Glissonian approach for laparoscopic mesohepatectomy

Experience with advanced techniques has increased the indications for laparoscopic liver resection. This video demonstrates technical aspects of a pure laparoscopic mesohepatectomy using intrahepatic Glissonian technique. To the best of our knowledge, this is the first case of anatomic laparoscopic mesohepatectomy using the Glissonian approach published in the English literature. A 62-year-old man with colorectal liver metastasis occupying central liver segments was referred for surgical treatment. The first step is the control of segment 4 pedicle. Using the round ligament as a guide, one incision is performed on its right margin and another is made at the bottom of segment 4. A vascular clamp is introduced through those incisions to occlude segment 4 Glissonian sheath. The next step is to control the right anterior pedicle. The first incision is made in front of the hilum and another is performed on the right edge of gallbladder bed. Laparoscopic clamp is introduced through these incisions and closed producing ischemic discoloration of segments 5 and 8. Vascular clamp is replaced by an endoscopic vascular stapling device and stapler is fired. Line of liver transection is marked along the liver surface following ischemic area. Liver transection is accomplished with bipolar vessel sealing device and endoscopic stapling device as appropriate. Specimen was extracted through a suprapubic incision. Liver raw surfaces were reviewed for bleeding and bile leaks. Operative time was 200 min with minimum blood loss and no need for blood transfusion. Recovery was uneventful, and the patient was discharged on the fifth postoperative day. Histological examination revealed clear surgical margins. Mesohepatectomy can be safely performed laparoscopically in selected patients and by surgeons with expertise in both liver surgery and laparoscopic techniques. The use of the intrahepatic Glissonian approach may help to identify the exact limits of the mesohepatectomy to avoid ischemic injury of the remnant liver.

Trans-resveratrol inhibits early blood vessel formation (Vasculogenesis) without impairment of embryonic growth

Resveratrol is a stilbene compound found in grapes and other sources. In this study we examined the effects of trans-resveratrol (4.38-438 mu M/implant) in the vasculogenesis of yolk-sac membranes and its capacity to improve chick embryo growth. High concentrations of the stilbene (43.8-438 mu M) significantly inhibited early vessel formation, decreasing the percentage vitelline vessels of 3.5-day embryos by 50% compared to the control. In addition, basic fibroblast growth factor-stimulated vasculogenesis (140% of vessels as compared to control) was partially reversed by t-resveratrol (35% of inhibition) and treatments with cyclooxygenase inhibitors (acetylsalicylic acid and indomethacin) as well a protein-kinase C (PKC) activator (phorbol-12,13-dibutyrate) decreased the vessel number to 60%, 50%, and 44%, respectively. Treatments with t-resveratrol (4.38-43.8 mu M/implant) significantly increased the body length of embryos incubated in vitro uncoupled from any impairment in the body shape or detectable embryotoxic effect. We suggest that the antivasculogenic activity and the enhancement in embryonic growth promoted by non acute treatments with t-resveratrol were, at least in part, due to PKC inhibition. We suggest that t-resveratrol can be usable not only as a reliable functional nutriment, but also is useful for the development of prophylactic and/or therapeutic agents for treatment of angiogenic-degenerative diseases.

Mandibular appliance modulates condylar growth through integrins

Functional orthopedic therapy corrects growth discrepancies between the maxilla and mandible, possibly through postural changes in the musculature and modulation of the mandibular condylar cartilage growth. Using Wistar rats, we tested the hypothesis that chondrocytes respond to forces generated by a mandibular propulsor appliance by changes in gene expression, and that integrins are important mediators in this response. Immunohistochemical analyses demonstrated that the use of the appliance for different periods of time modulated the expression of fibronectin, alpha 5 and alpha v integrin subunits, as well as cell proliferation in the cartilage. In vitro, cyclic distension of condylar cartilage-derived cells increased fibronectin mRNA, as well as Insulinlike Growth Factor-I and II mRNA and cell proliferation. A peptide containing the Arginine-Glycine-Asparagine sequence (RGD), the main cell-binding sequence in fibronectin, blocked almost all these effects, confirming that force itself modulates the growth of the rat condylar cartilage, and that RGD-binding integrins participate in mechanotransduction.

