Ferenc Rárosi

The effects of laparoscopic Nissen fundoplication on Barrett's esophagus: Long-term results

Abstract Objective. The aim of our study was to conduct a retrospective investigation of the efficacy of laparoscopic Nissen fundoplication in patients with Barretts esophagus. Material and methods. A total of 78 patients with Barretts esophagus underwent surgery. Patients were divided into three groups on the basis of the preoperative endoscopic biopsies: a non-intestinal group (n = 63) with fundic or cardiac metaplasia, an intestinal group (n = 18) with intestinal metaplasia, and a dysplastic group (n = 7) with low-grade dysplasia. Clinical follow-up was available in the case of 64 patients at a mean of 42 ± 16.9 months after surgery. Results. Check-up examination revealed total regression of Barretts metaplasia in 10 patients. Partial regression was seen in 9 cases, no further progression in 34 patients, and progression into cardiac or intestinal metaplasia in 11 patients. No cases of dysplastic or malignant transformation were registered. Where we observed the regression of BE, among the postoperative functional examinations results of manometry (pressure of lower esophageal sphincter) and pH-metry were significantly better compared with those groups where no changes occurred in BE, or progression of BE was found. Discussion. Our results highlight the importance of the cases of fundic and cardiac metaplasia, which can also transform into intestinal metaplasia. Conclusions. Antireflux surgery can appropriately control the reflux disease in a majority of the patients who had unsuccessful medical treatment, and it may inhibit the progression and induce the regression of Barretts metaplasia in a significant proportion of these patients.

Individualized positioning for maximum heart protection during breast irradiation

Abstract Background. Prone positioning has been found feasible and appropriate for the reduction of radiation exposure of the lungs, but its effects on the heart dose remain controversial. Individual anatomical features were sought for the selection of optimal treatment positioning. Material and methods. In 138 left-sided breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were generated in both prone and supine positions. Results. The radiation doses to the left anterior descending coronary artery (LAD) and heart in the two positions differed individually, and were strongly related to the body mass index (BMI). Image fusion of the CT scans revealed that prone positioning was detrimental if the heart was situated distant from the chest wall in the supine position, but moved to the chest wall in the prone position. For characterization of the geography of the heart and the breast, the median distance between the LAD and the chest wall (dmedian), and the heart area included in the radiation field on a single CT scan at the middle of the heart in the supine position (Aheart) proved most appropriate. Conclusion. A validated statistical model, utilizing the BMI, dmedian and Aheart, permits individualized positioning for maximum heart protection.

Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation

Predicting lethal arrhythmia liability from beat‐to‐beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia‐free ECGs for this. Recently, it was shown that drug‐induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia‐induced ventricular fibrillation (VF).

Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia

Cytarabine (cytosine arabinoside, ara‐C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara‐C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside‐drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara‐C are associated with toxicity and clinical outcome in a patient population with childhood ALL.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts

INTRODUCTION Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. METHODS Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. RESULTS Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. DISCUSSION IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening.

Spectrum of neurodevelopmental disabilities: A cohort study in hungary

The spectrum of neurodevelopmental disabilities was studied in a cohort of patients in Hungary. A search for etiologies and assessment of the degree of intellectual disability were carried out. The study included 241 (131 boys) patients. Disability occurred without any prenatal, perinatal, and/or neonatal adverse events in 167 patients. They were classified into the following subgroups: genetic syndromes with recognized etiology, global developmental delay/intellectual disability in association with dysmorphic features but unknown etiology, global developmental delay/intellectual disability without dysmorphic features and recognized etiology, brain malformations, inborn errors of metabolism, leukoencephalopathies, epileptic syndromes, developmental language impairment, and neuromuscular disorders. Adverse events occurred in 74 children classified into subgroups such as cerebral palsy after delivery preterm or at term, and disabilities without cerebral palsy. The etiology was identified in 66.4%, and genetic diagnosis was found in 19.5%. Classification of neurodevelopmental disorders contribute to etiological diagnosis, proper rehabilitation, and genetic counseling.

Does it really matter how far from the fundus embryos are transferred

OBJECTIVE Embryo transfer (ET) is an important last step during the process of IVF. Over the years much has been learned about the importance of the details of this procedure including the potential impact of transfer depth on outcome. The objective of our study was to evaluate whether transfer depth assessed by air bubble location after ET is associated with clinical outcome. STUDY DESIGN Retrospective analysis of the association between transfer distance from the fundus (assessed by air bubble location after ET) and IVF outcome based on cycles (N=409) of patients with good prognosis undergoing infertility treatment for various indications. Treatments followed standard stimulation, IVF-ICSI and ET procedures. The distance of the air bubble as a surrogate marker of embryo location after transfer was measured and was correlated with implantation (IR) and pregnancy rates (PR) after day 3 and day 5 ET. Univariate comparisons were performed by nonparametric methods and multiple logistic regression was used to further evaluate the association between pregnancy rate and those factors that might influence outcome. RESULTS The distance of the bubble was similar in those cycles that led to a pregnancy and those that did not (6.7 vs 6.5mm; p=0.48) and PR were comparable when the transfer was in the upper or middle third of the cavity. The IR did not differ when embryos were transferred into the upper, middle or lower third of the uterine cavity. Outcome was analyzed separately based on the day of transfer (cleavage vs blastocyst stage) and the IR did not differ based on the location of the transfer. CONCLUSIONS Transfer depth does not affect implantation and pregnancy rates when the ET is in the middle or upper third of the uterus.

