A B S T R A C T PurposeSentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND). Patients and MethodsAt median follow-up of 5 years, lymphedema was assessed in 936 women with clinically nodenegative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined. ResultsOf the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P Ͻ .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P Ͻ .0001). Risk factors associated with measured lymphedema were greater body weight (P Ͻ .0001), higher BMI (P Ͻ .0001), and infection (P Ͻ .0001) or injury (P ϭ .02) in the ipsilateral arm since surgery. ConclusionWhen compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.

A B S T R A C T PurposeSentinel lymph node (SLN) biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. This study was undertaken to examine patient perceptions of lymphedema and use of precautionary behaviors several years after axillary surgery. Patients and MethodsNine hundred thirty-six women who underwent SLN biopsy (SLNB) alone or SLNB followed by axillary lymph node dissection (SLNB/ALND) between June 1, 1999, and May 30, 2003, were evaluated at a median of 5 years after surgery. Patient-perceived lymphedema and avoidant behaviors were assessed through interview and administered a validated instrument, and compared with arm measurements. ResultsCurrent arm swelling was reported in 3% of patients who received SLNB alone versus 27% of patients who received SLNB/ALND (P Ͻ .0001), as compared with 5% and 16%, respectively, with measured lymphedema. Only 41% of patients reporting arm swelling had measured lymphedema, and 5% of patients reporting no arm swelling had measured lymphedema. Risk factors associated with reported arm swelling were greater body weight (P Ͻ .0001), higher body mass index (P Ͻ .0001), infection (P Ͻ .0001), and injury (P ϭ .007) in the ipsilateral arm since surgery. Patients followed more precautions if they had measured or perceived lymphedema. ConclusionBody weight, infection, and injury are significant risk factors for perceiving lymphedema. There is significant discordance between the presence of measured and patient-perceived lymphedema. When compared to SLNB/ALND, SLNB-alone results in a significantly lower rate of patientperceived arm swelling 5 years postoperatively, and is perceived by fewer women than are measured to have it. J Clin

The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins. We next analyzed FXR-Gank-Tumor suppressor pathways in a large cohort of HBL patients which include 6 controls and 53 HBL samples. Systemic analysis of these samples and RNA-Seq approach revealed that the FXR-Gank axis is activated; markers of hepatic stem cells are dramatically elevated and hepatocyte markers are reduced in HBL samples. In the course of these studies, we found that RNA binding protein CUGBP1 is a new tumor suppressor protein which is reduced in all HBL samples. Therefore, we generated CUGBP1 KO mice and examined HBL signatures in the liver of these mice. Micro-array studies revealed that the HBL-specific molecular signature is developed in livers of CUGBP1 KO mice at very early ages. Thus, we conclude that FXR-Gank-TSPs-Stem cells pathway is a key determinant of liver cancer in animal models and in pediatric liver cancer. Our data provide a strong basis for development of FXR-Gank-based therapy for treatment of patients with hepatoblastoma.

Hepatoblastoma (HBL) is a pediatric liver cancer that affects children under the age of three. Reduction of tumor suppressor proteins (TSPs) is commonly seen in liver cancer. However, in our studies we find that aggressive, chemo-resistant HBLs exhibit an elevation of TSPs. HBL patients with a classic phenotype have reduced TSP levels, but patients with aggressive HBL express elevated TSPs that undergo posttranslational modifications, eliminating their tumor suppression activities. Here we identify unique aggressive liver cancer domains (ALCDs) that are activated in aggressive HBL by PARP1-mediated chromatin remodeling leading to elevation of modified TSPs and activation of additional cancer pathways: WNT signaling and β-catenin. Inhibition of PARP1 blocks activation of ALCDs and normalizes expression of corresponding genes, therefore reducing cell proliferation. Our studies reveal PARP1 activation as a mechanism for the development of aggressive HBL, further suggesting FDA-approved PARP1 inhibitors might be used for treatment of patients with aggressive HBL.

Summary The development of Non Alcoholic Fatty Liver Disease (NAFLD) is a multiple step process. Here we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and HCC. The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high fat diet (HFD)-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, these studies reveal that activation of cdk4 triggers NAFLD, and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.

The earliest steps of adult HCC and aggressive pediatric liver cancer have identical features that include conversion of the tumor suppressor C/EBPα into an oncogenic isoform, which further creates preneoplastic foci where hepatocytes dedifferentiate into cancer cells, giving rise to liver cancer. (Hepatology 2018;67:1857-1871).

This study shows that administrative data have copious omissions of specific injuries, diagnostic and therapeutic interventions, as well as complications. The trauma registry recorded more of the diagnoses, diagnostics, procedures, and outcomes in the care of trauma patients. Trauma registries may be more useful than administrative databases in assessing quality of care and diagnostic and therapeutic interventions.

Surgical resident experience on most trauma services is heavily weighted to nonoperative management, with a relatively low number of procedures, little experience with DPL, and highly variable experience with ultrasound. These data have serious implications for resident training and recruitment into the specialty.