Comparison of renal transplantation outcomes in children with and without bladder dysfunction. A customized approach equals the difference

Purpose: We examined the development of urological abnormalities in a group of pediatric renal transplant recipients. Materials and Methods: We reviewed 211 patients younger than 19 years who underwent 226 renal transplants. Three groups of patients were studied-136 children with end stage renal disease due to a nonurological cause (group 1), 56 children with a urological disorder but with an adequate bladder (group 2a) and 19 children with lower urinary tract dysfunction and/or inadequate bladder drainage (group 2b). A total of 15 children in group 2b underwent bladder augmentation (ureterocystoplasty in 6, enterocystoplasty in 9), 2 underwent continent urinary diversion, 1 underwent autoaugmentation and 1 underwent a Mitrofanoff procedure at the bladder for easier drainage. Kidney transplantation was performed in the classic manner by extraperitoneal access, and whenever possible the ureter was reimplanted using an antireflux procedure. Results: At a mean followup of 75 months 13 children had died, 59 grafts were lost and 15 children had received a second transplant. Two patients in group 2a required a complementary urological procedure to preserve renal function (1 enterocystoplasty, 1 vesicostomy). A total of 12 major surgical complications occurred in 226 kidney transplants (5.3%), with a similar incidence in all groups. The overall graft survival at 5 years was 75%, 74% and 84%, respectively, in groups 1, 2a and 2b. Conclusions: With individualized treatment children with severely inferior lower urinary tract function may undergo renal transplantation with a safe and adequate outcome.

Gasless fetoscopy: A new approach to endoscopic closure of a lumbar skin defect in fetal sheep

Objective: To develop a new endoscopic approach to the correction of a myelomeningocele-like defect in fetal sheep. Methods: The fetuses of 9 pregnant ewes, with an average gestational age of 115 days, were subjected to a 3.0 x 2.0 cm removal of the skin over the lumbar spine, performed through hysterotomy. The uterus was closed, and three 5-mm endoscopic cannulas, without valve mechanisms, were inserted. In the pilot phase (2 animals), we initially worked exclusively in the amniotic fluid space. In the study phase, we partially withdrew the fetus from the amniotic fluid to completely expose its back. By simply allowing air to enter the amniotic cavity (without gas injection), a working space was created using a uterine lift device. The skin around the defect was dissected, and a biosynthetic cellulose material was applied to cover the area. A continuous suture of the skin was performed to completely hide the material. Results: The combined air/fluid space allowed the skin to be successfully closed in 6 out of 7 cases in the study phase. All fetuses were alive at the end of the procedures. Time to complete the endoscopic part of the procedure fell from 3 to 1 h by the end of this series. Premature birth occurred in 2 of the 4 cases allowed to continue with the pregnancy. Conclusion: A new gasless fetoscopic surgery technique was developed as an alternative to current techniques used for fetal endoscopic surgery. Copyright (C) 2008 S. Karger AG, Basel.

Endoscopic Anatomy of the Pterygopalatine Fossa and the Transpterygoid Approach: Development of a Surgical Instruction Model

