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.     

Spinal metastases treated with bipolar radiofrequency ablation with increased (> 70 °C) target temperature: Pain management and local tumor control

PurposeTo investigate the safety and clinical efficacy of bipolar radiofrequency ablation (b-RFA) with increased (> 70 °C) target temperature for the treatment of spine metastases with the intent of achieving pain relief or local tumor control.Materials and methodsThirty-one patients with a total of 37 metastases who were treated with b-RFA with increased temperature and vertebroplasty from January 2016 to May 2019 were retrospectively included. There were 20 women and 11 men with a mean age of 62.4 ± 10.5 (SD) years (range: 40–78 years). Patients and metastases characteristics, procedure details and clinical outcomes were analyzed.ResultsMetastases were predominantly located in lumbar (22/37; 59.5%) or thoracic spine (13/37; 35.1%). Mean target temperature was 88.4 ± 3.5 (SD) °C (range: 70–90 °C). Technical success was 100% (37/37 metastases). One (1/37; 2.7%) major complication unrelated to b-RFA was reported. One (1/37; 2.7%) metastasis was lost to follow-up. Favorable outcome was noted in patients receiving b-RFA for pain management (16/20 metastases; 80%; mean follow-up, 3.4 ± 2.9 [SD] months) or with oligometastatic/oligoprogressive disease (6/6 metastases; 100%; mean follow-up, 5.0 ± 4.6 [SD] months). In patients receiving b-RFA to prevent complications, favorable outcome was noted in 6/10 metastases (60%; mean follow-up, 3.8 ± 4.8 [SD] months).ConclusionsB-RFA with increased target temperature has an excellent safety profile and results in high rates of pain relief and local metastasis control in patients with oligometastatic/oligoprogressive disease. Suboptimal results are achieved in patients receiving b-RFA to prevent complications related to the growth of the index tumor.     

Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study

BACKGROUND: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. METHODS: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. RESULTS: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=-0. 739, P<0.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=-0.90, P<0.0001). CONCLUSIONS: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.     

Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2 mm from both applicators tips, the maximum temperature increase is approximately 60 °C downward from the tips, while it increases of about 40 °C and 30 °C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91?±?0.09 vs. 0.95 cm³). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue.     

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.     

Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients

BACKGROUND: Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer. OBJECTIVES: To investigate the demographic, clinical, serologic features, and survival in a large series of MC patients. METHODS: The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover, the prognostic relevance of the main variables was investigated by Cox model analysis. RESULTS: In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody, 92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively benign clinical course in over 50% of cases, whereas a moderate-severe clinical course was observed in one third of patients whose prognosis was severely affected by renal and/or liver failure. In a limited, but significant, percentage (15%) of individuals, the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier method revealed a significantly lower cumulative 10th-year survival, calculated from time of diagnosis, in MC patients compared with expected death in the age- and sex-matched general population. Moreover, significantly lower survival rates were observed in males and in subjects with renal involvement. The multivariate analysis by the Cox proportional hazard regression model further supported the above findings: an increased mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978) and of 197% in patients with, compared with those without, renal involvement (hazard ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of 97 patients, the causes of death were ascertained: nephropathy (33%), malignancies (23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent causes of death. CONCLUSIONS: Careful patient monitoring is recommended for a timely diagnosis of life-threatening MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or other malignancies.     

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.