Transhiatal esophagectomy in the profoundly obese: implications and experience.

BACKGROUND: Historically, obesity contraindicated an abdominal approach to the esophagogastric junction. The technique of transhiatal esophagectomy (THE) evolved without specific regard to body habitus. The dramatic increase in obese patients requiring an esophagectomy for complications of reflux disease prompted this evaluation of the impact of obesity on the outcomes of esophagectomy to determine whether profound obesity should contraindicate the transhiatal approach. METHODS: We used our Esophagectomy Database to identify 133 profoundly obese patients (body mass index [BMI] > or = 35 kg/m2) from among 2176 undergoing a THE from 1977 to 2006. This group was matched to a randomly selected, non-obese (BMI, 18.5 to 30 kg/m2) control population of 133 patients. Intraoperative, postoperative, and long-term follow-up results were compared retrospectively. RESULTS: Profoundly obese patients had significantly greater intraoperative blood loss (mean, 492.2 mL versus 361.8 mL, p = 0.001), need for partial sternotomy (18 versus 3, p = 0.001), and frequency of recurrent laryngeal nerve injury (6 versus 0, p = 0.04). The two groups did not differ significantly in the occurrence of chylothorax, wound infection, or dehiscence rate; length of hospital stay or need for intensive care unit stay; or hospital or operative mortality. Follow-up results for dysphagia, dumping, regurgitation, and overall functional score were also comparable between the two groups. CONCLUSIONS: With appropriate instrumentation, transhiatal esophagectomy in obese patients has similar morbidity and outcomes as in non-obese patients. Obesity, even when profound, does not contraindicate a transhiatal esophagectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/6/Scipione 2007.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/5/Benign BMI Control.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/4/Benign BMI CS07.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/3/CA BMI Control no pt id.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/2/CA BMI 35 CS.tx

The effects of stimulants and depressants on cocaine self-administration behavior in the Rhesus monkey

The effects of acute intramuscular pretreatment with several dosages of a variety of centrally acting compounds on intravenous cocaine self-administration behavior were ascertained. Pretreatment with morphine and pentobarbital produced no change in this behavior until dosages (2.0 mg/kg and 15.0 mg/kg respectively) were administered which grossly depressed grooming, exploratory, and locomotor activity behaviors, d -amphetamine (0.5–4.0 mg/kg) and phenmetrazine (2.0–12.0 mg/kg) pretreatment produced a dose-related decrease in cocaine self-administration. Trifluoperazine in dosages of 0.01–0.1 mg/kg increased the frequency of this behavior; whereas, higher dosages (0.2, 0.4 mg/kg) grossly depressed behavior. Imipramine (10–50 mg/kg) produced a dose-related decrease in cocaine self-administration. Potential mechanisms of these drug—behavior and drug—drug interactions are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46388/1/213_2004_Article_BF00421274.pd

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Identification and validation of novel biomarkers and therapeutics for pulpitis using connectivity mapping

International audienceAim To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. Methodology The Gene Expression Omnibus (GEO) database, an international public repositor

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN