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.

Concurrent management of lymphedema and breast reconstruction with single-stage omental vascularized lymph node transfer and autologous breast reconstruction: A case series.

INTRODUCTION: The omentum has gained recent popularity in vascularized lymph node transfers (VLNT) as well as its novel use as a free flap for autologous breast reconstruction. The omentum has multiple unique advantages. It can be harvested laparoscopically or in an open fashion when utilized with abdominally-based free flaps. Additionally, it can be split into multiple flaps for simultaneous autologous breast reconstruction with VLNT or for multiple sites of VLNT. We present the safe and advantageous use of the omentum for VLNT with simultaneous autologous breast reconstruction in a series of patients. METHODS: From the years 2019-2022, patients who underwent breast reconstruction with deep inferior epigastric artery perforator (DIEP) or muscle sparing tram (MS-TRAM) flaps with concurrent omental VLNT through a mini-laparotomy or breast reconstruction with Omental Fat-Augmented Free Flap (O-FAFF) with concurrent laparoscopic harvesting of omental VLNT were studied. Patient demographics included age, gender, comorbidities, prior radiation or chemotherapy, body mass index, complications, hospital length of stay, and surgical outcomes. RESULTS: A total of seven patients underwent omental VLNT with breast reconstruction for a total of 12 breasts and eight limbs treated. Three of the patients underwent autologous breast reconstruction using omental free flap. The mean age was 52.3 (range 40-75) years and mean body mass index (BMI) was 29.3 (range 23-38) kg/m2 . The flap survival rate was 100%. All the patients had successful reduction of extremity circumference and improvement of symptoms. The range of follow-up was 5 to 19 months, with an average follow-up of 14.6 months. There was only one complication among our 7 patients: a patient with a BMI of 38 developed a post-surgical abdominal wound treated with local wound care. Otherwise, post-operative courses were uneventful, and no further complications were reported. CONCLUSION: We demonstrate here additional evidence to the growing body of literature of the versatility and safety of the omentum to be utilized as an independent tool for surgical treatment of lymphedema as well as its simultaneous use with autologous breast reconstruction.

Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop: A Single Institution's Experience.

SUMMARY: Several minority groups and students without home plastic surgery programs remain underrepresented in plastic surgery. To address these barriers, our division created the Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop. Students meeting at least one of the following eligibility criteria were invited in fall of 2020: medical student in years 1 though 3 or a research year who is (1) underrepresented in medicine, including African American, Hispanic/Latinx, Native American, Pacific Islander; (2) lesbian, gay, bisexual, transgender, or queer (LGBTQ); (3) first-generation low-income; or (4) does not have a plastic surgery residency program associated with their medical school. Students participated in quarterly meetings with their resident mentor and the annual hands-on workshop. The workshop was held on March 20, 2020, with both virtual and in-person participants. It included various didactic lectures, a suture laboratory, a resident panel, a social lunch hour, and extremity and head cadaver dissections with fracture plating. Twenty-four students attended the workshop. The course was rated 9.4 of 10 by students. The top met goals were gaining didactic plastic surgery knowledge (100%), exposure to a plastic surgery residency program (100%), resources to help overcome minority-specific barriers (96%), and technical skills such as suturing (96%). At the conclusion of the workshop, students had a significant increase in confidence in various aspects of plastic surgery knowledge and technical skills. The Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop demonstrated preliminary success in providing support for students underrepresented in medicine and students without home programs.

Topical Dimethyl Sulfoxide for Congested Nipple-areolar Complexes in Breast Surgery: A Pilot Study.