Introduction: The pterygopalatine fossa (PPF) is a narrow space located between the posterior wall of the antrum and the pterygoid plates. Surgical access to the PPF is difficult because of its protected position and its complex neurovascular anatomy. Endonasal approaches using rod lens endoscopes, however, provide better visualization of this area and are associated with less morbidity than external approaches. Our aim was to develop a simple anatomical model using cadaveric specimens injected with intravascular colored silicone to demonstrate the endoscopic anatomy of the PPF. This model could be used for surgical instruction of the transpterygoid approach. Methods: We dissected six PPF in three cadaveric specimens prepared with intravascular injection of colored material using two different injection techniques. An endoscopic endonasal approach, including a wide nasoantral window and removal of the posterior antrum wall, provided access to the PPF. Results: We produced our best anatomical model injecting colored silicone via the common carotid artery. We found that, using an endoscopic approach, a retrograde dissection of the sphenopalatine artery helped to identify the internal maxillary artery (IMA) and its branches. Neural structures were identified deeper to the vascular elements. Notable anatomical landmarks for the endoscopic surgeon are the vidian nerve and its canal that leads to the petrous portion of the internal carotid artery (ICA), and the foramen rotundum, and V2 that leads to Meckel`s cave in the middle cranial fossa. These two nerves, vidian and V2, are separated by a pyramidal shaped bone and its apex marks the ICA. Conclusion: Our anatomical model provides the means to learn the endoscopic anatomy of the PPF and may be used for the simulation of surgical techniques. An endoscopic endonasal approach provides adequate exposure to all anatomical structures within the PPF. These structures may be used as landmarks to identify and control deeper neurovascular structures. The significance is that an anatomical model facilitates learning the surgical anatomy and the acquisition of surgical skills. A dissection superficial to the vascular structures preserves the neural elements. These nerves and their bony foramina, such as the vidian nerve and V2, are critical anatomical landmarks to identify and control the ICA at the skull base.

Candidate-Gene Approach in Posttraumatic Stress Disorder After Urban Violence: Association Analysis of the Genes Encoding Serotonin Transporter, Dopamine Transporter, and BDNF

Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3`UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3`UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.

Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty

Background: A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective: To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. Subjects and methods: The GHSR coding region was directly sequenced in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults, and in 197 children with normal stature. The pharmacological consequences of GHSR non-synonymous variations were established using in vitro cell-based assays. Results: Five different heterozygous point variations in GHSR were identified (c.-6 G>C, c.251G>T (p.Ser84Ile), c.505G>A (p.Ala169Thr), c.545 T>C (p.Val182Ala), and c.1072G>A (p.Ala358Thr)), all in patients with CDGP. Neither these allelic variants nor any other mutations were found in 694 alleles from controls. Functional studies revealed that two of these variations (p.Ser84Ile and p. Val182Ala) result in a decrease in basal activity that was in part explained by a reduction in cell surface expression. The p.Ser84Ile mutation was also associated with a defect in ghrelin potency. These mutations were identified in two female patients with CDGP (at the age of 13 years, their height SDS were -2.4 and -2.3). Both patients had normal progression of puberty and reached normal adult height (height SDS of -0.7 and -1.4) without treatment. Conclusion: This is the first report of GHSR mutations in patients with CDGP. Our data raise the intriguing possibility that abnormalities in ghrelin receptor function may influence the phenotype of individuals with CDGP.

Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model

OBJECTIVE: Investigate the effects of antenatal steroids and tracheal occlusion on pulmonary expression of vascular endothelial growth factor receptors in rats with nitrofen-induced congenital diaphragmatic hernia. STUDY DESIGN: Fetuses were exposed to nitrofen at embryonic day 9.5. Subgroups received dexamethasone or were operated on for tracheal occlusion, or received combined treatment. Morphologic variables were recorded. To analyze vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, we performed Western blotting and immunohistochemistry. Morphologic variables were analyzed by analysis of variance and immunohistochemistry by Kruskal-Wallis test. RESULTS: Congenital diaphragmatic hernia decreased body weight, total lung weight, and lung-to-body weight ratio. Tracheal occlusion increased total lung weight and lung-to-body weight ratio (P < .05). Fetuses with congenital diaphragmatic hernia had reduced vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, whereas steroids and tracheal occlusion increased their expression. Combined treatment increased expression of receptors, but had no additive effect. CONCLUSION: Vascular endothelial growth factor signaling disruption may be associated with pulmonary hypertension in congenital diaphragmatic hernia. Tracheal occlusion and steroids provide a pathway for restoring expression of vascular endothelial growth factor receptors.

