Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas,adenocarcinomas and squamous cell carcinoma cell lines

Dipeptidyl peptidase IV (DPPIV) is a transmembrane serine protease which is involved in the process of tumor invasion and development of metastases in human cancers. The aim of this study was to investigate the expression of DPPIV in cancer and stromal cells of both esophageal adenocarcinoma and squamous cell carcinoma (SCC). Tissue material from 159 patients was analyzed using immunohistochemistry. Western blotting was performed on cell lines and fresh frozen tissue sections. Results were compared with clinicopathological features. Evaluation of the immunohistochemical findings revealed significant differences between DPPIV expression in carcinoma cells and stromal cells, depending on the histological tumor type. A significantly higher level of DPPIV was found in adenocarcinomas compared to SCCs while no DPPIV was detected in normal esophageal epithelium. Overexpression of DPPIV in patients with adenocarcinoma was additionally associated with distant metastases. Thus, differences of DPPIV level in esophageal carcinomas compared with normal epithelium showed that esophageal malignancies were associated with an increased amount of cell surface‐bound DPPIV. Radiotherapy in patients had no impact on DPPIV expression in analyzed tissue samples. There was no correlation between DPPIV expression in cancer or stromal cells and survival of the patients.     

Effect of Therapeutic Ionizing Radiation on Implantable Electronic Devices: Systematic Review and Practical Guidance

Cardiac implantable electronic devices (CIEDs) have been in use for over 50 years and their therapeutic value is undisputable. With the rapidly aging population, it is estimated that the number of CIEDs will grow dramatically over the next 2 decades. Given these predictions, the topic of management of concomitant conditions associated with older age becomes more relevant than ever. In particular, the number of patients with an implanted CIED diagnosed with cancer is expected to rise by about 70%, from 14 million in 2012 to 22 million within the next 2 decades. Treatment of most of these tumors and tumor metastases requires radiation therapy. However, the necessary high doses of radiation can potentially interact with the function, longevity, and integrity of the CIEDs and/or cause harm to the patient. The impact of an absence of clear therapeutic guidelines for oncology patients with CIEDs who should undergo radiation therapy is vast; and due to the fear of possible complications related to device failure, many of these patients may not be treated adequately to their needs, which can strongly affect their prognosis. This article summarizes the available data on the management of patients with CIEDs undergoing radiotherapy. It systematically presents possible causes and consequences of direct and scattered radiation on CIEDs, highlights possible complications that may occur during this kind of treatment, and provides practical guidance for this challenging real life clinical setting.     

Ablation of Severe Drug‐Resistant Tachyarrhythmia During Pregnancy

Ablation of Tachyarrhythmia During Pregnancy. Aims: The goal of this study was to describe mapping and ablation of severe arrhythmias during pregnancy, with minimum or no X‐ray exposure. Treatment of tachyarrhythmia in pregnancy is a clinical problem. Pharmacotherapy entails a risk of adverse effects and is unsuccessful in some patients. Radiofrequency ablation has been performed rarely, because of fetal X‐ray exposure and potential maternal and fetus complications. Group and Method: Mapping and ablation was performed in 9 women (age 24–34 years) at 12–38th week of pregnancy. Three had permanent junctional reciprocating tachycardia, and 2 had incessant atrial tachycardia. Four of them had left ventricular ejection fraction ≤45%. One patient had atrioventricular nodal reciprocating tachycardia requiring cardioversion. Three patients had Wolff‐Parkinson‐White syndrome. Two of them had atrial fibrillation with ventricular rate 300 bpm and 1 had atrioventricular tachycardia 300 bpm. Fetal echocardiography was performed before and after the procedure. Results: Three women had an electroanatomic map and ablation done without X‐ray exposure. The mean fluoroscopy time in the whole group was 42 ± 37 seconds. The mean procedure time was 56 ± 18 minutes. After the procedure, all women and fetuses were in good condition. After a mean period of 43 ± 23 months follow up (FU), all patients were free of arrhythmia without complications related to ablation either in the mothers or children. Conclusion: Ablation can be performed safely with no or minimal radiation exposure during pregnancy. In the setting of malignant, drug‐resistant arrhythmia, ablation may be considered a therapeutic option in selected cases. (J Cardiovasc Electrophysiol, Vol. 21, pp. 877‐882, August 2010)     

Programmed cell death‐10 enhances proliferation and protects malignant T cells from apoptosis

Lauenborg B, Kopp K, Krejsgaard T, Eriksen KW, Geisler C, Dabelsteen S, Gniadecki R, Zhang Q, Wasik MA, Woetmann A, Odum N. Programmed cell death‐10 enhances proliferation and protects malignant T cells from apoptosis. APMIS 2010; 118: 719–28. The programmed cell death‐10 (PDCD10; also known as cerebral cavernous malformation‐3 or CCM3) gene encodes an evolutionarily conserved protein associated with cell apoptosis. Mutations in PDCD10 result in cerebral cavernous malformations, an important cause of cerebral hemorrhage. PDCD10 is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal‐regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood of cutaneous T‐cell lymphoma (Sezary syndrome) patients. PDCD10 is associated with protein phosphatase‐2A, a regulator of mitogenesis and apoptosis in malignant T cells. Inhibition of oncogenic signal pathways [Jak3, Notch1, and nuclear factor‐κB (NF‐κB)] partly inhibits the constitutive PDCD10 expression, whereas an activator of Jak3 and NF‐κB, interleukin‐2 (IL‐2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10 and cancer.     

