Value of an interactive phone application in an established enhanced recovery program.

PURPOSE: An interactive mobile phone application was added to an established Enhanced Recovery After Surgery (ERAS) program to determine the impact on ERAS compliance as well as clinical outcomes. METHODS: We identified patients undergoing elective colorectal surgery enrolled in our ERAS program from February 2017 to July 2018. Patients enrolled in a phone application were compared with those not enrolled in terms of age, sex, diagnosis, operative approach, bowel preparation, oral intake and solid food intake, ERAS pathway adherence, and clinical outcomes. RESULTS: A total of 289 patients were included: 147 enrolled and 142 not enrolled in the phone application. The mean age of enrollees was 53.0 years, compared with 58.3 years for the non-enrollees (p = 0.003). The mean ERAS pathway medication adherence for enrollees was 82.1% versus 76.8% for those not enrolled (p = 0.005). The mean LOS and SSI rates for those enrolled versus not enrolled in the phone application was 4.4 days versus 6.4 days (p = 0.006) and 3.4% versus 11.3% (p = 0.019), respectively. There was no significant difference in readmission rates between enrollees and non-enrollees (15% versus 10.6%, p = 0.345). The mean total cost of patients enrolled was $11,560; total cost of those not enrolled was $13,946 (p = 0.024). CONCLUSIONS: Use of an interactive phone application is associated with improved medication ERAS adherence along with significant reduction in length of stay and SSI rates without increasing total cost.

Enabling chiral separations in discovery chemistry with open-access chiral supercritical fluid chromatography.

Work from this paper details a novel walk-up open-access (OA) approach to enable chiral analytical method development and preparative separation of enantiomers in early discovery chemistry using supercritical fluid chromatography (SFC). We have demonstrated the success of this OA approach using immobilized chiral stationary phases (CSPs). After screening a diverse set of racemic drug candidates, we have concluded that a simplified OA chiral SFC platform can successfully purify approximately 60% of the analysed racemates. This streamlined OA workflow enables medicinal chemists with limited expertise in chiral method development to successfully and rapidly purify enantiomers for their projects using Waters UPC2 and Prep100-SFC instrumentation.

Acute cholecystitis: comparing clinical outcomes with TG13 severity and intended laparoscopic versus open cholecystectomy in difficult operative cases.

INTRODUCTION: The revised Tokyo Guidelines include criteria for determining the severity of acute cholecystitis with treatment algorithms based on severity. The aim of this study was to investigate the relationship of the revised Tokyo Guidelines severity grade to clinical outcomes of cholecystectomy for acute cholecystitis. METHODS: We identified 66 patients with acute cholecystitis from a prior study of difficult cholecystectomy cases. We examined the relationship between severity grade and multiple variables related to perioperative and postoperative outcomes. RESULTS: A more severe revised Tokyo Guidelines grade was associated with a higher number of complications (p = 0.03) and a higher severity of complications (p = 0.01). Severity grade did not predict operative time, estimated blood loss, intensive care unit admission or length of stay. Compared to planned open cholecystectomy, intended laparoscopic cholecystectomy was associated with significantly fewer total and Clavien-Dindo grade 3 complications, fewer intensive care unit admissions, and shorter length of stay (p values range from 0.03 to < 0.0001). CONCLUSION: In technically difficult operations for acute cholecystitis, the revised Tokyo guidelines severity grade correlates with the number and severity of complications. However, intended performance of laparoscopic cholecystectomy rather than open cholecystectomy in difficult operations predicts broader beneficial outcomes than severity grade.

Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment.

Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multicycle chemotherapies, resulting in short- and long-term toxicities. Here, we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment. The intratumoral drug concentration was significantly higher with intratumoral delivery versus IV. Furthermore, intratumor delivery decreased the maximum plasma concentration compared to IV delivery, reducing systemic exposure and possibly reduing long-term side effects of chemotherapy exposure. Histopathologically, tumors with remission periods >25 days before recurrence transformed from a "small-round-blue cell" (SBRC) to predominantly "large cell" neuroblastoma (LCN) histopathology, a more aggressive tumor subtype with unfavorable clinical outcomes. These results show that intratumoral chemotherapy delivery may be a treatment strategy for pediatric neuroblastoma, potentially translatable to other focal tumors types. Furthermore, this treatment modality allows for a clinically relevant mouse model of tumor transformation that may be used for studying the phenotypical tumor recurrence and developing more effective treatment strategies for recurrent tumors.

