Intra-abdominal inverted umblical cord in gastroschisis: a unique ultrasound finding.

A relatively new surgical technique allows for sutureless closure of a gastroschisis defect. Immediately after birth, a long umbilical cord stump is temporarily inverted into the abdominal cavity and later retracted and used to close the abdominal wall defect. Knowledge of this entity is important since the inverted umbilical cord simulates an intra-abdominal mass on cross-sectional imaging. While this procedure is well described in the surgical literature, the imaging features of inverted umbilical cord have yet to be reported. The case presented here highlights the sonographic imaging findings of the umbilical cord during the intestinal decompression phase of sutureless repair of gastroschisis.

Development of anaplastic Wilms tumor and subsequent relapse in a child with diaphanospondylodysostosis.

Diaphanospondylodysostosis (DSD) is a rare skeletal dysplasia syndrome resulting from disordered mesenchymal differentiation. Children with DSD generally die in utero or during the first month of life from severe thoracic insufficiency syndrome. An association of DSD with nephroblastomatosis has been observed, but the natural history of such nephroblastomatosis remains poorly characterized due to the rarity of the underlying condition. We describe a patient with DSD who developed bilateral hyperplastic nephroblastomatosis that ultimately evolved into therapy-resistant anaplastic Wilms tumor (nephroblastoma).

Prenatal presentation and outcome of children with pleuropulmonary blastoma.

BACKGROUND/PURPOSE: Pleuropulmonary blastoma (PPB) is a rare primary neoplasm of pleuropulmonary mesenchyme. Fewer than 170 children have been reported, and few single institutions have reported more than several cases. Treatment for this condition is primarily surgical resection; however, increasing experience suggests that adjuvant chemotherapy may decrease recurrence and improve outcome. METHODS: We reviewed the charts of all children with PPB treated at our institution since 1960. We reviewed the prenatal features, clinical presentation, operation, pathological findings, adjuvant treatment, and outcome. RESULTS: Ten children (6 boys and 4 girls) were treated for PPB at a mean age of 3.2 +/- 4.3 years. In 2, a cystic lung mass was diagnosed prenatally, and in 8, a cystic or solid and cystic lung mass was diagnosed postnatally (right lung, 3; left lung, 4; and bilateral, 3). In no patient was PPB considered preoperatively. Surgical resection was performed at 1 day to 11 years (median, 23 months) of age. Seven children had complete resection; 1 had microscopic residual disease, and 2 had gross residual disease. Pathology showed type I PPB in 7, type II in 1, and type III in 2. Five patients received adjuvant chemotherapy with vincristine, actinomycin, and cyclophosphamide-based regimens. At follow-up (mean, 7.7 +/- 11.5 years; range, 1-456 months), children with type I PPB have no evidence of disease (n = 6) or are lost to follow-up (n = 1), whereas all those with type II/III PPB have died of the disease. CONCLUSIONS: PPB must be included in the differential diagnosis of a fetus, neonate, or child with a cystic lung mass. This finding supports early resection of these lesions rather than observation or treatment with nonoperative strategies.

Laparoscopic obturator hernia repair in an adolescent.

Obturator hernia is rare and has not been described in the pediatric population. The authors describe a case in a 12-year-old girl who presented with nonspecific abdominal pain and who was treated with a laparoscopic primary hernia repair.

Portal vein thrombosis after laparoscopic splenectomy: an ongoing clinical challenge.

OBJECTIVES: Portal vein thrombosis (PVT) following open splenectomy is a potentially lethal complication with an incidence of up to 6%. The objective of this report is to describe our management of a recent laparoscopic case, discuss current therapies, and consider antiplatelet therapy for prophylaxis. METHODS: Medical records, laboratory studies, and imaging studies pertaining to a recent case of a laparoscopic splenectomy were examined. Current literature related to this topic was reviewed. RESULTS: A 16-year-old girl underwent laparoscopic splenectomy for idiopathic thrombocytopenic purpura. Her preoperative platelet count was 96K. She was discharged on postoperative day 1 after an uneventful operation including division of the splenic hilum with an endoscopic linear stapler. On postoperative day 20, she presented with a 5-day history of epigastric pain, nausea, and low-grade fevers without peritoneal signs. Her white blood cell count was 17.3; her platelets were 476K. Computed tomography demonstrated thrombosis of the splenic, superior mesenteric, and portal veins propagating into the liver. Heparinization was begun followed by an unsuccessful attempt at pharmacologic and mechanical thrombolysis by interventional radiology. Over the next 5 days, her pain resolved, she tolerated a full diet, was converted to oral anticoagulation and sent home. Follow-up radiographic studies demonstrated the development of venous collaterals and cavernous transformation of the portal vein. DISCUSSION: No standard therapy for PVT exists; several approaches have been described. These include systemic anticoagulation, systemic or regional medical thrombolysis, mechanical thrombolysis, and surgical thrombectomy. Unanswered questions exist about the most effective acute therapy, duration of anticoagulation, and the potential efficacy of routine prophylaxis with perioperative antiplatelet agents. PVT following splenectomy occurs with both the open and laparoscopic approach.

