Contemporary Prophylactic Antibiotic Practices and Adjunct Therapies in Autologous Fat Grafting Procedures: A Survey of The Aesthetic Society Members.

Background: Autologous fat grafting (AFG) is a widely used surgical technique that involves extracting a patient's own adipose tissue and transferring it to different areas of the body. This practice is still evolving. Guidelines for antibiotic prophylaxis and use of adjuncts in plastic surgery are currently limited, with a notable absence of standardized guidelines for AFG. Objectives: In this survey, we assess contemporary antibiotic practices and adjuncts in AFG procedures. Methods: A 52-question survey was emailed to 3106 active members of The Aesthetic Society. Two hundred and ninety-three responses were recorded, representing a 9% response rate. Results: We analyzed 288 responses. The most common AFG procedures were facial (38%), gluteal (34%), and breast (27%) augmentation. Preoperative antibiotics were used by 84.0% overall, with rates of 74.3%, 88.0%, and 92.7% in face, breast, and gluteal AFG, respectively. Lipoaspirate-antibiotic mixing was reported by 19.8%, mainly during gluteal AFG (46.9%), and less so in face (2.8%) and breast (8%) AFG. Notably, 46.9% of surgeons administered prolonged prophylaxis for 72 h or more. Tranexamic acid was utilized by 39.9% of the surveyed surgeons. Platelet-rich plasma was used by 5.6%. Doppler ultrasound was incorporated by 16.7% in AFG, with 21.5% in gluteal AFG, 14% in the face, and 19% in breast procedures. Conclusions: In this survey, we offer insights into antibiotic practices and adjunct therapies in AFG, especially intraoperative antibiotic mixing. Practices among members of The Aesthetic Society vary from guidelines. It is crucial to standardize practices and conduct further research to pave the way for evidence-based guidelines in AFG.

Moral Distress, Organizational Climate, and the Risk of Burnout Among Physician Assistants in Oncology.

PURPOSE: Moral distress (MD) is the result of barriers or constraints that prevent providers from carrying out what they believe to be ethically appropriate care. This study was initiated to explore associations between MD, burnout, and the organizational climate (OC) for oncology physician assistants (PAs). METHODS: A national survey of oncology PAs was conducted to explore the associations between MD, OC, and burnout. The Nurse Practitioner-Primary Care OC Questionnaire was revised for oncology PAs to assess OC for PA practice. MD and burnout were assessed using the Measure of MD-Healthcare Professionals (MMD-HP) and the Maslach Burnout Inventory. RESULTS: One hundred forty-six oncology PAs are included in the analysis. PAs were mostly female (90%), White/Caucasian (84%), married/partnered (78%), and in medical oncology (73%), with mean age 41.0 years. The mean MMD-HP score for oncology PAs was 71.5 and there was no difference in MD scores on the basis of oncology subspecialty, practice setting, practice type, or hours worked per week. PAs currently considering leaving their position because of MD had significantly higher mean scores on the MMD-HP compared with those not considering leaving their position (108.2 v 64.8; P = .001). PAs with burnout also had significantly higher mean scores for MD compared with PAs without burnout (97.6 v 54.3; P < .001). A negative relationship between OC for PA practice and MD was only found for the PA-administration relations subscale, whereas all subscales were negatively associated with burnout. CONCLUSION: This study demonstrates that the risk of professional burnout increases significantly with increasing levels of MD. Additional research exploring the relationship between MD and burnout is needed.

Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

Association of Organizational Context, Collaborative Practice Models, and Burnout Among Physician Assistants in Oncology.