The effect of tobacco use on outcomes of laparoscopic and open inguinal hernia repairs: a review of the NSQIP dataset.

BACKGROUND: As the effort to reduce postoperative morbidity and mortality continues, the search for modifiable patient risk factors to reduce complications is ongoing. Tobacco use is associated with impaired wound healing, but its effect on inguinal hernia repair has not been studied in a large population. An ACS-NSQIP dataset was used to evaluate the effect of tobacco use on outcomes of inguinal hernia repairs. METHODS: The ACS-NSQIP dataset was queried for patients who underwent open or laparoscopic inguinal hernia repairs, by primary procedure CPT codes, between years 2009-2012. Tobacco use was registered, as defined by the ACS-NSQIP, in two ways: current smoking (within the past 12 months), or history of smoking (having ever smoked). Univariate and multivariate analyses were used to investigate outcome variables for 30-day morbidity by type of smoking status, while adjusting for preoperative risk factors. RESULTS: During the study period, 90,162 patients underwent inguinal hernia repair. 76 % of the cases were open compared to 24 % laparoscopic. The population was overwhelmingly male, 91 %, compared to 9 % female. The average age of patients was 42.5 years. Of the available data (69 % of patients), 38.5 % had a history of smoking. 18 % had smoked within the 12 months prior to surgery (current smokers). Their average number of pack years was 27.2 (SD 24.0) compared to 4.5 pack years (SD 14.7) for those who had not smoked 12 months prior to surgery (historical smokers). Using Fisher's exact test, having ever smoked was found to be significantly associated with pneumonia (p = 0.0008) and return to the operating room (p = 0.010). This relationship held when preoperative variables were controlled for using logistic regression (pneumonia, p = 0.002; return to the operating room, p = 0.002). When preoperative variables were controlled for and logistic regression was performed for current smokers, there was also a significant association with pneumonia (p = 0.005) and return to the operating room (p = 0.01). CONCLUSION: Current smoking status is a modifiable risk of patients undergoing laparoscopic and open inguinal hernia repair. Failure to quit smoking prior to surgical repair is associated with complications like pneumonia and return to the operating room.

The effect of tobacco use on outcomes of laparoscopic and open ventral hernia repairs: a review of the NSQIP dataset.

INTRODUCTION: Tobacco smoking is a known risk factor for complications after major surgical procedures. The full effect of tobacco use on these complications has not been studied over large populations for ventral hernia repairs. This effect is more important as the preoperative conditioning, and optimization of patients is adopted. We sought to use the prospectively collected ACS-NSQIP dataset to evaluate respiratory and infectious complications for patients undergoing both laparoscopic and open ventral hernia repairs. METHODS: The ACS-NSQIP dataset was queried for patients who underwent open or laparoscopic ventral hernia repairs, by primary procedure CPT codes, between years 2009-2012. Smoking use was registered as defined by the ACS-NSQIP, as both a current smoker (within the prior 12 months) or as a history of smoking (having ever smoked). Univariate and multivariate analyses were used to investigate postoperative complications for 30-day morbidity and mortality by smoking status while adjusting for preoperative risk factors. RESULTS: The majority of cases were open, 82 %, compared to laparoscopic 18 %. Sex was evenly distributed with 58 % female and 42 % male; however, there was a difference in the distribution of current smokers (p = 0.03). On analysis there were significantly more respiratory complications (p = 0.0003) and infectious complications (p < 0.0001). When controlling for sex, age, and type of surgery, using logistic regression, there were associations between smoking in the prior 12 months and respiratory complications, including pneumonia (p < 0.0001), and re-intubation (p < 0.0001). Similar associations were seen on logistic regression if a patient ever smoked; including pneumonia (p < 0.0001), re-intubation (p < 0.0001), and failure to wean (p < 0.0001). CONCLUSION: Smoking tobacco, both current and historical use, leads to an increase in both respiratory and infectious complications. As more centers try to preoperatively condition patients for elective hernia repairs, it is important to note that patients may never return to the baseline outcomes of patients who never smoked.

