Oncoplastic Breast Surgery

Breast Surgery is now a recognized subspecialty of General Surgery abroad with structured training for designated ‘Oncoplastic Breast Surgeons’. Oncoplastic Breast surgery is probably one of the most interesting and challenging new developments over the past 20 years. The aims of Oncoplastic surgery are wide local excision of the cancer coupled with partial reconstruction of the defect to achieve a cosmetically acceptable result. Avoidance of mastectomy and consequent reduction of psychological morbidity are the principal goals in the development of various oncoplastic techniques. The use of plastic surgical techniques not only ensures good cosmetic outcome, but also allows the cancer surgeon to remove the tumour with greater volume of surrounding tissue, thus extending the boundaries of breast conserving surgery. Proper patient selection and careful planning after proper radiological and clinical assessment are the two essential prerequisites before undertaking oncoplastic breast surgery. Oncoplastic surgery involves both volume displacement and volume replacement techniques. Some commonly used volume displacement procedures are described in the article. The need for adjustment of contralateral breast should also be anticipated at the time of planning breast conserving surgery, which can be done either at the same time as breast cancer surgery or as a delayed setting.     

Relationship between complex fractionated electrograms (CFE) and dominant frequency (DF) sites and prospective assessment of adding DF-guided ablation to pulmonary vein isolation in persistent atrial fibrillation (AF)

Dominant Frequency Mapping and Ablation . Background: Sites of high DF are potential targets for AF ablation, but it is unknown if addition of DF ablation can improve procedural outcome. Objectives: We sought to (1) examine the relationship between DF sites and complex fractionated electrograms (CFE) and (2) prospectively assess the long‐term outcome of adding DF ablation to pulmonary vein antral isolation (PVAI) for persistent AF. Methods: First, 20 patients with persistent AF who underwent previous CFE‐guided ablation and who had AF terminate during ablation were studied retrospectively (group I). Bipolar, 8‐second electrograms were collected by a circular catheter (288 ± 86 points/map). The EnSite NavX system allows for automated display of both CFE and DF maps. Electrograms with cycle length <120 ms were considered CFE and were compared to DF sites > 8 Hz (direct inverse relationship). Sites of AF termination were related to CFE and DF sites. Based on these observations, 30 different patients (group II) with persistent AF prospectively underwent DF‐guided ablation plus PVAI. They were followed every 3 months for 1 year (visit, Holter, ECG). These patients were compared to case‐matched controls undergoing PVAI alone (group III). Results: In group I, there was a significant, inverse correlation between DF and CFE values at each point (r =–0.24, P < 0.001). DF surface area was less than CFE area (27 ± 5 cm² vs 34 ± 4 cm², P = 0.03). CFE sites overlapped 48 ± 27% with the DF surface area. Nonoverlapping CFE sites were contiguous to DF sites. AF termination occurred where DF and CFE overlapped, and at these sites, DF was always greater than the mean DF for the map. In group II, all DF sites above the mean value were prospectively ablated during AF. AF termination was noted in only 2/30 (7%) patients. After DF ablation, PVAI was performed and termination increased to 4/30 patients (14%). At 1 year, freedom from atrial arrhythmia > 30 seconds occurred in 57% of DF+PVAI compared to 60% in patients receiving PVAI alone (P = 0.18). Conclusions: DF and CFE regions overlap only about 50%. AF termination retrospectively occurred on overlapping CFE/DF sites where DF was above the mean. However, prospective ablation of DF sites plus PVAI resulted in low AF termination rates, and did not improve 1 year success over PVAI alone. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1309‐1316, December 2011)     

Outcomes of junctional ectopic tachycardia ablation in adult population—a multicenter experience

Purpose

Idiopathic junctional ectopic tachycardia (JET) is typically refractory to antiarrhythmic agents. Catheter ablation for JET is feasible but is associated with high risk of unintended atrioventricular (AV) block. There is limited data on the appropriate procedural technique and clinical outcomes with catheter ablation for idiopathic JET in adults.

Methods

This is a multicenter, retrospective study of all adult patients (age?≥?18 years) who underwent catheter ablation for idiopathic JET. Patient, procedural characteristics, and long-term outcomes were evaluated.