Local resistance to oxidative stress by overexpression of copper-zinc superoxide dismutase limits neointimal formation after angioplasty.

PURPOSE: To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD). METHODS: The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing beta-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation. RESULTS: At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation byproducts were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582+/-0.088 for the nonviral control group versus 0.565+/-0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259+/-0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05). CONCLUSIONS: Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.

Superoxide dismutase mimetic m40401 reduces ischemia-reperfusion injury and graft coronary artery disease in rodent cardiac allografts.

BACKGROUND: The oxidative stress associated with ischemia-reperfusion (I/R) of cardiac allografts leads to production of injurious cytokines and expression of proinflammatory adhesion molecules. This is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). M40401 is a newly developed cell permeable superoxide dismutase mimetic, which has been shown to scavenge superoxide anion with highly specific and enhanced catalytic activity. We hypothesized that M40401 would exert a protective effect in I/R injury of cardiac allografts and ameliorate the progression of GCAD. METHODS: Recipient ACI rats were pretreated with M40401 or vehicle control. PVG donor hearts were heterotopically transplanted into the abdomen of ACI recipients. Cardiac allografts were analyzed for adhesion molecule mRNA expression and tumor necrosis factor-alpha expression after 4 hr of reperfusion. Neutrophil infiltration was detected by myeloperoxidase activity. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 mRNA were detected by reverse-transcriptase polymerase chain reaction. Immunohistochemical analysis of adhesion molecule expression was also performed. Additional grafts were procured 90 days after transplantation and assessed for the development of GCAD by computer-assisted image analysis. RESULTS: In the M40401-treated group, adhesion molecule expression was significantly less than in the vehicle control group. Treated grafts also had lower myeloperoxidase activity and tumor necrosis factor-alpha concentration compared with controls. Neointimal proliferation and intima to media ratios in M40401-treated allografts were significantly decreased compared with controls. CONCLUSIONS: Selective removal of superoxide anion by M40401 results in inhibition of I/R injury. Furthermore, M40401 treatment decreases the development of oxidative stress-associated GCAD. This treatment strategy may have broad cardioprotective applications for all cardiac operations in addition to cardiac transplantation.

Matrix metalloproteinase inhibition decreases ischemia-reperfusion injury after lung transplantation.

Increased microvascular permeability and extravasation of inflammatory cells are key events of lung ischemia-reperfusion (IR) injury. The purpose of this study was to investigate the role of matrix metalloproteinases (MMP) in IR-induced alveolar capillary membrane disruption after experimental lung transplantation. We used a rat model of lung orthotopic transplantation (n = 86) with a prolonged cold ischemic phase. MMP2 and MMP9 were elevated 4 h after the onset of ischemia and further increased during reperfusion. Compared to sham values, the alveolar-capillary membrane permeability increased by 105% and 82.6% after 4 h of ischemia and 2 h or 24 h of reperfusion, respectively. A 4- and 5-fold increase of the infiltration of ischemic tissue by neutrophils was also observed after 2 h and 24 h of reperfusion. The PO2/FIO2 ratio dropped significantly from 244 to 76.6 after 2 h of reperfusion and from 296.4 to 127.6 after 24 h of reperfusion. A nonselective inhibitor of MMP, administered to the rats and added to the preservation solution, reduced significantly the alveolar-capillary leakage, the transmigration of neutrophils and improved gas exchanges in animals submitted to 4 h of ischemia combined with 2 h or 24 h of reperfusion. We conclude that inhibition of MMP attenuates IR injury after experimental lung transplantation.

Bcl-2-mediated inhibition of apoptosis in rat cardiac allografts worsens development of graft coronary artery disease.