Aortic arch and common carotid artery plaques with soft components pose a substantial risk of cerebral embolization during carotid stenting

Objectives A higher rate of embolization is considered a disadvantage of carotid stenting (CAS), when compared with carotid endarterectomy. Plaques in the aortic arch (AA) and the common carotid artery (CCA) may be additional sources of embolization to stented internal carotid plaques during CAS. In this study, we aimed to investigate the relationship between these plaques and intracerebral embolization. Methods We analyzed the occurrence and composition of plaques in the AA and CCA by computed tomography angiography (CTA) in 101 consecutive cases of CAS. Cases of peri-procedural embolization were detected on diffusion-weighted imaging as lesions demonstrating diffusion restriction. We applied the χ2 and Fisher’s exact tests, as well as logistic regression models. Results The occurrence of plaques in the AA and CCA was significantly related to the appearance of new diffusion-weighted imaging lesions (p = 0.013 and p = 0.004, respectively). Patients with soft plaques in the AA or CCA had a significantly higher risk of embolization than those without plaques (p = 0.012 and p = 0.006, respectively). In contrast, homogeneously calcified plaques did not pose significantly higher risks. Conclusions Soft plaques in the AA and CCA result in a substantial risk of embolization during CAS. Use of a CTA examination of the AA and the CCA in patients with carotid stenosis may help to select lower-risk patients for CAS.

Novel Insight Into the Role of CFTR in Lacrimal Gland Duct Function in Mice

Purpose The role of cystic fibrosis transmembrane conductance regulator (CFTR) in lacrimal gland (LG) function has only recently received some attention, mainly from our group. In the present study, we investigated the potential changes of LG pathology, tear secretion, ocular surface integrity, and fluid secretion in isolated LG ducts from CFTR knockout (KO) mice. Methods Tear production and ocular surface integrity were investigated in anesthetized wild-type (WT) and KO mice using cotton threads and fluorescein staining, respectively. Immunofluorescence was used to localize CFTR protein in the LGs. Ductal fluid secretions evoked by forskolin (10 μM); cell-permeable cAMP analogue (8-bromo cAMP, 100 μM); or carbachol (100 μM) were measured in isolated LG ducts using video-microscopy. Intracellular Ca2+ homeostasis underlying carbachol stimulation was investigated with microfluorometry. Results Significant decrease in tear secretion and impaired ocular surface integrity were observed in KO mice. Immunofluorescence demonstrated the predominant presence of CFTR protein in the apical membranes of the duct cells from WT mice. Continuous fluid secretion was evoked by forskolin and 8-bromo cAMP in LG ducts from WT mice, while no secretory response was observed in ducts from KO mice. Carbachol caused similar secretory responses in ducts from WT and KO animals without significant differences in cytosolic Ca2+ signaling. Conclusions Our results suggest the important role of CFTR in LG ductal secretion and in the maintenance of ocular surface integrity, suggesting that CFTR may be a promising target of novel therapeutic approaches in the treatment of dry eye.

Abstract P1-10-11: Prone vs. supine positioning for optimizing radiation heart exposure during left breast radiotherapy: A simple clinical tool for prediction*

The benefit of reduced radiation heart exposure in the prone vs. supine position, individually differs according to the anatomical features of the patient (Varga Z, Int J Radiat Oncol Biol Phys. 2009;75:94-110). Preferable positioning may be predicted by a statistical model. This validated calculator using the patient9s body mass index (BMI), the median distance of the anterior surface of the left coronary artery (LAD) from the chest wall (Dmed) and the heart area (Aheart) included in the radiation field in a single CT scan at the middle of the heart (median plane, Pmed) provides quantitative estimates of the dose differences to the LAD or heart in the two positions (Varga Z, Acta Oncol. 2014;53:58-64). In this prospective cohort study, the goal was to develop a reliable method to collect data for the calculator without acquiring a full series of CT scans in both positions. The study was approved by the Institutional Review Board of the University of Szeged, and all the enrolled patients gave their written informed consent to participation. Eligible patients needed postoperative left breast radiotherapy. In 100 patients, a single CT slice image representing the middle of the heart (reference plane, Pref) was acquired by using the AP scout view in the supine position for the selection of the transversal plane appropriate for the measurements of Dmed and Aheart. Thereafter, CT series were acquired in both positions, and analyses were performed on 1. the conformance of the Pref with Pmed , 2. the effect of plane miss on the choice of preferable position. 3. Finally the sensitivity and specificity of this simple clinical method was reevaluated based on the dosimetry data (mean LAD dose, V25Gy heart) obtained using the topogram for selecting the position. In 55 cases, Pref was the same as Pmed, while in 27 and 18 cases, Pref and Pmed differed by 2 or more planes, respectively. No difference was found between the values of Dmed or Aheart asmeasured in Prefvs.Pmed, independently whether Pref was identified correctly or not.The suggestion on treatment position per Pref measurements, was correct in 85 cases, was ambiguous in 8 cases and incorrect in 7 cases. Sensitivity of the calculator based on Pref measurements was 90% (both mean LAD dose and V25Gy heart), while specificity was 72% (mean LAD dose) and 68% (V25Gy heart). The simple clinical method was tested in additional 60 left breast radiotherapy cases, by taking a topogram and a CT series in the suggested position only. Mean LAD dose (mean [CI95%] prone vs. supine: 6.5 [5.7-7.3] Gy vs. 7.5 [5.6-9.5] Gy) and V25Gy heart (mean [CI95%] prone vs. supine: 0.87 [0.67-1.11] % vs. 1.13 [0.55-1.71]%) well corresponded to the institutional dose constraints based on dosimetry data achieved with individual positioning in >300 patients with left-sided breast cancer. We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiation. *Supported by the VKSZ 12-1-2013-0012 project. Citation Format: Kahan Z, Gaal S, Cserhati A, Rarosi F, Boda K, Varga Z. Prone vs. supine positioning for optimizing radiation heart exposure during left breast radiotherapy: A simple clinical tool for prediction* [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-11.