Epigenetic therapy inhibits metastases by disrupting premetastatic niches.

Cancer recurrence after surgery remains an unresolved clinical problem1-3. Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4-6. There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7. Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy.

Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Is Female Representation Increasing in Society and Journal Editorial Boards in Oral and Maxillofacial Surgery?

PURPOSE: Surgical specialties, including oral and maxillofacial surgery (OMS), are traditionally male-dominated fields. This study aimed to analyze the proportions of female surgeons on specialty society boards and journal editorial boards in OMS in the United States and to assess whether they were proportionate with female representation in OMS academic faculty between 2011 and 2020. METHODS: A retrospective cohort study was performed using information obtained from the websites of two major OMS journals and information obtained directly from six American specialty societies for OMS. The predictor variable was time. The outcome variable was gender. Temporal changes in the proportion of women on society and journal editorial boards were compared with those amongst full-time board-certified faculty. Chi-squared test and simple linear regression were used for statistical analyses. RESULTS: Between 2011 and 2020, the proportion of women on editorial and society boards was 6.7% (31 women among 463 editorial board members) and 7.8% (43 women among 553 society board members), respectively. The proportion of women on editorial boards increased from 4.5% in 2011 to 10.6% in 2020 (ß = 0.656 [95% confidence interval, 0.336-0.975], P = .001) and that of women on society boards increased from 4.3% in 2011 to 10.3% in 2020 (ß = 0.645 [95% confidence interval, 0.252-1.037], P = .005). The proportion of women on editorial boards in 2011-2012 was significantly lower than that in full-time board-certified faculty positions (4.3% vs 11.0%, P = .045), whereas by 2019-2020, there was no difference between the 2 groups (9.8% vs 12.5%, P = .454). Similarly, the proportion of women on society boards in 2011-2012 tended to be lower than that in full-time board-certified faculty positions (5.6% vs 11.0%, P = .111), while in 2019-2020, no difference was observed between the 2 groups (10.4% vs 12.5%, P = .531). CONCLUSION: The proportion of women on society and journal editorial boards in OMS remains low but has progressively increased from 2011 to 2020, resulting in proportionate female representation in these positions compared with the gender composition of academic faculty in recent years. The current upward trend of female representation in leadership positions will hopefully present more diverse opportunities and mentorship/role models for trainees.

Disparities in Timing of Alveolar Bone Grafting and Dental Reconstruction in Patients With Clefts.

This study sought to identify disparities in the timing of alveolar bone grafting (ABG) surgery and the replacement strategy for missing maxillary lateral incisors for patients with clefts.A retrospective record review identified patients who underwent ABG. Multivariable regression analyzed the independent contribution of each variable.This institutional study was performed at the University of California, San Francisco.Patients who presented under age 12 and underwent secondary ABG between 2012 and 2020 (n = 160).The age at secondary ABG and the recommended dental replacement treatment for each patient, either dental implantation or canine substitution.The average age at ABG was 10.8 ± 2.1 years, 106 (66.3%) patients were not White, and 80 (50.0%) had private insurance. Independent predictors of older age at ABG included an income below $ 50 000 as estimated from ZIP code (ß = 15.0 months, 95% CI, 5.7-24.3, P = .002) and identifying as a race other than White (ß = 10.1 months, 95% CI, 2.1-18.0, P = .01). After ABG, patients were more likely to undergo dental implantation over canine substitution if they were female (odds ratio [OR] = 4.3, 95% CI, 1.3-17.1, P = .02) or had private insurance (OR = 12.5, 95% CI, 2.2-143.2, P = .01).Patients who were low-income or not White experienced delays in ABG, whereas dental implantation was more likely to be recommended for patients with private insurance. Understanding the sources of disparities in dental reconstruction of cleft deformities may reveal opportunities to improve equity.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Racial and Socioeconomic Disparities in Prompt Craniosynostosis Workup and Treatment.

