Conversion of Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass Results in Restoration of the Positive Effect on Weight Loss and Co-morbidities: Evaluation of 101 Patients

BACKGROUND: Vertical banded gastroplasty (VBG) is a widely used restrictive procedure in bariatric surgery. However, the re-operation rate after this operation is high. In the case of VBG failure, a conversion to Roux-en-Y gastric bypass (RYGBP) is an option. A study was undertaken to evaluate the results of the conversion from VBG to RYGBP. METHODS: 101 patients had conversion from VBG to RYGBP. Patients were separated into 3 groups, based on the indication for conversion: weight regain (group 1), excessive weight loss (group 2) and severe eating difficulties (group 3). Data for the study were collected by retrospective analysis of prospectively recorded data. RESULTS: Weight regain (group 1) was the reason for conversion in 73.3% of patients. Staple-line disruption was the most important cause for the weight regain (74.3%). Excessive weight loss (group 2) affected 14% of patients and was caused by outlet stenosis in 78.6% of patients. The remaining 13% had severe eating difficulties as a result of outlet stenosis (46.1%), pouch dilatation (30.8%) and pouch diverticula (23.1%). Mean BMI before conversion to RYGBP was 40.5, 22.3 and 29.8 kg/m2 in group 1, 2 and 3, respectively. Minor or major direct postoperative complications were observed in 2.0% to 7.0%. Long-term complications were more frequent, and consisted mainly of anastomotic stenosis (22.7%) and incisional hernia (16.8%). Follow-up after conversion was achieved in all patients (100%), with a mean period of 38 +/- 29 months. BMI decreased from 40.5 to 30.1 kg/m2, increased from 22.3 to 25.3 kg/m2. and decreased slightly from 29.8 to 29.0 kg/m2 in group 1, 2 and 3, respectively. All patients in group 3 noticed an improvement in eating difficulties. CONCLUSION: Complications after conversion from failed VBG to RYGBP are substantial and need to be considered. However, the conversion itself is a successful operation in terms of effect on body weight and treating eating difficulties after VBG

Liver cell therapy: is this the end of the beginning?

The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

NFkappaB prevents apoptosis and liver dysfunction during liver regeneration.

Although NFkappaB binding activity is induced during liver regeneration after partial hepatectomy, the physiological consequence of this induction is unknown. We have assessed the role of NFkappaB during liver regeneration by delivering to the liver a superrepressor of NFkappaB activity using an adenoviral vector expressing a mutated form of IkappaBalpha. This adenovirus (Ad5IkappaB) was almost exclusively expressed in the liver and inhibited NFkappaB DNA binding activity and transcriptional activity in cultured cells as well as in the liver in vivo. After partial hepatectomy, infection with Ad5IkappaB, but not a control adenovirus (Ad5LacZ), resulted in the induction of massive apoptosis and hepatocytes as demonstrated by histological staining and TUNEL analysis. In addition, infection with Ad5IkappaB but not Ad5LacZ decreased the mitotic index after partial hepatectomy. These two phenomena, increased apoptosis and failure to progress through the cell cycle, were associated with liver dysfunction in animals infected with the Ad5IkappaB but not Ad5LacZ, as demonstrated by elevated serum bilirubin and ammonia levels. Thus, the induction of NFkappaB during liver regeneration after partial hepatectomy appears to be a required event to prevent apoptosis and to allow for normal cell cycle progression