Assessment of the Expression of IR beta, IRS-1, IRS-2 and IGF-IR beta in a Rat Model of Intrauterine Growth Restriction

Objective: To investigate glomerular development and expression of insulin and insulin-like growth factor receptors in an experimental model of intrauterine growth restriction (IUGR). Material and Methods: We studied three groups of Sprague-Dawley fetuses: IUGR - restricted by ligation of the right uterine artery; C-IUGR - left horn controls, and EC - external controls (non-manipulated). Body and organs were weighed, and glomerular number and volume were analyzed. Expression of IR beta, IRS-1, IRS-2 and IGF-IR beta was analyzed in liver, intestine and kidneys by immunoblotting. Results: Organ/body weight ratios were similar. In IUGR, glomerular number and volume were increased compared to C-IUGR and EC (p < 0.001). In the IUGR liver, increases were found in IGF-IR beta compared to C-IUGR and EC; IR beta compared to EC, and IRS-2 compared to C-IUGR. However, decreases in IR beta were noted in IUGR compared to C-IUGR; IRS-1 compared to C-IUGR and EC, and IRS-2 compared to EC. In IUGR intestine, increases were detected in IR beta, IRS-1 and IGF-IR beta compared to C-IUGR and EC. In IUGR kidneys, increases were observed in IR beta and IGF-IR beta compared to C-IUGR and EC, and IRS-1 compared to EC. Decreased IRS-2 in the intestine and kidney were noticed in IUGR compared to C-IUGR and EC. Conclusion: IUGR fetuses had less glomeruli and alterations in insulin receptors, which may be associated with an increased risk of disease occurrence in adulthood. Copyright (C) 2010 S. Karger AG, Basel

Surgical management of glomus jugulare tumors: a proposal for approach selection based on tumor relationships with the facial nerve Clinical article

Object. The goal of this paper is to analyze the extension and relationships of glomus jugulare tumor with the temporal bone and the results of its surgical treatment aiming at preservation of the facial nerve. Based on the tumor extension and its relationships with the facial nerve, new criteria to be used in the selection of different surgical approaches are proposed. Methods. Between December 1997 and December 2007, 34 patients (22 female and 12 male) with glomus jugulare tumors were treated. Their mean age was 48 years. The mean follow-up was 52.5 months. Clinical findings included hearing loss in 88%, swallowing disturbance in 50%, and facial nerve palsy in 41%. Magnetic resonance imaging demonstrated a mass in the jugular foramen in all cases, a mass in the middle ear in 97%, a cervical mass in 85%, and an intradural mass in 41%. The tumor was supplied by the external carotid artery in all cases, the internal carotid artery in 44%, and the vertebral artery in 32%. Preoperative embolization was performed in 15 cases. The approach was tailored to each patient, and 4 types of approaches were designed. The infralabyrinthine retrofacial approach (Type A) was used in 32.5%; infralabyrinthine pre- and retrofacial approach without occlusion of the external acoustic meatus (Type B) in 20.5%; infralabyrinthine pre- and retrofacial approach with occlusion of the external acoustic meatus (Type C) in 41 W. and the infralabyrinthine approach with transposition of the facial nerve and removal of the middle ear structures (Type D) in 6% of the patients. Results. Radical removal was achieved in 91% of the cases and partial removal in 9%. Among 20 patients without preoperative facial nerve dysfunction, the nerve was kept in anatomical position in 19 (95%), and facial nerve function was normal during the immediate postoperative period in 17 (85%). Six patients (17.6%) had a new lower cranial nerve deficit, but recovery of swallowing function was adequate in all cases. Voice disturbance remained in all 6 cases. Cerebrospinal fluid leakage occurred in 6 patients (17.6%), with no need for reoperation in any of them. One patient died in the postoperative period due to pulmonary complications. The global recovery, based on the Karnofsky Performance Scale (KPS), was 100% in 15% of the patients, 90% in 45%, 80% in 33%, and 70% in 6%. Conclusions. Radical removal of glomus jugulare tumor can be achieved without anterior transposition of the facial nerve. The extension of dissection, however, should be tailored to each case based on tumor blood supply, preoperative symptoms, and tumor extension. The operative field provided by the retrofacial infralabyrinthine approach, or the pre- and retrofacial approaches. with or without Closure of the external acoustic meatus, allows a wide exposure of the jugular foramen area. Global functional recovery based on the KPS is acceptable in 94% of the patients. (DOI: 10.3171/2008.10.JNS08612)

Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31-36 and 2 at 17q24-25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.