Necrosis of the nipple-areolar complex (NAC) is a major complication of breast surgery that most commonly results from venous congestion. Several conservative rescue therapies have been proposed for relieving NAC congestion, but each carries certain drawbacks, including cost and side effect profile. In this study, we evaluated the effectiveness of topical dimethyl sulfoxide (DMSO), an inexpensive compound with vasodilatory, free radical scavenging, and antiinflammatory properties in rescuing congested NACs. Methods: We conducted a review of all 15 patients treated with DMSO for NAC congestion at our institution between May 2019 and October 2020. DMSO was applied in liquid form on a soaked gauze pad in the hospital; patients were instructed to apply a DMSO cream to the NAC twice a day following discharge. Patient characteristics and data related to DMSO treatment and NAC healing were compared via univariate analysis. Results: Eighteen congested NACs from 15 patients who underwent mastectomy, breast reduction, mastopexy, or breast reconstruction were treated with DMSO. Of the 18 treated NACs, 15 healed with DMSO treatment alone. The average length of DMSO treatment was 9.4 ± 8.5 days (mean ± standard deviation); NAC healing took place over 9.9 ± 9.6 days. There were no complications related to DMSO treatment. Conclusions: This pilot study shows that DMSO may be an effective topical treatment for NAC congestion following breast surgery. Given its low cost, ease of application, and lack of side effects, future studies should prospectively compare DMSO against other topical treatments, like nitroglycerin ointment.

Glabellar Botulinum Toxin Injection Improves Depression Scores: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression is a leading cause of disability worldwide. Preliminary evidence suggests that glabellar onabotulinumtoxinA injections improve depression scores with few side effects compared to current first-line antidepressant medications. The authors' review reports on these studies, hypothesizing that glabellar onabotulinumtoxinA injections can be an alternative safe and effective treatment for depression. METHODS: A systematic review and meta-analysis of the relevant literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Cochrane Library, Embase, and Scopus databases were searched in August of 2020 using the keywords ["botox" OR "botulinum"] AND ["mood" OR "depression"] for articles published between 1980 and 2020. Prospective studies and randomized controlled trials on the use of glabellar onabotulinumtoxinA injections for the primary purpose of treating depression were considered. The primary endpoint for the meta-analysis was the mean difference in primary depression scores after treatment, along with a second endpoint of the standardized mean difference in depression scores among treated patients including all nine studies. RESULTS: Of the 499 reviewed articles, nine studies were included that reported improvement in mean depression scores from baseline. All five randomized controlled trials reported an improvement in mean depression scores at 6 weeks after treatment, with a weighted average change of -8.39 points ( p < 0.0001). The aggregate standardized mean difference from baseline to the primary endpoint across all nine prospective studies was -1.61 SD ( p < 0.0001). CONCLUSION: Meta-analysis and systematic review of the included studies provide support for an antidepressant effect of glabellar onabotulinumtoxinA injections.

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.

Rectovaginal Fistula Repair 1 Year Later: Lessons Learned.

INTRODUCTION: Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for repair exist, and refinements in techniques can lead to "successful" outcomes. Review of the literature demonstrates that outcomes studies are scarce and mostly limited to comments on closure rate. We have experienced "success" in our own series with 100% closure rate, regardless of fistula etiology and comorbidities (radiation, inflammation, etc). However, long-term outcomes, including various complications and quality of life changes, have previously been underreported. METHODS: Critical analysis of various outcomes after fistula repair in 14 patients was performed. Patients were surveyed and interviewed with regard to problems before and after fistula repair to obtain objective data focusing on their experience and outcomes. Conclusions are based on physician assessment and patient surveys 1 year after fistula repair and at least 6 months after ostomy reversal and are discussed within the context of data from the literature. RESULTS: Overall satisfaction rate after repairs was high. All patients would undergo attempt at repair again regardless of complications or functional changes (not present before repair). After repair, sexual dyspareunia affected 5 patients (36%); however, most abstained from sexual activity when their RV fistula became apparent. No patient admitted to dyspareunia before the development of their RV fistula. Anal sphincter and defecation function, as well as stool continence, were judged by surgeons and patients uniformly as adequate. However, 3 patients (21%) complained of intermittent problems with urination. A new/different type of pain affected 2 of 4 patients with Crohn disease. One of these patients subsequently developed a new postsphincteric RV fistula. Another patient noted new intermittent vaginal discharge after ostomy reversal, and magnetic resonance imaging suggested a residual fistula, which was not seen on follow-up sigmoidoscopy and "Blue Dye Test." CONCLUSIONS: We previously reported on algorithms for repair and refinements in techniques for "successful" repair of RV fistulas with zero recurrence rate. Long-term follow-up indicates, however, that although the overall satisfaction rate after surgery is high, true "success," defined as permanent fistula closure, is not necessarily problem free. Long-term morbidity and the management of other unique sequelae and problems are underreported.

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.