The purpose of this study was to identify racial and socioeconomic disparities in craniosynostosis evaluation and treatment, from referral to surgery. Patients diagnosed with craniosynostosis between 2012 and 2020 at a single center were identified. Chart review was used to collect demographic variables, age at referral to craniofacial care, age at diagnosis, age at surgery, and surgical technique (open versus limited incision). Multivariable linear and logistic regression models with lasso regularization assessed the independent effect of each variable. A total of 298 patients were included. Medicaid insurance was independently associated with a delay in referral of 83 days [95% confidence interval (CI) 4-161, P=0.04]. After referral, patients were diagnosed a median of 21 days later (interquartile range 7-40), though this was significantly prolonged in patients who were not White (ß 23 d, 95% CI 9-38, P=0.002), had coronal synostosis (ß 24 d, 95% CI 2-46, P=0.03), and had multiple suture synostosis (ß 47 d, 95% CI 27-67, P<0.001). Medicaid insurance was also independently associated with diagnosis over 3 months of age (risk ratio 1.3, 95% CI 1.1-1.4, P=0.002) and undergoing surgery over 1 year of age (risk ratio 3.9, 95% CI 1.1-9.4, P=0.04). In conclusion, Medicaid insurance was associated with a 3-month delay in referral to craniofacial specialists and increased risk of diagnosis over 3 months of age, limiting surgical treatment options in this group. Patients with Medicaid also faced a 4-fold greater risk of delayed surgery, which could result in neurodevelopmental sequelae.

Neoadjuvant PD-1 Blockade in Resectable Lung Cancer.

BACKGROUND: Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. METHODS: In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses. RESULTS: Neoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab. CONCLUSIONS: Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute-Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621 .).

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Aquatic Activity-Related Craniofacial Injuries Presenting to United States Emergency Departments, 2010 to 2019.

PURPOSE: Aquatic activities are some of the most widely enjoyed sports and recreational activities in the United States. This study aimed to analyze the risks and types of craniofacial injuries associated with various aquatic activities. METHODS: We retrospectively analyzed aquatic activity-related craniofacial injuries between 2010 and 2019 using the National Electronic Injury Surveillance System database. Aquatic activities included swimming, diving, surfing, water skiing, and water tubing. Risks and types of craniofacial injuries were analyzed according to the types of aquatic activities, age, and sex. RESULTS: Among 48,112 patients with aquatic activity-related injuries, 9,529 (19.8%) had craniofacial injuries. In decreasing order of frequency, the causes of craniofacial injuries were swimming (79.6%), diving (7.5%), surfing (5.9%), water skiing (3.6%), and water tubing (3.5%). The proportion of craniofacial injuries among all injuries was higher in males than in females (22.8 vs 16.3%, P < .001), and decreased with age: 27.7% in 0 to 5 years, 21.5% in 6 to 11 years, 20.5% in 12 to 17 years, and 15.2% in ≥18 years (P < .001). Additionally, the proportion of craniofacial injuries was highest in diving (38.7%), and lowest in swimming (18.1%, P < .001). The male-to-female ratio in the proportion of patients with craniofacial injuries was highest in swimming at 1.42, and close to unity (0.97-1.13) in other activities. The most common type of craniofacial injury was laceration (43.5%), followed by concussion/internal organ injury (38.9%), contusion/abrasion (11.3%), and fracture (3%). Among all craniofacial injuries, the proportion of craniofacial fractures was highest in water tubing (8.5%) and lowest in swimming (2.2%, P < .001). CONCLUSIONS: Craniofacial injuries are a frequent cause of morbidity related to aquatic activities. Substantial variability exists in the risk and pattern of craniofacial injuries depending on the type of activity, age, and sex. These findings may aid in instituting educational programs and preventive measures against aquatic activity-related craniofacial injuries.

Current Status of Instagram Utilization by Oral and Maxillofacial Surgery Residency Programs: A Comparison With Related Dental and Surgical Specialties.

