Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS: We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION: Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.

Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South American Transplant Center.

BACKGROUND: Around 2.4% of the world's population is infected with hepatitis C virus (HCV), and it is the most common cause of liver transplantation (LT) in the world. Latin America (LA), with nearly 9% of the world population, has had a continuous increase in the number of LTs per year. Yet, due to the lack of mandatory data collection and a well-developed health-care system, access to transplantation is limited in most LA countries. We report the first LA experience of HCV-infected LT patients. METHODS: We performed a retrospective cohort study by reviewing the medical histories of all HCV-infected LT patients between 1996 and 2016 who acquired HCV before their LT, at the Fundación Valle del Lilí, Cali, Colombia. RESULTS: Between January 1996 and December 2015, a total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV infection. With a median follow-up time of 24.4 months (interquartile range [IQR] 4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996-2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in 30.6% of the patients, and overall postoperative complications had an incidence of 80%. CONCLUSIONS: This is the first report of LT in HCV-infected patients in Colombia and in LA. Our results are comparable to those of other transplant centers worldwide with regard to postoperative complications and patient survival. Patients with LT in the 1996-2006 time frame had higher morbidity and mortality. Studies including larger numbers of patients are needed to determine the reason for this finding.

Dynamical analysis for a scalar-tensor model with Gauss-Bonnet and non-minimal couplings.

We study the autonomous system for a scalar-tensor model of dark energy with Gauss-Bonnet and non-minimal couplings. The critical points describe important stable asymptotic scenarios including quintessence, phantom and de Sitter attractor solutions. Two functional forms for the coupling functions and the scalar potential are considered: power-law and exponential functions of the scalar field. For the exponential functions the existence of stable quintessence, phantom or de Sitter solutions, allows for an asymptotic behavior where the effective Newtonian coupling becomes constant. The phantom solutions could be realized without appealing to ghost degrees of freedom. Transient inflationary and radiation-dominated phases can also be described.

Factors associated with infection by Campylobacter fetus in beef herds in the Province of Buenos Aires, Argentina.

Campylobacter fetus is a major venereal pathogen of cattle that is considered to be widespread among the livestock population of Argentina. The disease accounts for a 10% reduction in the weaning rate of Argentine infected herds and annual losses of $165 million. A case-control, questionnaire-based study was developed with the objective of quantifying the association between C. fetus infection and demographic, husbandry, and sanitary factors in 196 herds located in the province of Buenos Aires, Argentina. Abortions observed in the herd (OR=3.08, 95% CI=1.52, 6.23), and trespassing of bulls from neighboring herds (OR=2.03, 95% CI=0.98, 4.20), were positively associated with the risk of finding C. fetus-infected bulls, whereas buying bulls was a protective factor for the disease (OR=0.53, 95% CI=0.26, 1.08). Results presented here will help to develop and implement actions aimed at preventing the spread and reducing the incidence of C. fetus infection in the beef cattle population of Argentina.

Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction.

Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.

Canine intraneural perineurioma.

A 6-year-old castrated German Shepherd Dog was presented with a 6-month history of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots after later amputation revealed distended hypercellular fascicles. This distension was due to widely separated axons surrounded by concentric lamellations formed by neoplastic perineurial cells and their processes. These pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma. The perineurioma cell processes were immunonegative for S-100 (alpha and beta chains) and collagen IV, but were immunoreactive for laminin. The central axons were also immunoreactive for NF-200 and S-100. The proliferative index of the perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%. Ultrastructurally, the widely separated, interdigitating perineurioma cell processes were connected by desmosomal-like junctional complexes to form continuous circles. Their processes were covered by a discontinuous basal lamina. Each centrally placed axon was normally, thinly, or completely unmyelinated and was surrounded by a normal Schwann cell. These morphologic and immunologic features distinguish this lesion from hypertrophic neuropathy and were consistent with intraneural perineurioma.

HIV-1-derived lentiviral vectors and fetal route of administration on transgene biodistribution and expression in rhesus monkeys.

The gene transfer efficiency of lentiviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein (VSV-G) driven by the MND or CMV promoters and expressing the enhanced green fluorescent protein (EGFP) was investigated in fetal rhesus monkeys (Macaca mulatta) (N=21). Fetuses (50+/-10 days gestation; term 165+/-10 days) were injected under ultrasound guidance using an intraperitoneal (i.p.) or intrahepatic (i.h.) approach with a range of 1 x 10(7)-2 x 10(8) infectious particles/fetus. Analysis of transgene biodistribution and expression was performed in multiple tissues at 3-7 months postgene delivery using quantitative techniques. Overall, results indicated the following: (1) i.p. gene transfer at 40 days gestation resulted in a more diffuse distribution of the vector compared to administration at 60 days gestation; (2) vector biodistribution was similar after administration by the i.p. or i.h. routes; and (3) gene expression analysis in transduced tissues showed the presence of mRNA transcripts that correlated with the level of gene transfer. These studies suggest that fetal gene transfer using the i.p. and i.h. routes results in prolonged transduction and expression of the transgene in multiple tissues.

Establishment of normative data for orbital and nasal soft-tissue measurements among Filipino children.

