and non-CSCs in soft tissue sarcoma (STS) models, hypothesizing differential effects of sorafenib based on dose and target cell population. In vitro, human cancer cell lines and primary STS from surgical specimens were exposed to escalating doses of sorafenib to determine cell viability and expression of CSC marker aldehyde dehydrogenase (ALDH). In vivo, ALDHbright CSCs were isolated, exposed to sorafenib, and xenograft growth and survival analyses were performed. We observed that sarcoma CSCs appear to paradoxically respond to the tyrosine kinase inhibitor sorafenib at low doses with increased proliferation and stem-like function of CSCs, whereas anti-viability effects dominated at higher doses. Importantly, STS patients receiving neoadjuvant sorafenib and RT on a clinical trial (NCT00864032) showed increased CSCs post therapy, and higher ALDH scores post therapy were associated with worse metastasis-free survival. These data suggest that low-dose sorafenib may promote the CSC phenotype in STS with clinically significant effects, including increased tumor growth and higher rates of metastasis formation in sarcoma patients.

Financial Decisions and Reopening a Practice During the COVID-19 Pandemic: A Survey of California Plastic Surgeons.

BACKGROUND: On March 11, 2020, the World Health Organization declared COVID-19 as a global pandemic. As a response, the United States shut down public gatherings and businesses in an effort to quarantine. This included the stopping of elective operations, which greatly affected plastic surgeons and their practices during the initial shutdown. OBJECTIVES: We aim to study the early impact of COVID-19 on the financial implications and practice patterns of plastic surgeons in the state of California during the initial shutdown of elective surgery and provide guidelines for effective management during future crises. METHODS: A 20-question survey was sent using Qualtrics XM software to 851 surgeon members of the California Society of Plastic Surgeons. The survey was open from May 13, 2020, to May 29, 2020. Standard statistical analysis was completed to compare private practice and nonprivate practice plastic surgeons. RESULTS: We had a total of 140 respondents to our survey for a 16.5% response rate. The majority (77.1%) of the respondents were in a private practice setting. Private practice plastic surgeons reported a higher financial impact with a 79% reduction in financial income compared with nonprivate practice plastic surgeons at a 37% reduction (P < 0.0001). Additionally, private practice plastic surgeons demonstrated a higher reduction in case volume and were more likely to lay off or furlough staff, close their practice, and apply for loans (P < 0.001). CONCLUSIONS: Our survey study showed that private practice plastic surgeons in the state of California faced the most financial hardship during the early shutdown of the COVID-19 pandemic. It serves as a valuable snapshot in our economic history and depicts the heavy financial impact of the stopping of elective surgery. Since the reopening of practices, new guidelines have been implemented to maintain safe elective surgery while the pandemic continues. Further follow-up studies on both the state and national level need to be completed to see the continued financial effects on private and nonprivate plastic surgery practices since the reopening and resumption of elective surgery.

Speech and Audiology Outcomes After Single-Stage Versus Early 2-Stage Cleft Palate Repair.

PURPOSE: The timing and management of patients with cleft palates have been controversial. Early soft palate closure at the time of cleft lip repair followed by hard palate closure at a second stage has been hypothesized to improve speech and audiology outcomes. This study compares cleft palate patients who have undergone single-stage versus 2-stage cleft palate repairs and the outcomes on speech and hearing. METHODS: A retrospective chart review identified patients with diagnosis of cleft lip with complete cleft palate who underwent either single or 2-stage repair from 2006 to 2012. Data collected included age at each surgery, necessity of further speech surgery for velopharyngeal insufficiency, frequency of tympanostomy tube placement, presence of hearing loss, and speech assessment data graded per the validated Americleft speech scale. RESULTS: A total of 84 patients were identified and subdivided into groups of single-stage and 2-stage repair. The mean age at the time of single-stage palate repair was 13.3 months. For the 2-stage group, the mean ages were 4.2 and 11.8 months for the soft palate and hard palate repairs, respectively. Comparing the single-stage versus 2-stage palate repairs, there was no significant difference in all speech parameters including hypernasality, hyponasality, nasal air emission, articulation, expressive language, receptive language, speech intelligibility, and speech acceptability for both unilateral and bilateral cleft lip/palate patients. Two-stage repair was associated with increased number of tympanostomy tube placement compared with single-stage repair (relative risk, 1.74; P = 0.009), and the first set of tubes was performed at a statistically significantly younger age, 4.5 months in the 2-stage repair compared with 16.9 months in the single-stage (P = 0.012) with 87.5% performed with first stage of repair. However, there was no difference in the types, degrees of hearing loss, or the presence of at least mild conductive hearing loss at latest follow-up audiograms between the groups. CONCLUSIONS: There was no significant benefit with respect to speech or hearing outcomes between single-stage and 2-stage cleft palate repairs. This advocates for surgeon and family preference in the timing of cleft palate repair.