High-throughput digital quantification of Alzheimer disease pathology and associated infrastructure in large autopsy studies.

High-throughput digital pathology offers considerable advantages over traditional semiquantitative and manual methods of counting pathology. We used brain tissue from 5 clinical-pathologic cohort studies of aging; the Religious Orders Study, the Rush Memory and Aging Project, the Minority Aging Research Study, the African American Clinical Core, and the Latino Core to (1) develop a workflow management system for digital pathology processes, (2) optimize digital algorithms to quantify Alzheimer disease (AD) pathology, and (3) harmonize data statistically. Data from digital algorithms for the quantification of ß-amyloid (Aß, n = 413) whole slide images and tau-tangles (n = 639) were highly correlated with manual pathology data (r = 0.83 to 0.94). Measures were robust and reproducible across different magnifications and repeated scans. Digital measures for Aß and tau-tangles across multiple brain regions reproduced established patterns of correlations, even when samples were stratified by clinical diagnosis. Finally, we harmonized newly generated digital measures with historical measures across multiple large autopsy-based studies. We describe a multidisciplinary approach to develop a digital pathology pipeline that reproducibly identifies AD neuropathologies, Aß load, and tau-tangles. Digital pathology is a powerful tool that can overcome critical challenges associated with traditional microscopy methods.

Diversity-oriented synthesis encoded by deoxyoligonucleotides.

Diversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.

Integrated and automated high-throughput purification of libraries on microscale.

We herein report the development of an automation platform for rapid purification and quantification of chemical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on analytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.

Identification of a PCSK9-LDLR disruptor peptide with in vivo function.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employ an affinity-based screen of 1013in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to molecules with enhanced function and pharmacokinetic properties (e.g., 13PCSK9i). In mice, 13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner. 13PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.

Roux-en-Y gastric bypass decreases serum inflammatory markers and cardiovascular risk factors in obese diabetics.

BACKGROUND: Obesity and type 2 diabetes mellitus are associated with elevated levels of inflammatory markers. This chronic inflammation is known to contribute to increased risk of cardiovascular disease in these populations. Laparoscopic Roux-en-Y gastric bypass is associated with a high rate of diabetes remission. We hypothesize that laparoscopic Roux-en-Y gastric bypass decreases systemic inflammatory markers and cardiovascular disease risk factors in obese diabetics. METHODS: This was a single-institution prospective cohort study of 61 obese patients with type 2 diabetes mellitus. A total of 30 patients underwent laparoscopic Roux-en-Y gastric bypass surgery, and 31 patients underwent standard medical therapy with diabetes support and education. Collected data included preoperative and postoperative inflammatory biomarkers and clinical parameters. RESULTS: Twelve months after undergoing laparoscopic Roux-en-Y gastric bypass, controlling for sex and age, there was a significant correlation between a change in interleukin-6 and a change in systolic blood pressure (Spearman r = 0.41, P = .03). Similarly, when sex and age were controlled for in the laparoscopic Roux-en-Y gastric bypass group, a statistically significant relationship remained between percent excess weight loss and change in interleukin-6 (P = .001). CONCLUSION: A significant relationship exists between decreased systemic interleukin-6 levels and both excess weight loss and lowered systolic blood pressure after laparoscopic Roux-en-Y gastric bypass in obese patients with diabetes mellitus. These correlations may explain the decreased risk of cardiovascular disease after surgical weight reduction in this patient population.

Treating Positive Axillary Disease in Elderly Breast Cancer Patients: The Impact of Age on Radiation Therapy.

INTRODUCTION: Breast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment. METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy. RESULTS: Increasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment. CONCLUSION: Patient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.

