The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma.

The suppressor of cytokine signaling 1 (SOCS1) is a tumor suppressor gene found to be hypermethylated in cancers. It is involved in the oncogenic transformation of cirrhotic liver tissues. Here, we investigated the clinical relevance of SOCS1 methylation and modulation upon epigenetic therapy in diverse cellular populations of hepatocellular carcinoma (HCC). HCC clinical specimens were evaluated for SOCS1 methylation and mRNA expression. The effect of 5-Azacytidine (5-AZA), a demethylation agent, was assessed in different subtypes of HCC cells. We demonstrated that the presence of SOCS1 methylation was significantly higher in HCC compared to peri-HCC and non-tumoral tissues (52% vs. 13% vs. 14%, respectively, p < 0.001). In vitro treatment with a non-toxic concentration of 5-AZA significantly reduced DNMT1 protein expression for stromal subtype lines (83%, 73%, and 79%, for HLE, HLF, and JHH6, respectively, p < 0.01) compared to cancer stem cell (CSC) lines (17% and 10%, for HepG2 and Huh7, respectively), with the strongest reduction in non-tumoral IHH cells (93%, p < 0.001). 5-AZA modulated the SOCS1 expression in different extents among the cells. It was restored in CSC HCC HepG2 and Huh7 more efficiently than sorafenib. This study indicated the relevance of SOCS1 methylation in HCC and how cellular heterogeneity influences the response to epigenetic therapy.

Minimized extracorporeal circulation for the robotic totally endoscopic coronary artery bypass grafting hybrid procedure.

Robotically assisted totally endoscopic coronary artery bypass grafting (TECAB) can be performed on the beating heart with cardiopulmonary bypass support in high-risk patients or patients for whom technical difficulties are expected with a complete off-pump approach. To minimize the inflammatory response and reduce the requirement for transfusion, minimized extracorporeal circulation is an attractive option for robotic TECAB procedures. The present report describes a case for which minimized extracorporeal circulation was used for the first time in TECAB performed using the da Vinci telemanipulation system.

Toward decision support for breast reconstruction: automated calculation of symmetry measure on clinical photographs.

The quality of life of breast cancer survivors is maintained by minimizing adverse effects on their physical appearance. In this study, we present an automated method for computing a common measure of breast symmetry, the normalized Breast Retraction Assessment (pBRA), from routine clinical photographs taken to document breast reconstruction procedures.

Heart failure and "inoperable" aortic stenosis: staged balloon aortic valvuloplasty and aortic valve bypass.

The prognosis for patients with symptomatic aortic stenosis is poor but is improved significantly by surgical aortic valve replacement. Unfortunately, many patients are refused surgery because of age, comorbidities, and hemodynamic instability. This report describes the successful use of balloon aortic valvuloplasty as a bridge to aortic valve bypass surgery (apicoaortic conduit) in an elderly patient with class IV congestive heart failure and severe left ventricular systolic dysfunction as a consequence of aortic stenosis who was not a candidate for traditional surgical valve replacement.

Simultaneous "hybrid" percutaneous coronary intervention and minimally invasive surgical bypass grafting: feasibility, safety, and clinical outcomes.

Surgical and percutaneous coronary artery intervention revascularization are traditionally considered isolated options. A simultaneous hybrid approach may allow an opportunity to match the best strategy for a particular anatomic lesion. Concerns regarding safety and feasibility of such an approach exist. We examined the safety, feasibility, and early outcomes of a simultaneous hybrid revascularization strategy (minimally invasive direct coronary bypass grafting of the left anterior descending [LAD] artery and drug-eluting stent [DES] to non-LAD lesions) in 13 patients with multivessel coronary artery disease that underwent left internal mammary artery to LAD minimally invasive direct coronary bypass performed through a lateral thoracotomy, followed by stenting of non-LAD lesions, in a fluoroscopy-equipped operating room. Assessment of coagulation parameters was also undertaken. Inhospital and postdischarge outcomes of these patients were compared to a group of 26 propensity score matched parallel controls that underwent standard off-pump coronary artery bypass. Baseline characteristics were similar in both groups. All hybrid patients were successfully treated with DES and no inhospital mortality occurred in either group. Hybrid patients had a shorter length of stay (3.6 +/- 1.5 vs 6.3 +/- 2.3 days, P < .0001) and intubation times (0.5 +/- 1.3 vs 11.7 +/- 9.6 hours, P < .02). Despite aggressive anticoagulation and confirmed platelet inhibition, hybrid patients had less blood loss (581 +/- 402 vs 1242 +/- 941 mL, P < .05) and decreased transfusions (0.33 +/- 0.49 vs 1.47 +/- 1.53 U, P < .01). Six-month angiographic vessel patency and major adverse cardiac events were similar in the hybrid and off-pump coronary artery bypass groups. A simultaneous hybrid approach consisting of minimally invasive coronary artery bypass grafting with left internal mammary artery to LAD combined with revascularization of the remaining coronary targets using percutaneous coronary artery intervention with DES is a feasible option accomplished with acceptable clinical outcomes without increased bleeding risk.

Surgery for severe mitral regurgitation and left ventricular failure: what do we really know?

In ischemic and nonischemic cardiomyopathy, functional mitral regurgitation (MR) results from geometric abnormalities of the ventricle, which result in dysfunction of a morphologically normal mitral valve. Enlargement of the left ventricle causes geometric MR through annular dilation, increase in the interpapillary muscle distance, amplified leaflet tethering (elongation and stretch on the chordae tendinae), and decreased closing forces because of muscle weakness and asynchrony of papillary muscle contractile timing. The final common pathway of MR is a failure of coaptation of the morphologically normal leaflets and resultant central MR. These abnormalities can be favorably influenced by antiremodeling pharmacologic therapy and in selected cases by cardiac resynchronization therapy. Surgical repair of functional geometric MR with an undersized complete rigid annuloplasty ring can abolish MR and is associated with improved functional status and left ventricular remodeling. It is unclear if surgery is associated with improved survival in this setting. There is a pressing need for well-conducted prospective randomized clinical trials to quantify the benefits of surgical repair of functional geometric MR.

A hybrid alternative for high risk left main disease.

Percutaneous revascularization strategies for bifurcation disease of the left main are complex and carry significant risk. These risks are magnified in the setting of a left main which trifurcates. In a patient with complex ostial disease of two of the three limbs of a left main trifurcation, turned down for conventional bypass surgery, we report on a hybrid approach for complete revascularization, consisting of minimally invasive bypass grafting of the LAD combined with simultaneous drug eluting stent placement.