Results

Fifteen patients [radiofrequency ablation (RF)?=?14 and cryoablation?=?1) were treated with catheter ablation. The median age was 58 years with 67% males. All patients underwent mapping of the right atrium and the aortic cusps prior to energy delivery. The location of earliest activation in relation to the atrioventricular (AV) node was postero-superior in 73% (11/15), posterior in 13% (2/15), and superior in 13% (2/15) respectively. Acute success was 100%. Arrhythmia recurrence occurred in 53% (8/15) all of whom underwent a repeat ablation. High-grade AV block requiring permanent pacemaker occurred in 20% (3/15). At 12-month follow-up in the redo-ablation group, 37.5% (3/8) had recurrence of the arrhythmia two of which underwent a third ablation procedure.

Conclusion

Catheter ablation of idiopathic JET in adults is associated with a high rate of recurrence requiring multiple procedures and high risk of AV block requiring a permanent pacemaker. Mapping and ablation of the non-coronary cusp can be considered as the arrhythmia was controlled in 3 patients with no inadvertent AV block.

     

Potentiation of platelet activation through the stimulation of P2X1 receptors

Summary.  The platelet P2X₁ purinergic receptor is a ligand-gated ion channel that responds to ATP. The precise role of P2X₁ in platelet function is unknown, though stimulation with the P2X₁ agonist α,β-Me-ATP is known to result in platelet shape change through elevation of calcium levels. The aim of the present study was to examine further the effects of P2X₁ stimulation on platelet activation. Stimulation of P2X₁ with α,β-Me-ATP resulted in shape change and small aggregate formation in heparin-anticoagulated platelet preparations. Given the ability of heparin to potentiate platelet activation, subsequent experiments were performed in hirudin. In these platelet preparations, aggregate formation in response to α,β-Me-ATP alone was less than that observed in heparin; however, α,β-Me-ATP significantly potentiated platelet aggregate formation when added in conjunction with other weak platelet agonists [epinephrine or thrombopoietin (TPO)]. Platelet aggregate formation was confirmed by single platelet loss (microaggregate formation), microscopy, and light transmittance studies. Further, the P2X₁ antagonist MRS-2159 inhibited platelet shape change and aggregation responses induced by α,β-Me-ATP. Overall, this study demonstrates that P2X₁ stimulation can induce/potentiate platelet activation in combination with other platelet agonists. These results are the first demonstration of platelet aggregation mediated through direct P2X₁ stimulation, supporting a role for this receptor in regulating platelet activation.     

Thematic issue-topic--diabetic cardiovascular disease--an unmet medical need: emerging targets and therapies-introduction to the special issue

The major cause of death and complications in patients with type 2 diabetes is cardiovascular disease. Cardiovascular complications that are often associated with diabetes include heart failure, acute myocardial infarction (MI), peripheral vascular disease, and cerebrovascular disease. More than 60% of all patients with type 2 diabetes die of cardiovascular disease, and an even greater percentage have serious complications. The impact of glucose lowering on cardiovascular complications is a hotly debated issue and recent large clinical trials, the Action in Diabetes and Vascular Disease (ADVANCE), Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial (VADT) reported no significant decrease in cardiovascular events with intensive glucose control. Risk remains high even after correcting diabetes-associated dyslipidemia (high triglycerides and low HDL). Several mechanisms are likely to contribute to the accelerated atherosclerosis and increased cardiovascular disease risk seen in type 2 diabetics. Of these, postprandial hyperglycemia/lipemia, insulin resistance and inflammation may be the most important and under controlled contributing factors to vascular disease. The goal of this thematic issue is to address limitations of current therapies and review emerging research and therapeutic approaches that target inflammation, insulin resistance and other pathological mechanisms that contribute to cardiovascular disease in diabetes.     

Immunohistochemistry of hepatocellular carcinoma associated with cirrhosis

Tumor cell marker antibodies were used to analyze ten cases of hepatocellular carcinoma associated with cirrhosis. Clinically, eight of these cases gave a history of chronic alcoholism and the other two of hepatitis B virus infection. Formalin-fixed, paraffin-embedded sections from these cases were screened with antibodies against alpha fetoprotein (AFP), hepatitis B surface antigen (HBsAg) and carcinoembryonic antigen (CEA) using the peroxidase antiperoxidase and avidin-biotin immunoperoxidase procedures. Three cases were positive for AFP, four for HBsAg, and three for CEA; two cases had both HBsAg and CEA. Alpha fetoprotein was present only in the cytoplasm of tumor cells in three cases. Hepatitis B surface antigen, on the other hand, was present in the cytoplasm of hepatocytes in cirrhotic areas and, in one out of the four cases, was also present in hepatocellular carcinoma cells. Carcinoembryonic antigen was seen in three cases; it was present on the surface and in the cytoplasm of proliferating ducts within the cirrhotic areas and between cell surfaces of individual tumor cells in two cases. The presence of different markers was not related to the microscopic appearance of the tumors. In one case, positivity for AFP was of diagnostic help in a tissue sample obtained by needle biopsy. The avidin-biotin immunoperoxidase procedure was more sensitive than the peroxidase antiperoxidase (PAP technique in the pathological assessment of autopsy specimens. Our findings are in agreement with those of other reports and indicate that AFP and HBsAg are the most commonly found markers in hepatoma associated with cirrhosis, and that CEA staining is variable and hepatoma associated with cirrhosis, and that CEA staining is variable and probably non-contributory.     

Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1alpha: implications for development of selective CXCR4 antagonists

The C-X-C chemokine SDF-1 and its receptor CXCR4, mediate a pivotal role in the pathophysiology of HIV-1 infection and vascular inflammatory diseases. In this study, we investigated the pharmacological properties of SDF-1alpha interaction with CXCR4 in human leukemia cell lines. Our data, based on [125I]-SDF-1alpha radioligand binding, SDF-1alpha-induced [35S]-GTPgammaS binding and use of specific CXCR4 antagonist AMD3100 reveals the complex nature of SDF-1alpha-CXCR4 interaction. Firstly, homologous competition with cold SDF-1alpha revealed a bimodal ligand displacement curve and secondly, although AMD3100 inhibited both SDF-1alpha-mediated chemotaxis (IC(50)=4.7 nM) and [35S]-GTPgammaS binding (IC(50)=7.4 nM) with high affinity, it was intriguingly up to 3000-fold less potent (IC(50)=15.2 microM) in the radioligand binding assay. These results provide pharmacological evidence for the recently described two-site model for SDF-1alpha-CXCR4 interaction. Accordingly, inhibition of SDF-1alpha binding to one of the receptor sites is sufficient to antagonize function, without causing its complete displacement from the receptor. Furthermore, these findings have important implications in the development and evaluation of CXCR4-selective small molecule antagonists for therapeutic use.     

Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES)

The aim of this cross-sectional study was to assess the association of insulin resistance (IR) with inflammatory molecules C-reactive protein (CRP), interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic protein 1 (MCP-1) in urban South Indian subjects. The following groups were selected from the population-based Chennai Urban Rural Epidemiology Study: group 1 composed of 50 healthy subjects with normal glucose tolerance without IR; group 2 consisted of 50 normal glucose-tolerant subjects with IR as defined by homeostasis model assessment of IR (HOMA-IR); group 3 consisted of 50 subjects with impaired glucose tolerance (IGT); and groups 4 and 5 each comprised 50 newly diagnosed and known type 2 diabetic subjects, respectively. The inclusion criteria included nonsmokers; normal resting 12-lead electrocardiogram; and absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases, and not on statins or aspirin. Normal glucose tolerance without IR had the lowest values of CRP, IL-6, and VCAM-1 (CRP, 1.32 mg/L; IL-6, 12.56 pg/mL; VCAM-1, 277 pg/mL) followed by normal glucose tolerance with IR (CRP, 2.25 mg/L; IL-6, 20.97 pg/mL; VCAM-1, 289 pg/mL), impaired glucose tolerance (CRP, 2.37 mg/L; IL-6, 22.11 pg/mL; VCAM-1, 335 pg/mL), newly diagnosed diabetic subjects (CRP, 3.24 mg/L; IL-6, 23.21 pg/mL; VCAM-1, 568 pg/mL), and the highest levels were in the known diabetic subjects (CRP, 4.08 mg/L; IL-6, 29.44 pg/mL; VCAM-1, 577 pg/mL). This trend was statistically significant (P < .001). However, monocyte chemotactic protein 1 did not show such a trend and did not differ significantly between groups. In nondiabetic subjects, Pearson correlation analysis revealed that CRP (r = 0.299; P < .001) and IL-6 (r = 0.180, P = .025) had a significant correlation with HOMA-IR. Monocyte chemotactic protein 1 did not show any correlation with HOMA-IR. Multiple linear regression analysis revealed CRP to be significantly associated with HOMA-IR (beta = .229; P < .001) and this was unaltered by the addition of waist and IL-6 into the model (beta = .158; P = .028). In conclusion, this study shows that in Asian Indians, inflammatory markers (CRP, IL-6, and VCAM-1) increase with increasing degrees of glucose intolerance.