Should Pre-Transplant Hemoglobin A1c Be Used to Predict Post-Transplant Compliance in End-Stage Renal Disease Patients Undergoing Kidney Transplantation?

BACKGROUND Patient compliance with immunosuppressive therapy after transplant has impacts on both graft and patient outcomes. For diabetic end-stage renal disease (ESRD) patients who are undergoing evaluation for kidney transplantation in our program, hemoglobin A1c (HbA1c) level of >10% is used as a flag that the patient may be at risk for noncompliance and that more comprehensive psychosocial screening is needed prior to transplant. We evaluated the association between pre-transplant HbA1c level and post-transplant compliance, as no study to date has looked at this in the transplant population. MATERIAL AND METHODS The charts of 392 patients who received a kidney transplant at a single institution between July 2008 and June 2012 were retrospectively reviewed. One hundred and sixty-five diabetic patients who received a kidney transplant alone were included in the final analysis. Our predictive variable was HbA1c level greater than 7.7% based on previous reports in the diabetic population. Outcome measures were graft survival, rejection episodes, unexplained low immunosuppressant levels, and documented noncompliance. RESULTS There were no statistically significant differences between the HbA1c groups of ≤7.7% and >7.7% in outcomes of failed grafts (22.0% and 17.8%, p=0.2), rejection episodes (15.0% and 6.7%, p=0.3), unexplained low immunosuppressant level (46.6% and 37.9%, p=0.3), and documented noncompliance (25.0% and 16.7%, p=0.4). CONCLUSIONS In diabetic ESRD patients selected for renal transplantation, elevated pre-transplant HbA1c levels, defined as HbA1c >7.7%, are not predictive of post-transplant medication compliance. We advocate that this group of patients should not be denied transplant solely on their elevated pre-transplant HbA1c.

Operative resection in early stage pancreatic neuroendocrine tumors in the United States: Are we over- or undertreating patients?

BACKGROUND: Many current guidelines recommend nonoperative management for pancreatic neuroendocrine tumors <2 cm. The objective of this study was to evaluate the utilization and outcomes of resection for these pancreatic neuroendocrine tumors in the United States. METHODS: Using the National Cancer Database (2004-2014), 3,243 cases of T1 (≤2.0 cm) pancreatic neuroendocrine tumors were identified. Additional patient and tumor characteristics were examined. Multivariate models were used to identify factors that predicted resection and to assess patient survival after resection. RESULTS: 75% of pancreatic neuroendocrine tumors measuring 0 to 1.0 cm and 80% of pancreatic neuroendocrine tumors measuring >1.0 and ≤2.0 cm were resected. Eighty-four pancreatic neuroendocrine tumors were functional, of which 82% were resected. Variables influencing resection included positive lymph nodes, tumor in body or tail of pancreas, well or moderately differentiated tumors, and resection at academic medical centers (odds ratio 1.5-4.9). When controlling for other variables, patients with pancreatic neuroendocrine tumors 1 to 2 cm who underwent resection had a prolonged 5-year survival rate (hazard ratio 0.51, confidence interval 0.34-0.75) when compared with those who did not undergo resection. This survival benefit of resection was not found for pancreatic neuroendocrine tumors 0 to 1 cm (hazard ratio = 0.63, confidence interval 0.36-1.11). CONCLUSIONS: Contrary to many current recommendations, most patients with pancreatic neuroendocrine tumors ≤2.0 cm undergo surgical resection in the United States. A survival benefit was found for resection of pancreatic neuroendocrine tumors 1 to 2 cm, suggesting that current recommendations should perhaps be revised.

Risk factors associated with positive resection margins in patients with adrenocortical carcinoma.