Surgery as an Effective Nonpharmacological Mode of Treatment of Atrial Fibrillation Resistant to Standard Therapy

There are two surgical methods for atrial fibrillation (AF) treatment: Maze and corridoring procedures. The first one prevents AF occurrence by performing multiple atriotomies. During the second procedure a corridor between a sino-atrial and the AV node is created together with an electrical isolation of the atria. During 1992 and 1993 seven patients, aged 27–55, mean 43-years-old, with recurrent, resistant to standard therapy AF were referred for surgical treatment to our department. Additional diagnoses include: concealed WPW syndrome in 1 patient, atrial septal defect (ASD) in 3 patients, coronary artery disease in 1 patient. Maze procedure was performed solely in 1 patient, in another together with 2 accessory pathways ablation, in 3 patients with ASD closure and in 1 patient with 2 bypass grafts. In one patient corridoring procedure was performed. Normal sinus rhythm was restored in every patient from 7 to 26 days after the procedure, No surgical complications were noted during the postoperative period. Mechanical function of the atria was documented with echo Doppler 2–6 weeks after the operation. No evidence for AF recurrence was noted within 3–14 months (mean 5 months) of follow-up. The preliminary results of Maze and corridoring procedures are encouraging.     

A Method of Esophageal Electrogram Recording for Diagnostic Atrial and Ventricular Pacing

This study evaluates improvement of the electrogram sensed via an esophageal catheter with the sensing electrode adjacent to the stimulating electrode with and without a specialized artifact suppression system. In 100 patients (65 men and 35 women) aged 16-60 years (mean 48 years), esophageal recordings of left atrial activity were obtained during simultaneous transesophageal atrial pacing. Transesophageal ventricular pacing was performed in an additional 34 patients. Without the suppression system, ventricular paced activity, recorded from the esophagus, was not suitable for interpretation. About 10% of the atrial electrogram response could be recorded and evaluated during atrial pacing. With the stimulus artifact suppression system, interpretable recordings were obtained 100% of the time during atrial and ventricular recordings. The method described allows use of transesophageal diagnostic testing where previously only the intracardiac route was possible.     

On the contribution of prostaglandin-like substances to the action of bradykinin on intestinal motility and blood flow in canine jejunal loop in situ

Blood flow and motility were studied in a canine jejunal loop in situ with intact innervation. Bradykinin was administered into a side branch of the supplying artery and indomethacin was infused intravenously 1 h before experiments. In the control group without indomethacin infusion, bradykinin 1-10 nmol/l gradually increased blood flow without significantly altering motility. Higher concentrations of bradykinin (20-100 nmol/l) augmented rhythmic contractions of the intestine. Phasic blood flow decreased during contraction and increased after relaxation, and mean blood flow increased. Bradykinin (0.2-1.0 mumol/l) caused tonic intestinal contractions. Blood flow initially increased but was soon impeded in proportion to the amplitude and duration of the tonic contractions. With intestinal muscle relaxation, blood flow increased to values markedly higher than control. In the group pretreated with indomethacin, blood flow did not increase after bradykinin administration. However, administration of PGE2 produced significant increase in flow, similar to that observed after bradykinin. Acetylcholine or isoprenaline also markedly increased blood flow. Increased intestinal motility caused by bradykinin mechanically impeded blood flow through the intestine, thus masking its direct vasodilating action. The action of bradykinin on the intestinal vascular bed is probably mediated or modulated by endogenous prostaglandin-like substances.     

Implantable Cardioverter‐Defibrillator in Patients With Hypertrophic Cardiomyopathy: Efficacy and Complications of the Therapy in Long‐Term Follow‐up

ICD in Hypertrophic Cardiomyopathy Patients. Introduction: Although implantable cardioverter‐defibrillators (ICDs) are used in sudden cardiac death (SCD) prevention in high‐risk patients with hypertrophic cardiomyopathy (HCM), long‐term results as well as precise risk stratification are discussed in a limited number of reports. The aim of the study was to assess the incidence of ICD intervention in HCM patients with relation to clinical risk profile. Methods and Results: We studied 104 consecutive patients with HCM implanted in a single center. The mean age of study population was 35.6 (SD, 16.2) years with the average follow‐up of 4.6 (SD, 2.6) years. ICD was implanted for secondary (n = 26) and primary (n = 78) prevention of SCD. In the secondary prevention group, 14 patients (53.8%) experienced at least 1 appropriate device intervention (7.9%/year). In the primary prevention (PP) group appropriate ICD discharges occurred in 13 patients (16.7%) and intervention rate was 4.0%/year. Nonsustained VT was the only predictive risk factor (RF) for an appropriate ICD intervention in the PP (positive predictive value 22%, negative predictive value 96%). No significant difference was observed in the incidence of appropriate ICD discharges between PP patients with 1, 2, or more RF. Complications of the treatment included: inappropriate shocks (33.7%), lead dysfunction (12.5%), and infections: 4.8% of patients. Four patients died during follow‐up. Conclusion: ICD therapy is effective in SCD prevention in patients with HCM, although the complication rate is significant. Nonsustained ventricular tachycardia seems to be the most predictive RF for appropriate device discharges. Number of RF did not impact the incidence of appropriate ICD interventions. (J Cardiovasc Electrophysiol, Vol. 21, pp. 883‐889, August 2010)