PURPOSE: Despite an increase in the number of physician assistants (PAs) in the oncology workforce, their potential to meet anticipated demand for oncology services may be hindered by high rates of burnout. The aim of this study was to examine the association between organizational context (OC) and burnout among oncology PAs to better understand factors associated with burnout. METHODS: A national survey of oncology PAs was conducted to explore relationships between burnout and the OC in which the PA practiced. The Areas of Worklife Survey (AWS) assessed OC by examining six key workplace qualities (workload, control, reward, community, fairness, and values). Burnout was assessed using the Maslach Burnout Inventory. RESULTS: PAs demonstrating burnout scored significantly lower across all domains of the AWS than those without burnout (P < .001 for each AWS subscale). The median score for each domain of the AWS and burnout (No v Yes) were as follows: workload (3.33 v 2.67), control (3.67 v 3.00), reward (4.00 v 3.67), community (4.00 v 3.67), fairness (3.33 v 2.67), and values (4.00 v 3.33). Multivariable analysis found that mismatches between the PA and their work environment in workload (odds ratio [OR] = 1.99; 95% CI, 1.32 to 3.02; P = .001), reward (OR = 1.89, 95% CI, 1.18 to 3.02; P = .008), and values (OR = 2.25; 95% CI, 1.31 to 3.88; P = .003) were more likely to report burnout. Differences in burnout in the context of workload were not explained by patient volume, practice structure, or professional autonomy. CONCLUSION: Workload, reward, and values were associated with greater odds of burnout, with workload being the most common mismatch in job fit. Sustainable workloads and consistency in rewards (financial, institutional, and social) for oncology PAs should be an employer's focus to help mitigate their risk of burnout.

Changes in Burnout Among Oncology Physician Assistants Between 2015 and 2019.

PURPOSE: Burnout has significant implications for the individual provider, the oncology workforce, and the quality of care for patients with cancer. The primary aim of this study was to explore temporal changes in burnout among physician assistants (PAs) in oncology in 2019 compared with 2015. METHODS: Oncology PAs were surveyed to assess for burnout using the Maslach Burnout Inventory according to the same cross-sectional design of the study performed in 2015. Comparison between oncology PAs in 2015 and 2019 in the prevalence of burnout and personal and professional characteristics was performed. RESULTS: Two hundred thirty-four participants completed the full-length survey. The participants in 2015 and 2019 were similar in age (41.8 v 40.3 years), sex (88.8% v 86.3% female), number of years as a PA in oncology (9.6 v 10), and percentage involved in academic practice (55.2% v 59.2%). There was a significant increase in burnout in 2019 compared with 2015 with 48.7% of PAs reporting at least one symptom of burnout compared with 34.8% (odds ratio for burnout, 2019 v 2015 = 1.92 [95% CI, 1.40 to 2.65], P < 0.001). The odds of burnout remained higher in 2019 compared with 2015 when adjusted for age, sex, relationship status, practice setting, subspecialty, practice type, and hours worked. Factors associated with burnout in both 2015 and 2019 include the percentage of time spent on patient care, collaborative physician relationship, number of hours worked, and satisfaction with compensation. No new factors associated with burnout emerged in 2019 that were not identified in 2015. CONCLUSION: The rate of burnout of oncology PAs has significantly increased. Burnout in oncology PAs is multifactorial, and the increase cannot be easily explained. Additional research is needed to better define the drivers of PA burnout.

Breast Reconstruction in Inflammatory Breast Cancer: An Analysis of Predictors, Trends, and Survival from the National Cancer Database.

INTRODUCTION: Survival for women diagnosed with inflammatory breast cancer (IBC) has improved with advances in multimodal therapy. This study was performed to evaluate trends, predictors, and survival for reconstruction in IBC patients in the United States. METHODS: Women who underwent mastectomy with or without reconstruction for IBC between 2004 and 2016 were included from the National Cancer Database. Predictors for undergoing reconstruction and association with overall survival were determined. RESULTS: Of 12,544 patients with IBC who underwent mastectomy, 1307 underwent reconstruction. Predictors of reconstruction included younger age, private insurance, higher income, performance of contralateral prophylactic mastectomy, and location within a metropolitan area (P < 0.001). The proportion of women having reconstruction for IBC increased from 7.3% to 12.3% from 2004 to 2016. Median unadjusted overall survival was higher in the reconstructive group l [93.7 months, 95% confidence interval (CI) 75.2-117.5] than the nonreconstructive group (68.1 months, 95% CI 65.5-71.7, hazard ratio = 0.79 95% CI 0.72-0.88, P < 0.001). With adjustment for covariates, differences in overall mortality were not significant, with hazard ratio of 0.95 (95% CI 0.85-1.06, P = 0.37). CONCLUSIONS: Reconstruction rates for IBC are increasing. Women with IBC who undergo reconstruction tend to be younger and are not at the increased risk of all-cause mortality compared to those not having reconstruction. The National Cancer Database does not differentiate immediate from delayed reconstruction. However, the outcomes of immediate reconstruction in carefully selected patients with IBC should be further studied to evaluate its safety. This could impact current guidelines, which are based largely on an expert opinion.

Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma.

Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on myeloid cells (TREMs) have emerged as potent modulators of the innate immune response. While various TREMs amplify inflammation, others dampen it and are emerging as important players in modulating tumor progression-for instance, soluble TREM-1 (sTREM-1), which is detected during inflammation, associates with disease progression, while TREM-2 expression is associated with tumor-promoting macrophages. We hypothesized that TREM-1 and TREM-2 might be co-expressed on tumor-infiltrating myeloid cells and that elevated sTREM-1 associates with disease outcomes, thus representing a possibility for mutual modulation in cancer. Using the 4T1 breast cancer model, we found TREM-1 and TREM-2 expression on MDSC and TAM and that sTREM-1 was elevated in tumor-bearing mice in multiple models and correlated with tumor volume. While TREM-1 engagement enhanced TNF, a TREM-2 ligand was detected on MDSC and TAM, suggesting that both TREM could be functional in the tumor setting. Similarly, we detected TREM-1 and Trem2 expression in myeloid cells in the RENCA model of renal cell carcinoma (RCC). We confirmed these findings in human disease by demonstrating the expression of TREM-1 on tumor-infiltrating myeloid cells from patients with RCC and finding that sTREM-1 was increased in patients with RCC. Finally, The Cancer Genome Atlas analysis shows that TREM1 expression in tumors correlates with poor outcomes in RCC. Taken together, our data suggest that manipulation of the TREM-1/TREM-2 balance in tumors may be a novel means to modulate tumor-infiltrating myeloid cell phenotype and function.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Overall tumor genomic instability: an important predictor of recurrence-free survival in patients with localized clear cell renal cell carcinoma.

Measurement of a tumor's overall genomic instability has gathered recent interest over the identification of specific genomic imbalances, as it may provide a more robust measure of tumor aggressiveness. Here we demonstrate the association of tumor genomic instability in the prediction of disease recurrence in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Genomic copy number analysis was performed using SNP-based microarrays on tumors from 103 ccRCC patients. The number of copy number alterations (CNAs) for each tumor was calculated, and a genomic imbalance threshold (GIT) associated with high stage and high-grade disease was determined. Cox proportional hazards regression analyzes were performed to assess the effect of GIT on recurrence-free survival adjusting for known confounders. In the cohort, copy number losses in chromosome arms 3p, 14q, 6q, 9p, and 1p and gains of 5q and 7p/q were common. CNA burden significantly increased with increasing stage (p < .001) and grade (p < .001). The median CNA burden associated with patients presenting with advanced stage (IV) and high-grade (III/IV) tumors was ≥9, defining the GIT. On regression analysis, GIT was a superior predictor of recurrence (Hazard Ratio 4.44 [CI 1.36-14.48], p = .01) independent of stage, with similar results adjusting for grade. These findings were confirmed using an alternative measure of genomic instability, weighted Genomic Integrity Index. Our data support a key role for genomic instability in ccRCC progression. More importantly, we have identified a GIT (≥ 9 CNAs) that is a superior and independent predictor of disease recurrence in high-risk ccRCC patients.

Breakfast in the Classroom Initiative and Students' Breakfast Consumption Behaviors: A Group Randomized Trial.