PURPOSE: The utility of social media in oral and maxillofacial surgery (OMS) residency programs has never been investigated, despite the increasing popularity of such platforms in academic medicine. As a specialty that strives for constant innovation, it is important for OMS programs to participate in the emerging concept of incorporating social media into medical and surgical education. Therefore, this study aimed to evaluate the use of Instagram in OMS residency programs in the United States. METHODS: A cross-sectional study of Instagram search data was performed. The Instagram accounts of OMS residency programs were searched, and their metrics were retrieved from June 1 to June 5, 2020. Factors correlated with the total number of followers were identified. The use of Instagram in OMS residency programs was compared with that in other related dental and surgical residency programs. RESULTS: Only 17 (18.7%) of 91 OMS residency programs had an Instagram account. The number of programs with Instagram accounts exhibited linear growth (R2 = 0.98) since December 2018. The median number of followers was 326 (range, 94 to 2,152), and the median number of posts was 9 (range, 2 to 40). The number of Instagram followers was positively correlated with the number of accounts followed, the number of total posts, and the number of educational posts, and it was negatively correlated with the Instagram engagement rate. Instagram presence did not differ among residency programs for orthodontics (18.2%), periodontics (5.5%), and OMS (P = .067). However, Instagram presence in OMS residency programs was significantly lower than that in plastic surgery (74.7%; P < .001) and otolaryngology residency programs (35.0%; P = .011). CONCLUSIONS: Instagram use in OMS residency programs is growing but is significantly lower than that in related surgical fields. This may represent a missed opportunity for promoting collaboration and efficiently delivering useful information to trainees.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

Isolated pulmonary recurrence after resection of pancreatic cancer: the effect of patient factors and treatment modalities on survival.

BACKGROUND: The literature suggests favorable survival for patients with isolated pulmonary recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) as compared to other recurrence patterns. Within this cohort, it remains unclear what factors are associated with improved survival. METHODS: Patients who developed pulmonary recurrence after pancreatectomy were selected from a prospective database. Predictors for post-recurrence survival (PRS) were analyzed using a multivariable Cox regression model. RESULTS: Ninety-six patients were included. Median recurrence-free survival (RFS), PRS and overall survival (OS) were 16.3, 18.8 and 39.6 months, respectively. Further systemic treatment and/or metastasectomy (n = 64, 67%) was associated with significantly improved PRS and OS when compared to best supportive care (n = 35, 22%) (26.3 vs. 5.3 and 48.1 vs. 18.4, respectively; both P < 0.001). Patients who were able to undergo metastasectomy (n = 19) achieved a PRS and OS of 35.0 and 68.9 months, respectively. More than 5 pulmonary lesions, symptoms and CA 19-9 ≥100 U/mL at time of recurrence were predictive of decreased PRS. A recurrence-free interval of >16 months and treatment for recurrence were independently associated with improved PRS. CONCLUSIONS: Isolated pulmonary recurrence occurs in 13% of patients with recurrent PDAC and is associated with a median OS of 40 months. Aggressive treatment in highly selected patients was correlated with improved survival.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

Reconstruction of ulnar defect with vascularized rib graft: A case report.

This case report describes the reconstruction of a segmental ulnar defect using a vascularized rib graft. A 27-year-old man was injured during military service by an improvised explosive device, resulting in bilateral through-the-knee amputations, left hand deformity, and a segmental left ulnar defect. After unsuccessful ulnar reconstruction with nonvascularized autologous bone and allograft bone substitutes, he presented to our institution. We removed the residual allograft fragments from the ulnar defect, harvested a vascularized left sixth rib with the intercostal artery and vein, secured the construct with internal hardware, and performed microanastomoses of the intercostal artery and vein to the posterior interosseous artery and vein. Postoperatively, he had a hematoma at the vascularized graft recipient site caused by anticoagulation therapy for his chronic deep vein thrombosis. Despite this, the rib graft successfully incorporated on the basis of radiographic and clinical examinations at 27 months. He had no pain and good function of the arm. The results of this case suggest that a vascularized rib graft for forearm reconstruction may be a viable option with minimal donor site morbidity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:160-164, 2017.