This article establishes the soft-tissue norms among Filipino children from ages birth to 17 years of age. Specific measurements were made at the inner canthal region, the outer canthal region, and the nasal length. This was to help establish normative graphs among this population of children.

Venous air embolism during endoscopic strip craniectomy for repair of craniosynostosis in infants.

BACKGROUND: Various studies have reported an incidence of venous air embolism (VAE) as high as 82.6% during surgical procedures for craniosynostosis. There has been an increase in the use of minimally invasive, endoseopie surgical procedures, including applications for endoscopic strip craniectomy. The current study prospectively evaluated the incidence of VAF during endoscopic strip craniectomy. METHODS: Continuous, intraoperative monitoring for VAE was performed using precordial Doppler monitoring. A recording was made of the Doppler tones and later reviewed to verify its accuracy. RESULTS: The cohort for the study included 50 consecutive neonates and infants ranging in age from 3.5 to 36 weeks and ranging in weight from 3 to 9 kg. Surgical time varied from 31 to 95 min for a total of 2,701 mm of operating time, during which precordial Doppler tones were auscultated. In 46 patients, there was no evidence of VAE. In four patients, there was a single episode of VAE. Two of the episodes of VAE were grade I (change in Doppler tones), and two were grade H (change in Doppler tones and decrease in end-tidal carbon dioxide). No grade III (decrease in systolic blood pressure by 20% from baseline) VAF was noted. CONCLUSION: In addition to previously reported benefits of decreased blood loss, decreased surgical time, and improved postoperative recovery time, the authors noted a low incidence of VAF during endoscopic strip craniectomy in neonates and infants.

Effects of synthetic craniofacial materials on cerebral microcirculation.

Four groups were studied to look at effects of synthetic materials on the pial vasculature. Using Sprague-Dawley rats, an open pial window approach was used in which there was a control group, a hydroxyapatite cement group mixed with sodium phosphate, a methylmethacrylate slow-set, and a methylmethacrylate fast-set group. There were 10 animals with 20 vessels studied within each group. The permeability leakage outside the vessel was evaluated to determine the vascular albumin leakage, and the number of rolling and adherent leukocytes was studied within each group. It was seen that the control group was significantly different compared with the fast-set methylmethacrylate group during a 2-hour period in regard to the percentage leakage, as well as a number of rolling and adherent leukocytes. This is one of the first studies to demonstrate the effects of synthetic craniofacial materials on the underlying pial vasculature.

Primary canine and feline nervous system tumors: intraoperative diagnosis using the smear technique.

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.

Temporalis muscle resuspension using titanium miniplates and screws: technical note.

OBJECTIVE: To describe the technique for and results of using titanium miniplates and screws for resuspension of the temporalis muscle after osseous detachment during cranial procedures requiring exposure of and access to the frontotemporoparietal region. METHODS: Thirty-four patients, who were being treated with various cranial procedures, underwent resuspension of the dissected temporalis muscle, using 1.5-mm or 1.3-mm titanium plates and screws, after bone flap replacement. RESULTS: The temporalis muscle was successfully and securely resuspended in all cases, using the plates and screws. There were no infections, muscle tears, dislodgement, fractures, or temporal hollowing in any of the cases. In four cases that required re-exploration, the muscle was observed to be rigidly fixated and scarred to the bone. CONCLUSION: The use of titanium plates and screws is a safe, simple, successful alternative for reattachment of temporalis muscles for patients undergoing cranial procedures.

In vivo visualization of cerebral microcirculation in systemic thermal injury.

We present a model used to describe the effects of systemic thermal injury in cerebral permeability with the use of an open, acute pial window technique. Sprague-Dawley rats were anesthetized, and an open pial window was constructed. The area was then bathed with artificial cerebrospinal fluid with a pH adjusted to 7.4 that was heated to a constant temperature of 37 degrees C, which was allowed to circulate into a reservoir at a rate of 2 cc/min. The fluid was infused with a gas mixture of 5% carbon dioxide and 95% nitrogen. A warming blanket was placed under the animal's ventral surface, and the animal's temperature was maintained at 37 degrees C and monitored with a rectal thermal probe. Experimental animals were submerged to the xiphoid process in 100 degrees C water bath for a total of 6 seconds, which produced a 70% total body surface area third degree burn. Control animals were submerged in 37 degrees C water for 6 seconds. The animals were then injected with a constant infusion of bovine albumin coupled with fluorescein isothiocyanate. Recordings were taken every 15 minutes for 6 hours. The vascular albumin leakage was determined from the ratio of interstitium to vascular fluorescence and expressed as a percentage. The percent albumin leakage in the control group was found to be significantly different from that in the experimental group at all periods measured. The mean increase in permeability ranged from 20% at 15 minutes to 104% at 6 hours. These changes were found to be statistically significant with the use of unpaired t test at a P value of .0001. The model presented is the first to demonstrate changes in cerebral permeability after acute severe systemic thermal injury.

Endoscopy-assisted wide-vertex craniectomy, "barrel-stave" osteotomies, and postoperative helmet molding therapy in the early management of sagittal suture craniosynostosis.