Objectives. To identify the effect of a Breakfast in the Classroom (BIC) initiative on the foods and drinks students consume in the morning.Methods. Sixteen public schools in Philadelphia, Pennsylvania, that provide universal breakfast participated in a group randomized trial to examine the effects of BIC with complementary nutrition promotion between 2013 and 2016. Control schools (n = 8) offered breakfast in the cafeteria before school. Baseline data were collected from 1362 students in grades 4 to 6. Endpoint data were collected after 2.5 years. Students self-reported the foods and drinks they consumed in the morning.Results. At endpoint, there was no effect of the intervention on breakfast skipping. Nearly 30% of intervention students consumed breakfast foods or drinks from multiple locations, as compared with 21% of control students. A greater proportion of intervention students than control students consumed 100% juice, and a smaller proportion consumed sugar-sweetened beverages and foods high in saturated fat and added sugar.Conclusions. A BIC initiative led to improvements in the types of foods and drinks students consumed in the morning. However, the program did not reduce breakfast skipping and increased the number of locations where students ate.

Effect of a Breakfast in the Classroom Initiative on Obesity in Urban School-aged Children: A Cluster Randomized Clinical Trial.

Importance: Serving breakfast in the classroom is promoted to increase participation in the federal School Breakfast Program. However, little is known about the effect of breakfast in the classroom on children's weight status. Objective: To evaluate the effect of a breakfast in the classroom initiative, which combined breakfast in the classroom with breakfast-specific nutrition education, on overweight and obesity among urban children in low-income communities. Design, Setting, and Participants: A cluster-randomized clinical trial among 1362 fourth- through sixth-grade students from low-income urban communities across 2.5 years. Sixteen kindergarten through eighth grade Philadelphia public schools with universal breakfast participated. Participants were recruited in September 2013, and the intervention began in January 2014. Data analysis took place from April 1, 2018, to August 30, 2018. Interventions: Intervention schools received a program that included breakfast in the classroom and breakfast-specific nutrition education. Control schools continued breakfast before school in the cafeteria and standard nutrition education. Main Outcomes and Measures: The primary outcome was the combined incidence of overweight and obesity. Secondary outcomes included the combined prevalence of overweight and obesity, incidence and prevalence of obesity, changes in body mass index (BMI) z score, and School Breakfast Program participation. Results: Among the 1362 students, mean (SD) age was 10.8 (0.96) years and 700 (51.4%) were female; 907 (66.6%) were black, 233 (17.1%) were Hispanic, 100 (7.3%) were white, 83 (6.1%) were Asian, and 39 were of multiple or other race/ethnicity. After 2.5 years, students in intervention schools had participated in the School Breakfast Program 53.8% of days, compared with 24.9% of days among students in control schools (ß = 0.33; 95% CI, 0.22-0.42). There was no difference between intervention and control schools in the combined incidence of overweight and obesity after 2.5 years (11.7% vs 9.3%; odds ratio [OR] 1.31; 95% CI, 0.85-2.02; P = .22). However, the incidence (11.6% vs 4.4%; OR, 2.43; 95% CI, 1.47-4.00) and prevalence (28.0% vs 21.2%; OR, 1.46; 95% CI, 1.11-1.92) of obesity were higher in intervention schools than in control schools after 2.5 years. Conclusions and Relevance: A breakfast in the classroom initiative increased participation in the School Breakfast Program and did not affect the combined incidence of overweight and obesity. However, the initiative had an unintended consequence of increasing incident and prevalent obesity. Further research is needed to identify approaches to increase participation in the School Breakfast Program that do not increase obesity among students. Trial Registration: ClinicalTrials.gov identifier: NCT01924130.

Title: efficacy of a food parenting intervention for mothers with low income to reduce preschooler's solid fat and added sugar intakes: a randomized controlled trial.

