Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene

The difficulty of fine localizing the polymorphisms responsible for genotype-phenotype correlations is emerging as an important constraint in the implementation and interpretation of genetic association studies, and calls for the definition of protocols for the follow-up of associated variants. One recent example is the 3435C>T polymorphism in the multidrug transporter gene ABCB1, associated with protein expression and activity, and with several clinical conditions. Available data suggest that 3435C>T may not directly cause altered transport activity, but may be associated with one or more causal variants in the poorly characterized stretch of linkage disequilibrium (LD) surrounding it. Here we describe a strategy for the follow-up of reported associations, including a Bayesian formalization of the associated interval concept previously described by Goldstein. We focus on the region of high LD around 3435C>T to compile an exhaustive list of variants by (1) using a relatively coarse set of marker typings to assess the pattern of LD, and (2) resequencing derived and ancestral chromosomes at 3435C>T through the associated interval. We identified three intronic sites that are strongly associated with the 3435C>T polymorphism. One of them is associated with multidrug resistance in patients with epilepsy (chi2 = 3.78, P = 0.052), and sits within a stretch of significant evolutionary conservation. We argue that these variants represent additional candidates for influencing multidrug resistance due to P-glycoprotein activity, with the IVS 26+80 T>C being the best candidate among the three intronic sites. Finally, we describe a set of six haplotype tagging single-nucleotide polymorphisms that represent common ABCB1 variation surrounding 3435C>T in Europeans.     

Striatonigral suppression of focal hippocampal epilepsy

Both caudate nucleus (CN) and substantia nigra (SN) appear to be involved in the control of epileptogenic events. Previous investigations had demonstrated that both CN and SN stimulations are able to induce hippocampal theta (theta) rhythm and an inhibition of epileptiform spikes. Since the two structures are reciprocally linked by fibre pathways, experiments were carried out to test the possibility that CN influences the hippocampus via SN or vice versa. To this end, changes in penicillin-induced hippocampal spikes by CN or SN stimulation were studied before and after destruction of SN and CN respectively. Steady interictal activity was induced in the hippocampus of encéphale isolé cats by local injection of penicillin. Stimulations of both CN and SN induced statistically significant reduction of hippocampal spike frequency, and in some cases a clear and regular theta-rhythm. These effects were unchanged by the destruction of either CN or SN. The results add further information to the role played by the basal ganglia and SN in the control of epilepsy, and underline the possibility that caudate and nigral influences on the hippocampus are mediated by different pathways.     

The shell technique: bilateral fronto-orbital reshaping in trigonocephaly

The shell technique, used in the Pediatric Neurosurgical Department at the Catholic University, Rome, since the 1990s for the correction of trigonocephaly, is associated to a significant reduction in surgical time and intraoperative blood loss as compared to other procedures, while allowing an adequate remodelling of the bifrontal bone by means of multiple radial osteotomies. The technique does not necessitate the creation of a supraorbital bar, as the supraorbital ridges are modified in situ, further reducing the operative blood loss. In spite of reduced surgical time and manipulation, this procedure ensures aesthetic and functional results comparable to more extensive and complex cranial vault reshaping procedures. The main limitation of this technique is related to the surgical timing, as better results are obtained between 3 and 9 months of age, when the skull bone is still ductile to work with, thus allowing it to be remodelled by greenstick fractures. Moreover, in this age group, the cranial defects that result from the enlargement of the frontal bone flap by means of radial cuts and from the anterior displacement of its lateral portions may benefit from the more effective bone regeneration which characterizes younger children as compared to their older counterparts. A small number of cases showing either persistent hypotelorism or temporal depression have been observed in the post-operative period, although these residual deformities probably depend on a more extensive involvement of the cranial base in the synostotic process in these patients than on the procedure itself.     

Antibacterial‐nanocomposite bone filler based on silver nanoparticles and polysaccharides

Injectable bone fillers represent an attractive strategy for the treatment of bone defects. These injectable materials should be biocompatible, capable of supporting cell growth and possibly able to exert antibacterial effects. In this work, nanocomposite microbeads based on alginate, chitlac, hydroxyapatite and silver nanoparticles were prepared and characterized. The dried microbeads displayed a rapid swelling in contact with simulated body fluid and maintained their integrity for more than 30 days. The evaluation of silver leakage from the microbeads showed that the antibacterial metal is slowly released in saline solution, with less than 6% of silver released after 1 week. Antibacterial tests proved that the microbeads displayed bactericidal effects toward Staphylococcus aureus, Pseudomonas aeruginosa and Staphylococcus epidermidis, and were also able to damage pre‐formed bacterial biofilms. On the other hand, the microbeads did not exert any cytotoxic effect towards osteoblast‐like cells. After characterization of the microbeads bioactivity, a possible means to embed them in a fluid medium was explored in order to obtain an injectable paste. Upon suspension of the particles in alginate solution or alginate/hyaluronic acid mixtures, a homogenous and time‐stable paste was obtained. Mechanical tests enabled to quantify the extrusion forces from surgical syringes, pointing out the proper injectability of the material. This novel antibacterial bone filler appears as a promising material for the treatment of bone defects, in particular when possible infections could compromise the bone‐healing process. Copyright © 2016 John Wiley & Sons, Ltd.     

Elevation of Carbohydrate Antigen 19.9 in Benign Hepatobiliary Conditions and Its Correlation with Serum Bilirubin Concentration

Background Carbohydrate antigen 19.9 (CA19.9), a tumor marker for malignancies of the hepatobiliary tract and pancreas, has frequently been shown to be deranged in a number of non-malignant conditions that are associated with jaundice. This study aims to demonstrate the correlation between CA19.9 and serum bilirubin concentration in patients with benign conditions and to determine the frequency of a false-positive increase in CA19.9 in patients being investigated for potential HPB malignancies. Methods This is a retrospective review of 83 consecutive patients presenting with an abnormal CA19.9 and radiological or clinical features suggestive of HPB malignancy subsequently shown to have benign disease. All patients were thoroughly investigated and followed up until the diagnosis of malignancy could be safely excluded. Results Serum bilirubin, sodium, lymphocyte count, neutrophil:lymphocyte ratio (NLR), β-human chorionic gonadotrophin (HCG), and age were found to correlate with CA19.9 by Pearson’s correlation (P = 0.001, P = 0.006, P = 0.006, P < 0.001, P = 0.012, and P = 0.049, respectively). In multivariate regression analysis, bilirubin was identified as an independent variable that may predict CA19.9 level (P = 0.028). Conclusion CA19.9 level is significantly influenced by serum bilirubin and elevated levels have been observed in patients with non-malignant HPB conditions. Adjusting CA19.9 according to bilirubin levels is likely to improve the specificity of this antigen in the differential diagnosis of benign and malignant HPB diseases and its reliability in the monitoring of disease response to chemotherapy.