The Association of Liposomal Bupivacaine on Opioid Consumption in the Pediatric Alveolar Cleft Population.

Surgical infiltration of liposomal bupivacaine in the adult population has been shown to decrease perioperative use of opioids, but there have been few studies conducted in the pediatric surgical population. The authors' objective was to assess the effect of liposomal bupivacaine on opioid reduction in the pediatric alveolar cleft population. The authors hypothesized that the use of surgical site infiltration with liposomal bupivacaine would be associated with decreased post-operative opioid requirements following alveolar bone grafting.The authors performed a retrospective cohort study at a tertiary craniofacial center. Forty-four pediatric patients undergoing alveolar bone grafting from November 2016 to December 2018 by the 2 craniofacial surgeons at Rady Children's Hospital were included in the study. Surgical site infiltration with liposomal bupivacaine was performed and the amount of oral morphine equivalents administered within the first 24 hours was measured.Patients in the liposomal bupivacaine cohort required 12.0 mg OME less than those patients who received standard bupivacaine or 1% lidocaine. When controlling for age, sex, weight, laterality, and harvest technique, multivariable linear regression analysis demonstrated a difference of 15.7 mg OME in favor of the LB cohort (P = 0.0006).The authors' study revealed that intraoperative surgical site infiltration of liposomal bupivacaine was associated with decreased post-operative opioid requirements following alveolar bone grafting. It should be considered as an effective part of multimodal pain therapy in the pediatric surgical population.

Utility of a Team-Based Multimodal Opioid Reduction Protocol for the Pediatric Plastic Surgery Population.

Opioid use can cause significant adverse side effects with increased propensity toward both short- and long-term complications in the pediatric population. We present a multifaceted opioid reduction protocol based on physician and care team member education. The strategy was designed to alter prescribing practices, improve preoperative and postoperative patient education, increase the use of nonnarcotic pain control modalities, and improve coordination of opiate reduction strategies for all team members participating in patient care. We present the utility of this strategy in limiting postoperative narcotic use in the pediatric plastic surgery population.A prospective study with historical controls was conducted to evaluate pediatric patients undergoing elective pediatric plastic surgery procedures at 3-month intervals in 2016, 2017, and 2018. In the final year, the dedicated opiate reduction protocol was implemented before the data collection period, and results were compared with the prior 2 collection periods. The primary outcomes were total days and doses of outpatient narcotics prescribed after surgery.The median days (quartiles) of opioids prescribed in 2016, 2017, and 2018 cohorts were 1.5 (1.1, 2.5) days, 1.5 (1.4, 2.5) days, and 0.8 (0, 1.6) days, respectively. The median doses (quartiles) of opioids prescribed in 2016, 2017, and 2018 cohorts were 6.3 (6, 10), 6.0 (5.7, 15.0), and 4.2 (0, 6.2) doses, respectively. There were statistically significantly less days and doses of opioids prescribed in the 2018 cohort when compared with the 2016 (P < 0.0001) and 2017 (P < 0.0001) cohorts.A multimodal opioid reduction protocol was successfully implemented for the pediatric plastic surgery population. Patients were able to shorten the duration of narcotic prescription upon discharge with the use of a multidisciplinary team approach.