BACKGROUND: Positive resection margins are associated with worse survival after surgery for adrenocortical carcinoma (ACC). We aimed to identify risk factors for positive margins post-resection. METHODS: The NCDB was queried for ACC patients from 2006 to 2015. Patients with positive versus negative resection margins post-surgery were compared using Chi-square tests. Survival based on adjuvant treatment was assessed using Kaplan-Meier curves. RESULTS: 1,973 patients with ACC were identified, 217 (11.0%) with positive margins. Multivariable analysis identified extra-adrenal extension (HR 4.92, p < 0.001), lymph node metastases (HR 2.64, p = 0.001), and distant metastases (HR 1.53, p = 0.03) as risk factors for positive margins. No significant difference in margin status existed between patients who had an open versus minimally invasive procedure (p = 0.6). Positive margin patients receiving adjuvant radiation (p = 0.007) or combined chemo-radiation (p = 0.001) had the longest survival. CONCLUSION: No modifiable risk factors were identified, but patients with positive margins receiving adjuvant radiation or chemo-radiation had the longest survival.

Short-Term Outcomes of Conversion of Failed Gastric Banding to Laparoscopic Sleeve Gastrectomy or Roux-En-Y Gastric Bypass: a Meta-Analysis.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is associated with high long-term failure rates, often requiring conversion to an alternative bariatric procedure. The most efficacious procedure after failed LAGB is subject to debate. Our objective was to compare 12-month weight loss following laparoscopic sleeve gastrectomy (LSG) vs. laparoscopic Roux-en-Y gastric bypass (LRYGB) performed for insufficient weight loss or weight regain after LAGB. METHODS: A systematic search was conducted in PubMed and Medline for English language studies comparing weight loss after a conversion surgery for failed gastric banding. We examined studies with patients who had at least 1-year follow-up and included conversions to both LSG and LRYGB. A fixed effects model was created, and variance measures were calculated to measure heterogeneity. Both were analyzed for significance. All statistical analyses were conducted with the "meta" package in R 3.3.2. RESULTS: The initial search produced 17 studies. Six studies, consisting of 205 LSG and 232 LRYGB patients, met our inclusion criteria and were included in the review. Heterogeneity among studies was high (Q = 23.1; p < 0.001). There was no statistically significant difference in weight loss after 12 months between the groups (p = 0.14). CONCLUSIONS: It remains unknown which conversion procedure is more appropriate to perform after a failed gastric band in order to achieve the highest weight loss potential. In our meta-analysis, there was no difference in weight loss after 12 months in patients who were converted to LSG or LRYGB. Further studies and longer follow-up comparisons are required before firm conclusions can be drawn.

Obesity Does Not Influence Management of Advanced Breast Cancer in the Elderly.

BACKGROUND: Obesity is becoming increasingly common in the elderly population, and it adds to the complexity of treatment decisions in this population. We aimed to investigate whether body mass index (BMI) affects care in this subset of patients. PATIENTS AND METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital and compared BMI to treatment received, clinical stage, and hormone receptor status. RESULTS: Performance of radiation therapy, axillary surgery, and chemotherapy was compared in the elderly population over lower and higher BMI, and no significant difference was detected. Although there was a trend for increasing clinical stage to be associated with a lower BMI, this was not statistically significant (P = .06). CONCLUSION: Obesity does not appear to influence treatment decisions in patients over the age of 70 years. Breast cancer providers should turn to other patient and clinical factors when deciding treatment plans in this patient population. Further investigation is needed to examine how obesity influences tumor biology, diagnosis, and treatment decisions.

Laparoscopic Parenchymal-Sparing Hepatectomy: the New Maximally Minimal Invasive Surgery of the Liver-a Systematic Review and Meta-Analysis.