BACKGROUND: Few interventions have shown efficacy to influence key energy balance behaviors during the preschool years. OBJECTIVE: A randomized controlled trial (RCT) was used to evaluate the efficacy of Food, Fun, and Families (FFF), a 12 week authoritative food parenting intervention for mothers with low-income levels, to reduce preschool-aged children's intake of calories from solid fat and added sugar (SoFAS). METHODS: Mothers were randomly assigned to receive FFF (n = 59) or to a delayed treatment control (n = 60). The primary outcome was children's daily energy intake from SoFAS at the end of the 12 week intervention, controlling for baseline levels, assessed by 24-h dietary recalls. Secondary outcomes included children's daily energy intake, children's BMI z-scores, and meal observations of maternal food parenting practices targeted in FFF (e.g. providing guided choices). RESULTS: Participating mothers were predominantly African American (91%), with 39% educated beyond high school and 66% unemployed. Baseline demographics and child SoFAS intakes did not differ by group. Lost to follow-up was 13% and did not differ between groups. At post-intervention, FFF children consumed ~ 94 kcal or 23% less daily energy from SoFAS than children in the control group, adjusting for baseline levels (307.8 (95%CI = 274.1, 341.5) kcal vs. 401.9 (95%CI = 369.8, 433.9) kcal, FFF vs. control; p < 0.001). FFF mothers also displayed a greater number of authoritative parenting practices when observed post-intervention with their child at a buffet-style meal (Wilcoxon z = - 2.54, p = 0.012). Neither child total daily energy intake nor BMI z-scores differed between groups post-intervention. CONCLUSIONS: Findings demonstrate the initial efficacy of an authoritative food parenting intervention for families with low-income to reduce SoFAS intake in early childhood. Additional research is needed to evaluate longer-term effects on diet and growth. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov : #NCT03646201.

Predictive Value of Leukocyte- and Platelet-Derived Ratios in Rectal Adenocarcinoma.

BACKGROUND: Advances in treatment of rectal cancer have improved survival, but there is variability in response to therapy. Recent data suggest the utility of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in predicting survival. Our aim was to examine these ratios in rectal cancer patients and determine whether any association exists with overall survival (OS). METHODS: Using prospectively maintained institutional data, a query was completed for clinical stage II-III rectal adenocarcinoma patients treated from 2002 to 2016. We included patients who had a complete blood count collected before neoadjuvant chemoradiation (pre-CRT) and again before surgery (post-CRT). The LMR, NLR, and PLR were calculated for the pre-CRT and post-CRT time points. Potential cutpoints associated with OS differences were determined using maximally selected rank statistics. Survival curves were compared using log-rank tests and were adjusted for age and stage using Cox regression. RESULTS: A total of 146 patients were included. Cutpoints were significantly associated with OS for pre-CRT ratios but not for post-CRT ratios. Within the pretreatment group, a "low" (<2.86) LMR was associated with decreased OS (log-rank P = 0.004). In the same group, a "high" (>4.47) NLR and "high" PLR (>203.6) were associated with decreased OS (log-rank P < 0.001). With covariate adjustment for age, and separately for final pathologic stage, the associations between OS and LMR, NLR, and PLR each retained statistical significance. CONCLUSIONS: If obtained before the start of neoadjuvant chemoradiation, LMR, NLR, and PLR values are accurate predictors of 5-y OS in patients with locally advanced rectal adenocarcinoma.

The Utility of Preoperative Vascular Grading in Patients Undergoing Surgery First for Pancreatic Cancer: Does Radiologic Arterial or Venous Involvement Predict Pathologic Margin Status?

Controversy exists on accurately grading vascular involvement on preoperative imaging for pancreatic ductal adenocarcinoma. We reviewed the association between preoperative imaging and margin status in 137 patients. Radiologists graded venous involvement based on the Ishikawa classification system and arterial involvement based on preoperative imaging. For patients with both classifications recorded, we categorized vascular involvement as "None," "Arterial only," "Venous only," or "Both" and examined the association of vascular involvement and pathologic margin status. Of 134 patients with Ishikawa classifications, 63%, 17%, 11%, and 9% were graded as I, II, III, and IV, respectively. Of 96 patients with arterial staging, 74%, 16%, and 10% were categorized as stages i, ii, and iii, respectively. Of 93 patients with both stagings, 61% had no vascular involvement, 7% had arterial only, 14% had venous only, and 17% had both involved. Ishikawa classification was strongly associated with a positive SMA and SMV margin (p<0.001). However, for arterial staging, there was no association with SMA or SMV margin. Overall, Ishikawa grading was more predicative of arterial involvement and remained significant on multivariate analysis. The use of diagnostic imaging in predicting positive margins is more accurate when using a venous grading system.

Pathologic response following treatment for locally advanced rectal cancer: Does location matter?

