A systematic review and meta-analysis of the utility of repeated versus single hepatic resection for colorectal cancer liver metastases

Background

Recurrence of colorectal liver metastases after a first hepatectomy is common (4–48% of patients). This review investigates the utility of repeated hepatic resection of colorectal liver metastases.

Immunohistochemical profiling of liver metastases and matched-pair analysis in patients with metastatic pancreatic ductal adenocarcinoma

BackgroundThe purpose of the current study was to investigate the immunohistochemical (IHC) profile of liver metastases (LM) in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsExpression of 15 IHC markers in liver biopsies from 77 patients with PDAC, who were diagnosed between 2010 and 2014, were evaluated. In a separate subgroup analysis (n = 12), paired samples (LM and primary tumor) from the same patient were investigated for IHC profile differences.ResultsLM samples were classified as pancreatobiliary-type (PB-type) in 72 patients (93.5%), intestinal-type (INT-type) in four patients (5.2%), and squamous in one patient (1.3%). There was no significant difference in overall survival (OS) between LM of the PB-type or INT-type (p = 0.097). In a multivariate analysis, age <70 years (p = 0.047), absence of SMAD4 mutation (p = 0.026), absence of CDX2 expression (p = 0.003), and well to moderate differentiation were significant prognostic factors for better OS in patients with LM (p = 0.031). Analysis of paired tissue samples from LM and the primary tumor revealed a difference in CDX2 (50% increase, p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375).ConclusionsCDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC. Matched-pair analysis revealed differences in distinct IHC marker expression.     

Dissociation between in vivo and in vitro measurements of converting enzyme activity after chronic oral treatment with captopril in rats

Intravenous administration of captopril (20 micrograms) produced inhibition of angiontensin I pressor responses by 70 percent and of plasma-converting enzyme activity by 72 percent. Oral treatment with captopril (50 mg/kg/day) for 1 week inhibited angiotensin I pressor responses more (84 percent) than plasma-converting enzyme activity (23 percent). Four month oral treatment of normotensive and spontaneously hypertensive rats with captopril (50 mg/kg/day) led to 68 and 71 percent inhibition of angiotensin I pressor responses, but produced increases in plasma-converting enzyme activity of 123 and 94 percent, respectively. In spontaneously hypertensive rats, elevated converting enzyme activity in the medulla oblongata was measured after this treatment. It is concluded that plasma-converting enzyme activity measurements can be dissociated from the in vivo inhibition of converting enzyme. Chronic oral captopril treatment results in an induction of converting enzyme biosynthesis not only in peripheral tissue but also in the brain.     

Left Ventricular Strain in Chemotherapy-Naive and Radiotherapy-Naive Patients With Cancer

Background

We sought to investigate left ventricular (LV) function and mechanics in patients with cancer before they received chemotherapy or radiotherapy, as well as the relationship between cancer and reduced LV multidirectional strain in the whole study population.

Contrary to Expectations: Off-Label Transcatheter Aortic Valve Replacement in the Case of Left Ventricular Outflow Tract Obstruction

We present the case of a 71-year-old woman who showed recurrent signs of congestive heart failure with the need of rehospitalization after double valve (mitral and aortic) replacement. Extensive diagnostic workup revealed a moderate aortic stenosis and additionally a significant left ventricular outflow tract obstruction. The tissue overgrowth might be attributed to an inflammatory reaction with extensive pannus deposit after aortic valve surgery. With no-option for re-do surgery we performed the first-in-man off-label valve-in-left ventricular outflow tract procedure with an Edwards Sapien III 23 mm in deep orientation.     

The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Postconditioning

Background

Remote ischemic postconditioning (RIPostC) could reduce myocardial ischemia/reperfusion injury markedly. However, the mechanism of the protective signal transfer of RIPostC to the heart remains unclear. In this study, we hypothesize that macrophage migration inhibitory factor (MIF) plays an important role in the cardioprotection conferred by RIPostC.

Hybrid Melody Valve Implantation in Mitral Position in a Child: Usefulness of a 3-Dimensional Printed Model for Preprocedural Planning

We present the case of a 4-month-old child with atrioventricular canal associated with severe left atrioventricular valve dysfunction who previously underwent 3 surgical valve reconstructions without significant improvement. A Hybrid Melody valve (Medtronic, Minneapolis, MN) insertion was planned. Because of the low weight, the risk of left ventricular outflow tract obstruction was significant and therefore evaluated preprocedurally using a cardiac computed tomography-derived 3-dimensional printed model. In vitro tests showed good anchorage of the valve without subaortic obstruction and the procedure was then achieved with an excellent clinical result.     

