Introduction: Soft-tissue reconstruction of the scalp has traditionally been challenging in oncologic patients. Invasive tumors can compromise the calvarium, necessitating alloplastic cranioplasty. Titanium mesh is the most common alloplastic material, but concerns of compromise of soft-tissue coverage have introduced hesitancy in utilization. The authors aim to identify prognostic factors associated with free-flap failure in the context of underlying titanium mesh in scalp oncology patients. Methods: A retrospective review (2010–2018) was conducted at a single center examining all patients following oncologic scalp resection who underwent titanium mesh cranioplasty with free-flap reconstruction following surgical excision. Patient demographics, comorbidities, ancillary oncological treatment information were collected. Operative data including flap type, post-operative complications including partial and complete flap failure were collected. Results: A total of 16 patients with 18 concomitant mesh cranioplasty and free-flap reconstructions were identified. The majority of patients were male (68.8%), with an average age of 70.5 years. Free-flap reconstruction included 15 ALT flaps (83.3%), 2 latissimus flaps (11.1%), and one radial forearm flap (5.5%). There were three total flap losses in two patients. Patient demographics and comorbidities were not significant prognostic factors. Additionally, post-operative radiation therapy, ancillary chemotherapy, oncological histology, tumor recurrence, and flap type were not found to be significant. Pre-operative radiotherapy was significantly associated with flap failure (P < 0.05). Conclusion: Pre-operative radiotherapy may pose a significant risk for free-flap failure in oncologic patients undergoing scalp reconstruction following mesh cranioplasty. Awareness of associated risk factors ensures better pre-operative counseling and success of these reconstructive modalities and timing of pre-adjuvant treatment.
Objective: To comprehensively assess the level of achievement and demographics of national surgical society presidents. Background: Data on the accomplishments needed to rise to positions of national surgical leadership is scarce and merit alone does not always yield such opportunities. Recognizing the shortcomings of sex and ethnic diversity within academic surgical leadership, the American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and the Society of Black Academic Surgeons (SBAS) partnered to address these challenges by performing a comprehensive assessment of their presidents over the last 16 years. Methods: ACS, ASA, AWS, and SBAS presidents’ CVs, at the time of their presidential term, were assessed for demographics and scholastic achievements. Regression analyses controlling for age were performed to determine relative differences across societies. Results: A total of 62 of the 64 presidents’ CVs were received and assessed (97% response rate). There was a large discrepancy in the average age in years of ACS (70) and ASA (66) presidents compared to the AWS (51) and SBAS (53) presidents. For the ACS and ASA cohort, 87% were male and 83% were White, collectively. After controlling for age (52), the AWS and SBAS presidents’ scholastic achievements were comparable to the ACS (and ASA) cohort in 9 and 12 of the 15 accessed metrics, respectively. Conclusion: The ACS and ASA presidents’ CVs displayed unsurpassed scholastic achievement, and although not equivalent, both the AWS and the SBAS presidents had comparable attainment. These findings further substantiate that women and ethnic minority surgeons are deserving of additional national leadership consideration as organized medicine pursues a more diverse and reflective physician workforce.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs) isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full-dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post-therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.
Background Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 hours. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC.
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