BACKGROUND: Despite advances in the treatment of rectal adenocarcinoma, the management of locally advanced disease remains a challenge. The standard of care for patients with stages II and III rectal cancer includes neoadjuvant chemoradiation followed by total mesorectal excision and postoperative chemotherapy. Much effort has been dedicated to the identification of predictive factors associated with pathologic complete response (pCR). The aim of our study was to examine our institutional experience and determine whether any association exists between anatomic tumor location and the rate of pCR. We hypothesized that lesions more than 6 cm from the anal verge are more likely to achieve a pCR. METHODS: Using data from our prospectively maintained tumor registry, a query was completed to identify all patients with locally advanced rectal adenocarcinoma who underwent treatment at Fox Chase Cancer Center from 2002 to 2015. Demographics, pretreatment, posttreatment, and final pathologic TNM staging data were collected as well as treatment intervals in days, recurrence status, overall survival, and disease-free survival. Patients with incomplete endoscopic data, staging information, survival, or recurrence status were excluded. The primary outcome measured was the degree of pathologic response. Logistic regression was used to adjust for covariates. RESULTS: Of the 135 patients eligible in the study cohort, 39% were female and 61% were male. Regarding initial clinical stage, 43% were stage II and 57% were stage III. A total of 29% had a pCR, 43% had partial pathologic response, and 28% had no response to neoadjuvant treatment. Tumor location ranged from 0 to 13 cm from the anal verge. Longitudinal tumor length was recorded in 111 patients, facilitating the calculation of mean tumor distance from the anal verge. This ranged from 0 to 15.5 cm. Univariate and multivariable analyses were completed using pCR as a primary outcome. No statistically significant difference was noted based on tumor location, regardless of measurement approach. CONCLUSIONS: Anatomic location of cancer of the rectum does not affect pCR after neoadjuvant therapy and subsequent surgical resection.

Benefits of Supplemental Jejunostomy Tube Feeding During Neoadjuvant Therapy in Patients with Locally Advanced, Potentially Resectable Esophageal Cancer.

BACKGROUND: Standard treatment for locally advanced esophageal cancer includes neoadjuvant therapy followed by surgical resection. However, many patients experience a period of decreased oral intake during neoadjuvant treatment and are at risk for malnutrition. We hypothesize that use of jejunostomy tube (j-tube) feedings during neoadjuvant therapy in selected patients may be associated with better perioperative outcomes. METHODS: A prospectively collected database at a single institution was retrospectively analyzed. The study period was from 2005 to 2015. Patients who underwent j-tube placement before neoadjuvant therapy before definitive resection for esophageal cancer were included in the analysis. Perioperative outcomes were compared between patients who adhered to recommended tube feeds during neoadjuvant therapy (users) and patients who did not adhere (nonusers). RESULTS: During the study period, 94/301 patients received a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds regularly during the neoadjuvant phase, while 21 patients did not. The groups did not differ significantly with respect to clinical factors such as dysphagia on presentation, postneoadjuvant therapy performance status, or Charlson Comorbidity Index. Perioperative pneumonia rates were lower in j-tube users compared to nonusers (6.8% [5 of 73] versus 23.8% [5 of 21]), respectively, P = .036); this difference remained significant with adjustment for type of surgery (odds ratio = 0.16, P = .018). CONCLUSIONS: j-Tube users had a significantly lower incidence of pneumonia within 30 days of curative resection when compared to nonusers. j-Tube feedings during neoadjuvant therapy for selected patients with locally advanced esophageal cancer should be encouraged.

LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis.