Importance of Risk Reassessment in Patients With Atrial Fibrillation in Guidelines: Assessing Risk as a Dynamic Process

The appropriate use of oral anticoagulants (OACs) for prevention of stroke in atrial fibrillation (AF) relies on the convenient and accurate stroke risk-prediction scheme: namely, the CHA₂DS₂-VASc score. As patients with AF would become older and accumulate more comorbidities, their risks—for example, as reflected by the CHA₂DS₂-VASc scores—are not static and could increase over time. The available data demonstrated that follow-up and Δ CHA₂DS₂-VASc scores perform better than the baseline CHA₂DS₂-VASc score in the prediction of ischemic stroke. Approximately 90% of initially low-risk patients would have a Δ CHA₂DS₂-VASc score ≥ 1 before the occurrence of ischemic stroke. Apart from risk of stroke, the risk of bleeding for patients with AF is also highly dynamic. For example, the accuracies of the follow-up or Δ Hypertension, Abnormal Renal and Liver Function, Stroke, Bleeding, Labile INR, Elderly, Drugs or Alcohol (HAS-BLED) score in the prediction of major bleeding was significantly higher than that of the baseline HAS-BLED score. Most importantly, the risks of stroke and major bleeding were higher within several months after patients had changes (increases) in their stroke- or bleeding-risk scores. Therefore, risk profiles of patients with AF should be reassessed regularly so that OACs could be prescribed in a timely manner once patients are no longer at low risk for stroke, and modifiable risk factors for bleeding could be corrected. More efforts are necessary to incorporate clear and easy-to-follow recommendations about risk reassessment into the guidelines to improve AF patient care.     

Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart Failure

ObjectivesTo evaluate possible treatment-related hemodynamic changes, we administered ranolazine or mexiletine to swine with heart failure (HF) and to controls.BackgroundRanolazine and mexiletine potently inhibit depolarizing late Na⁺ current (I_Na,late) and Na⁺ entry into cardiomyocytes_. Blocking Na⁺ entry may increase forward-mode Na/Ca exchange and reduce cellular Ca⁺² load, further compromising systolic contraction during HF.Methods and ResultsAnesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine (n = 7) as boluses, then as infusions; the same experiments were performed in 10 nonpaced controls. The swine with HF had characteristic elevated left ventricular end-diastolic pressure (LVEDP) and reduced maximal left ventricular pressure rise (+dP/dt_max) and left ventricular peak systolic pressure (LVSP). No significant change occurred after ranolazine dosing for any parameter: LVEDP, +dP/dt_max, LVSP, heart rate, maximal LV pressure fall rate (–dP/dt_max), or time constant for isovolumic relaxation. Similar results seen in additional swine with HF: 7 were given mexiletine, and 7 others were given ranolazine after a 27% rate decrement to maximize I_Na,late. Patch-clamped HF cardiomyocytes confirmed drug-induced I_Na,late blockade.ConclusionsRanolazine or mexiletine blocking I_Na,late neither worsened nor improved hemodynamics during advanced HF. Although results must be clinically confirmed, they suggest inhibition of I_Na,late by ranolazine or mexiletine may not exacerbate HF in patients.     

Prognostic Impact of Worsening Renal Function in Hospitalized Heart Failure Patients With Preserved Ejection Fraction: A Report From the JASPER Registry

BackgroundThe characteristics and prognostic impact of persistent worsening renal function (WRF; defined as an increase in serum creatinine of >0.3 mg/dL during hospitalization) on heart failure with preserved ejection fraction have not yet been fully examined.Methods and ResultsThis was a post hoc analysis of the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry. We divided 523 patients with heart failure with preserved ejection fraction: the WRF group (n = 92 [17.6%]) and the non-WRF group (n = 431 [82.4%]). The WRF group showed a higher systolic blood pressure on admission and a higher prevalence of atherosclerotic diseases, respectively. Logistic regression analysis revealed that systolic blood pressure and loop diuretics were associated with WRF development (P < .05). The Kaplan-Meier analysis (median, 732 days) showed a higher all-cause death in the WRF group, as well as a higher composite end point of all-cause death or rehospitalization for HF (log-rank P < .001). The Cox proportional hazard analysis revealed WRF to be a predictor of both all-cause death (hazard ratio, 2.725; 95% confidence interval, 1.709–4.344; P < .001) and the composite end point (hazard ratio, 2.083; 95% confidence interval, 1.488–2.914; P < .001).ConclusionsPersistent WRF was associated with systolic blood pressure, atherosclerotic diseases, diuretics, and poor postdischarge prognosis in patients with heart failure with preserved ejection fraction.     

High fat diet downregulates regulatory T cells in the myocardium of spontaneous hypertensive rats

Background and aimRegulatory T cells (Tregs) play an important role in cardiovascular complications with the immune response. However, the role of Tregs in high fat diet (HFD)-induced myocardial fibrosis has not been fully elucidated to date. Therefore, we investigated whether HFD suppresses Tregs activation in the myocardium of spontaneously hypertensive rats (SHRs), which aggregates myocardial fibrosis.Methods and resultsEight-week-old male SHRs were fed to either HFD or control diet (CHO) groups for 12 weeks. We measured Tregs (CD4+FoxP3+) in the heart and mediastinal lymph nodes (LNs). The flow cytometry analysis confirmed that SHR-HFD exhibited a decreased Tregs compared to that of SHR-CHO in the heart and mediastinal LNs. Furthermore, the CD4 and FoxP3 antigens were used in the immunofluorescence microscopy of Tregs in the heart tissues. In the heart, dual staining for the Treg population was increased more in SHR-CHO than it was in SHR-HFD rats. In line with these findings, SHR-HFD significantly exacerbated myocardial fibrosis.ConclusionWe found that diet-induced obesity typically showed an exacerbated myocardial fibrosis and down-regulation of Tregs pathway in the heart and mediastinal LNs. Therefore, we suggest that the up-regulation of Tregs may be a promising therapeutic approach to preventing obesity induced heart failure.