OBJECT: The purpose of this study was to assess the efficacy, safety, associated complications, and outcome in patients with sagittal suture craniosynostosis in whom endoscopy-assisted wide-vertex craniotomy and "barrel-stave" osteotomy were performed. METHODS: During a 4-year period, 59 patients with sagittal suture synostosis underwent endoscopy-assisted wide-vertex craniectomies, barrel stave-like osteotomies, and postoperatively were fitted with custom-made molding helmets. Data on operative time, blood loss, transfusion rates, hospital length of stay, complications, and hospital charges were collected prospectively. The mean patient age at the time of surgery was 3.7 months. The average blood loss was 31.8 ml; and only one patient required an intraoperative blood transfusion. Nine patients received transfusions of donor blood postoperatively. The mean operative time was 50 minutes, and all but three patients were discharged from the hospital the morning following surgery. There were no intraoperative complications. Normocephaly as well as normal cephalic indices were observed at latest follow up. CONCLUSIONS: The authors conclude that early treatment of infants with sagittal suture craniosynostosis by using minimally invasive, endoscopy-assisted wide-vertex craniectomies provides excellent results and a significantly lower morbidity rate than traditional calvarial vault reconstructive procedures.

BoneSource solidification: a comparison between water and sodium phosphate as the solvent.

The purpose of this study was to determine the solidification rates for BoneSource (hydroxyapatite cement) mixed with sterile water versus BoneSource mixed with 0.25 ml of sodium phosphate. The average time for cure for BoneSource mixed with sterile water was 99 minutes, with a SD of 5.3 minutes. The average time for cure for BoneSource and sodium phosphate was 43 minutes, with a SD of 3.6 minutes (P < 0.0003). The average temperature for BoneSource in sterile water was 19.1 degrees C with a SD of 0.082, and the average temperature of BoneSource in sodium phosphate was 20.1 degrees C, with a SD of 0.1. Therefore, sodium phosphate shows that there is a significantly decreased amount of time required to solidify BoneSource and it remains isothermic throughout this reaction.

Propofol for sedation and control of intracranial pressure in children.

Following central nervous system insults, control of intracranial pressure may lessen the incidence of morbidity and mortality. Therapies to control intracranial pressure include osmolar agents, prevention of and control of seizures, drainage of cerebrospinal fluid, hypothermia, and barbiturates. Control of agitation and excessive patient movement are additional components in the management of ICP. Although opioids and benzodiazepines are generally effective, in a small subset of patients, alternative agents may be necessary. The authors present 2 children with increased ICP in whom propofol was used to provide sedation and control ICP. The use of propofol in this setting and its possible applications in the children with increased ICP are discussed.

Endoscopic craniectomy for early correction of craniosynostosis.

Twelve patients between 0.4 and 7.8 months of age were treated by an endoscopic approach to strip craniectomy. Nine patients had sagittal suture involvement. Two patients had a single unilateral lambdoid suture synostosis, and one patient had a combination of a right coronal synostosis and a metopic synostosis. Postoperatively, all patients were placed in cranial remodeling helmets and the results showed that the estimated blood loss ranged from 5 cc to 150 cc, with blood transfusion required in only one patient. All patients were discharged from the hospital by day 2, and all patients had an improvement in their cranial head shape. The specific technique of using the endoscope to aid in performing a strip craniectomy will be discussed. Nine endoscopically treated patients with the diagnosis of sagittal suture synostosis were compared with nine patients treated by using the Marchac remodeling techniques. The mean operative time (1.6 hours versus 3.5 hours), estimated blood loss (43 cc versus 168 cc), hospital costs ($11,671 versus $36,685), and length of stay (1.16 days versus 5.1 days) were less by using the endoscopic technique. All nine patients treated by using the Marchac technique required a blood transfusion, whereas only one patient was transfused in the endoscopically treated group.

Socioeconomic issues and education of neurologic surgery residents in the United States.

BACKGROUND: The goals of this project were to ascertain the extent to which socioeconomic issues are being formally addressed within neurologic training programs in the United States and to determine the perception of chief neurosurgery residents and program directors regarding training and preparation as it relates to these issues. METHODS: The chief neurosurgery residents and program directors for the 1995 academic year were identified and mailed a survey with questions regarding the formal training of socioeconomic issues within their programs. RESULTS: Residents indicated that 95% did not believe their residency program provided adequate training in socioeconomic issues; 97% and 95% respectively, did not feel adequately prepared to deal with the business aspects of a medical practice or to deal with insurance companies and the managed care environment; and 87% did not think they were adequately prepared to deal with a lawsuit. Moreover, from 25%-87% did not know the meaning of terms such as capitation, RVUs, PPOs, or IPAs. The program directors indicated that 58% of the programs did not formally deal with socioeconomic issues. CONCLUSIONS: This survey indicates that socioeconomic issues are not currently being properly addressed in a large proportion of neurosurgical residency programs. An overwhelming majority of the residents did not feel they are adequately prepared to deal with those nonmedical-surgical aspects of the practice of neurosurgery. This perception was corroborated by the response of the program directors. There appears to be a significant deficiency in the training of neurosurgical residents with regard to socioeconomic issues in the United States.