BACKGROUND: Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of lncRNAs has been observed in breast cancer development, their roles in breast cancer progression and metastasis are still poorly understood. METHODS: To identify novel breast cancer-associated lncRNA candidates, we employed a high-density SNP array-based approach to uncover intergenic lncRNA genes that are aberrantly expressed in breast cancer. We first evaluated the potential value as a breast cancer prognostic biomarker for one breast cancer-associated lncRNA, LincIN, using a breast cancer cohort retrieved from The Cancer Genome Atlas (TCGA) Data Portal. Then we characterized the role of LincIN in breast cancer progression and metastasis by in vitro invasion assay and a mouse tail vein injection metastasis model. To study the action of LincIN, we identified LincIN-interacting protein partner(s) by RNA pull-down experiments followed with protein identification by mass spectrometry. RESULTS: High levels of LincIN expression are frequently observed in tumors compared to adjacent normal tissues, and are strongly associated with aggressive breast cancer. Importantly, analysis of TCGA data further suggest that high expression of LincIN is associated with poor overall survival in patients with breast cancer (P = 0.044 and P = 0.011 after adjustment for age). The functional experiments demonstrate that knockdown of LincIN inhibits tumor cell migration and invasion in vitro, which is supported by the results of transcriptome analysis in the LincIN-knockdown cells. Furthermore, knockdown of LincIN diminishes lung metastasis in a mouse tail vein injection model. We also identified a LincIN-binding protein, NF90, through which overexpression of LincIN may repress p21 protein expression by inhibiting its translation, and upregulation of p21 by LincIN knockdown may be associated with less aggressive metastasis phenotypes. CONCLUSIONS: Our studies provide clear evidence to support LincIN as a new regulator of tumor progression-metastasis at both transcriptional and translational levels and as a promising prognostic biomarker for breast cancer.

Mutational studies on single circulating tumor cells isolated from the blood of inflammatory breast cancer patients.

PURPOSE: The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly. METHODS: Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™. Samples with 20 or more CTCs were chosen to isolate single CTCs using the DEPArray™. RESULTS: Genomic alterations were studied in primary tumor or metastatic sites from 32 IBC patients. Genes with high-frequency mutations were as follows: TP53 (69%), RB1 (16%), PIK3CA (13%), and also ErbB2 (3%). At least once during treatment, CTCs were detected in 26 patients with metastatic IBC, in two patients with locally advanced IBC, and four patients had no detectable CTCs. Per 7.5 mL of blood, fifteen patients (47%) had ≥20 CTCs and six of them were chosen at random to isolate single CTCs. These cells were tested for the presence of TP53, RB1, PIK3CA, and/or ErbB2 mutations previously found in matching tissue biopsies. The isolated CTCs showed the same mutations as primary or metastatic tumor samples. Intra-patient CTC heterogeneity was found by the presence of different CTC subclones, with some CTCs harboring different combinations of mutated and wild-type genes. CONCLUSIONS: Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers as the disease progresses and identify potential therapeutic targets in IBC patients.

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

INTRODUCTION: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era. MATERIALS AND METHODS: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates. RESULTS: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates. CONCLUSION: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.

Young Age Increases Risk of Lymph Node Positivity in Early-Stage Rectal Cancer.

BACKGROUND: The risk of lymph node positivity (LN+) in rectal cancer is a parameter that impacts therapeutic recommendations. We aimed to quantify the effect of younger age on LN+ in rectal cancer. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, patients with rectal cancer diagnosed between 1988 and 2008 were identified. Patients were stage I-III, without preoperative radiotherapy, at least one lymph node examined, and a standard rectal cancer operation performed. The association of age and LN+ status was examined with logistic regression separately for each T stage, adjusting for multiple covariates. Poisson regression was used to evaluate age and number of positive lymph nodes (LNs). All statistical tests were two-sided. RESULTS: Fifty-six thousand seventy-six patients were identified, including 1194 (2.1%) patients age 20 to 39 years at diagnosis and 4199 (7.5%) patients age 40 to 49 years (defined as young). For each T stage, LN+ was inversely associated with age (all P < .001). For T1, T2, and T3, age remained predictive of LN+ status after adjustment for number of LNs examined and other covariates (P < .001 for each stage). Adjusted odds ratios (ORs) for LN+ for age 20 to 39 vs 60 to 69 were: T1: 1.97(95% confidence interval [CI] = 1.36 to 2.86); T2: 1.48 (95% CI = 1.13 to 1.95); T3: 1.30 (95% CI = 1.10 to 1.53). Young age was a statistically significant predictor of an increased number of LNs positive for stage T2 (P = .042) and T3 (P = .002). CONCLUSION: In this large national dataset, young age at diagnosis is associated with an increased risk of LN+. This finding merits further investigation and may ultimately impact treatment decision-making for young early-stage patients.