Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Three dimensional computed tomographic imaging in planning the surgical approach for redo cardiac surgery after coronary revascularization.

OBJECTIVE: Reoperative cardiac surgery after previous coronary artery bypass grafting represents a surgical challenge due to the potential for injury to patent coronary grafts, aorta or right ventricle. Standard preoperative imaging using a coronary angiogram and chest radiograph (CXR) often results in inaccurate assessment of mediastinal anatomy. We aimed to evaluate 3D volume rendered computed tomographic imaging as an adjunct to standard preoperative assessment of patients requiring cardiac surgery in whom coronary artery revascularization had been performed in the past. METHODS: Between January 2003 and January 2004, 33 patients with previous coronary revascularization referred for reoperative cardiac surgery underwent preoperative 3D CT imaging in order to optimize the surgical approach. The mean age in this patient population was 72+/-8 years. The combined evaluation of CXR and conventional angiography offered incomplete insight into pertinent mediastinal topography in 85% of patients (28/33). RESULTS: The correlations for distances of the left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft from the midline and posterior sternum obtained by CT angiography (CTA) and CXR were poor, R=0.56 and 0.49, respectively. The correlation coefficients for distances between the right ventricle and the aorta to the sternum obtained by the same methods were similarly marginal, 0.58 and 0.48, respectively. The correlation coefficients for distances between the LIMA to LAD, circumflex and right coronary artery grafts from the midline obtained by CTA and conventional angiography were 0.54, -0.13 and 0.43, respectively. In seven patients (21%) the surgical strategy was modified based on the location of patent grafts in the mediastinum. The hospital mortality was 17% (5/29). Intraoperative injuries to vital structures were encountered in two patients (7%). No injuries to patent LIMA or the aorta were encountered. CONCLUSIONS: The 3D CT imaging technique is useful in defining the optimal surgical strategy for reoperative cardiac surgery. We found that CTA is superior to CXR and conventional angiography in defining the position of patent grafts and vital structures in relation to the midline and posterior sternum. Preoperative mapping of patent coronary grafts and other vital mediastinal structures reduces the morbidity of the reoperation through modification of surgical approaches.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.      

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L- lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.