BACKGROUND: Parenchymal-sparing hepatectomies (PSH) are liver resections with preservation of as much liver parenchyma as possible. PSH can be performed laparoscopically (LPSH), but access to the posterosuperior segments is difficult and they are challenging when there are multiple bilobar lesions; the procedure may require repositioning and may be long and cumbersome. The objective of this systematic review is to analyze the feasibility and limitations of laparoscopic PSH in the literature. METHODS: A systematic review of the literature was performed by searching Medline/PubMed, Scopus, and Cochrane databases. Resections were categorized by segment(s), and data regarding operative time, blood loss, length of hospital stay, complications, and R0 resection were analyzed. RESULTS: Of 351 studies screened for relevance, 48 studies were reviewed. Ten publications fulfilled inclusion criteria, reporting data from 579 patients undergoing LPSH. The most common indication was CRLM (58%) followed by hepatocellular carcinoma (16%). Only 92 patients were reported to have resections of more than one tumor; the maximum number of lesions resected was seven. Of resected lesions, 21.5% were located in the cranial segments. Mean operating time was 335.2 min, estimated blood loss was 462 cc, and hospital stay was 7.6 days. Conversion rate was 9.7%, and complications occurred in 19.4% of cases. No perioperative mortality was reported. R0 resections were achieved in 87.7% of cases. CONCLUSION: Laparoscopic PSH is performed and reported, but the data quality is low so far. The main limitation of LPSH is the low number of lesions resected, especially for bilobar, metastatic disease. Prospective reports with tumor-specific oncological data are desirable.

Evolution of the Surgical Technique for "Breast in a Day" Direct-to-Implant Breast Reconstruction: Transitioning from Dual-Plane to Prepectoral Implant Placement.

BACKGROUND: Direct-to-implant breast reconstruction offers the intuitive advantages of shortening the reconstructive process and reducing costs. In the authors' practice, direct-to-implant breast reconstruction has evolved from dual-plane to prepectoral implant placement. The authors sought to understand postoperative complications and aesthetic outcomes and identify differences in the dual-plane and prepectoral direct-to-implant subcohorts. METHODS: A retrospective review of a prospectively maintained database was conducted from November of 2014 to March of 2018. Postoperative complication data, reoperation, and aesthetic outcomes were reviewed. Aesthetic outcomes were evaluated by a blinded panel of practitioners using standardized photographs. RESULTS: One hundred thirty-four direct-to-implant reconstructions were performed in 81 women: 42.5 percent were dual-plane (n = 57) and 57.5 percent were prepectoral (n = 77). Statistical analysis was limited to patients with at least 1 year of follow-up. Total complications were low overall (8 percent), although the incidence of prepectoral complications [n = 1 (2 percent)] was lower than the incidence of dual-plane complications [n = 7 (12 percent)], with the difference approaching statistical significance (p = 0.07). Panel evaluation for aesthetic outcomes favored prepectoral reconstruction. Pectoralis animation deformity was completely eliminated in the prepectoral cohort. CONCLUSIONS: The authors present the largest comparative direct-to-implant series using acellular dermal matrix to date. Transition to prepectoral direct-to-implant reconstruction has not resulted in increased complications, degradation of aesthetic results, or an increase in revision procedures. Prepectoral reconstruction is a viable reconstructive option with elimination of animation deformity and potential for enhanced aesthetic results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress?

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials. METHODS: The National Cancer Database was used to examine treatment patterns and survival in patients diagnosed with ACC from 2006 to 2015. Treatment modalities were compared within that group and with a historical cohort (1985 to 2005). χ2 tests were performed, and Cox proportional hazards models were created. RESULTS: From 2006 to 2015, 2752 patients were included; 38% of patients (1042) underwent surgery alone, and 31% (859) underwent surgery with adjuvant therapy. Overall 5-year survival rates for all stages after resection were 43% (median, 41 months) in the contemporary cohort and 39% (median, 32 months) in the historical cohort. After 2007, patients who underwent surgery were more likely to receive adjuvant chemotherapy (P = 0.005), and 5-year survival with adjuvant chemotherapy improved (41% vs 25%; P = 0.02). However, survival did not improve in patients with unresectable tumors after 2011 compared with 2006 to 2011 (P = 0.79). Older age, tumor size ≥10 cm, distant metastases, and positive margins were associated with lower survival after resection (hazard ratio range: 1.39 to 3.09; P < 0.03). CONCLUSIONS: Since 2007, adjuvant therapy has been used more frequently in patients with resected ACC, and survival for these patients has improved but remains low. More effective systemic therapies for patients with ACC, especially those in advanced stages, are desperately needed.