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Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled “Next Steps in Adolescent and Young Adult Oncology” summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. Cancer 2016;122:1017–1028. © 2016 American Cancer Society

BACKGROUNDAlthough colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown.METHODSThe current study was a population‐based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease‐specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis.RESULTSOf 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease‐specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease.CONCLUSIONSPatients with CRC diagnosed at age <50 years are more likely to present with advanced‐stage disease. However, they receive more aggressive therapy and achieve longer disease‐specific survival, despite the greater percentage of patients with advanced‐stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. Cancer 2016;122:929–34. © 2016 American Cancer Society.

PurposeTo evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness.Materials and MethodsProspectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t‐test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria.ResultsNineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001).ConclusionCP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81–88.

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null ( Lrrc10−/−) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10−/−mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10−/−mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10−/−cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His150of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.

ObjectiveDespite innovations in treatment of rheumatoid arthritis (RA), adherence is poor and disparities persist. Shared decision making (SDM) promotes patient engagement and enhances adherence; however, few tools support SDM in RA. Our objective was to pilot a low‐literacy medication guide and decision aid to facilitate patient‐clinician conversations about RA medications.MethodsRA patients were consecutively enrolled into 1 of 3 arms: 1) control; patients received existing medication guide prior to clinic visit, 2) adapted guide prior to visit, and 3) adapted guide prior to plus decision aid during visit. Outcomes were collected immediately postvisit, at 1‐week, and at 3‐ and 6‐month interviews. Eligible adults had to have failed at least 1 disease‐modifying antirheumatic drug and fulfill 1 of the following: age >65 years, immigrant, non–English speaker, less than high school education, limited health literacy, and racial/ethnic minority. Primary outcomes were knowledge of RA medications, decisional conflict, and acceptability of interventions.ResultsThe majority of 166 patients were immigrants (66%), non–English speakers (54%), and had limited health literacy (71%). Adequate RA knowledge postvisit in arm 3 was higher (78%) than arm 1 (53%; adjusted odds ratio 2.7, 95% confidence interval 1.2, 6.1). Among patients with a medication change, there was lower (better) mean decisional conflict in arms 2 and 3 (P = 0.03). There were no significant differences in acceptability.ConclusionA low‐literacy medication guide and decision aid was acceptable, improved knowledge, and reduced decisional conflict among vulnerable RA patients. Enhancing knowledge and patient engagement with decision support tools may lead to medication choices better aligned with RA patients’ values and preferences.

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.

Abstract Purpose: A prophylactic ureteral localization stent (PULSe) placed by urologists aids in intraoperative localization and detection of suspected ureteral injury during complex colorectal surgery (CRS) cases. We evaluated the incidence and management of urologic-induced complications secondary to PULSe placement during CRS cases at a single center. Materials and Methods: We performed a retrospective review of all patients who underwent cystoscopy and PULSe placement at the time of CRS over a 12-month period. Bilateral 5 French ×70-cm TigerTail ® (Bard Medical Division, Covington, GA) PULSe devices were placed without assistance of routine fluoroscopy. Results: Ninety-nine patients (mean age, 58.1 years; range, 17–88 years) underwent bilateral PULSe placement, with a male:female ratio of 44:55 and a mean body mass index of 26.8 (17.0–38.6) kg/m 2 . Mean pre- and postprocedural creatinine levels were 0.91 and 1.01 mg/dL, respectively. Twenty-two of 99 (22%) cases utilized a guidewire to aid in placement of PULSe. Four Clavien grade IIIb complications occurred: mucosal edema, reflex anuria, ureteral perforation, and ureteral obstruction secondary to significant clot burden. Three of the grade IIIb complications were managed endoscopically with double-J stent placement. The ureteral perforation case required percutaneous nephrostomy tube placement. Subgroup analysis of the four grade IIIb complications revealed a mean age of 62.3 years, body mass index of 26.98 kg/m 2 , and pre- and postprocedural creatinine levels of 0.95 and 4.83 mg/dL, respectively. Only one of the four grade IIIb complications utilized a guidewire prior to PULSe placement. Conclusions: The incidence of Clavien grade III urologic-induced complications during PULSe placement is approximately 2% (4/188). Mandatory adoption of fluoroscopy and guidewires may be required to minimize complications of PULSe placement.

Purpose: To present a rare case of disseminated intravascular coagulation (DIC) after thoracic endovascular aortic repair (TEVAR) and its novel treatment. Case Report: A 55-year-old man presented with DIC 10 months after TEVAR for chronic type B aortic dissection and descending thoracic aortic aneurysm. He had persistent retrograde flow in the false lumen with a stable aneurysm diameter. The false lumen was embolized with multiple Amplatzer plugs, which promoted false lumen thrombosis. Laboratory evaluation on postoperative day 7 demonstrated resolution of the coagulopathy. Follow-up at 18 months revealed no recurrent DIC; computed tomography angiography showed a stable aortic diameter and excluded thoracic aneurysm sac. Conclusion: This case demonstrates an unusual, potentially fatal postoperative complication of endovascular treatment of type B aortic dissections successfully treated with an innovative endovascular solution.