BACKGROUND: We hypothesized that adenovirally mediated Bcl-2 transfection of donor hearts would reduce the apoptosis that occurs during acute rejection while worsening the development of chronic graft coronary artery disease (GCAD). METHODS: PVG donor hearts were treated with either AdvBcl-2 or AdvNull virus before heterotopic transplantation into ACI rats. Bcl-2 expression was assessed on post-operative day 4 (POD) 4 by western blot. Apoptosis was measured using (99m)Technetium-bound-annexin V imaging and caspase 3 activity assay. Allograft survival was determined in a separate cohort of animals. Long-term-treated animals were then assessed for measures of GCAD on POD 90. RESULTS: Western blot analysis showed upregulation of Bcl-2 expression in AdvBcl-2-treated hearts. (99m)Tc-annexin V images demonstrated decreased uptake in the AdvBcl-2 group (1.41 +/- 0.33% vs 1.94 +/- 0.37%, p = 0.026). Caspase 3 activity was also significantly lower in this treatment group (0.112 +/- 0.032 vs 0.204 +/- 0.096, p = 0.049). Allograft survival was similar in both groups, respectively (7.7 +/- 1.2 vs 6.8 +/- 1.5 days, p = 0.340). GCAD, as determined by percent luminal narrowing (5.9 +/- 6.1% vs 1.6 +/- 1.5%, p = 0.039), intima-to-media ratio (5.1 +/- 5.1% vs 1.5 +/- 1.7%, p = 0.040) and percent of affected vessels (15.1 +/- 9.9% vs 5.3 +/- 4.4%, p = 0.009), was higher for the AdvBcl-2 group. CONCLUSION: Treatment of cardiac allografts with AdvBcl-2 resulted in a reduction of apoptosis that did not significantly improve short-term graft survival, but worsened chronic GCAD.

Quantification of mechanical stabilization for the performance of off-pump coronary artery surgery.

INTRODUCTION: Our objective was to analyze the motion of a coronary artery in 3-dimensional (3-D) space and to quantify the stabilization afforded by a mechanical arm using 3-D digital sonomicrometry. METHODS: The left anterior descending coronary artery (LAD) was exposed in swine (n = 7) via sternotomy. A 2-mm sonomicrometry crystal was sutured to the LAD, and an acrylic (Plexiglas) ring with 3 2-mm crystals fixed in an equilateral triangle was placed in the oblique pericardial sinus. Sonomicrometry measurements were obtained before and 10 minutes after placement of a stabilizing arm. Traces were analyzed for motion and velocity on a beat-to-beat basis in the x, y, and z planes by means of triangulation theory. Excursion was defined as the average maximum observed distance between LAD Cartesian positions p(k) = [px(k),py(k),pz(k)] over a beat such that the Excursion = max(j,k in beat) sqrt ([px(j) - px(k)]2 + [py(j) - py(k)]2 + [pz(j) - pz(k)]2). The maximum and the average of the Cartesian velocity magnitude, v = sqrt[vx(2) + vy(2) + vz(2)], were also calculated. RESULTS: Analysis of the LAD motion in planar space demonstrated a biphasic pattern in all 3 planes that appeared to be stable through the duration of the data acquisition period. The stabilizer dampened the motion of the LAD to a monophasic pattern and reduced the total distance traveled by the LAD crystal in all 3 planes. Stabilization resulted in a significant reduction of excursion, the maximum Cartesian velocity, and the average Cartesian velocity of the LAD. CONCLUSIONS: This method allows the precise quantification of LAD artery motion in 3-D space before and after the application of a stabilizing arm. We have demonstrated a significant reduction in the complexity of motion, the degree of motion in planar space, and the velocity of the LAD after application of a stabilizer.

Effects of adenoviral up-regulation of bcl-2 on oxidative stress and graft coronary artery disease in rat heart transplants.

BACKGROUND: Bcl-2 has been shown to have antioxidant properties. Early oxidative stress is an important antigen-independent factor that contributes to the development of graft coronary artery disease (GCAD). We hypothesized that adenoviral up-regulation of bcl-2 would decrease early oxidative stress and inhibit GCAD after heart transplantation. METHODS: PVG rat hearts were treated with adenovirus carrying the human bcl-2 gene (AdvBcl-2) or null adenovirus (AdvNull) then transplanted into the abdomens of PVG recipients. After 4 days of reperfusion to allow adenoviral gene expression, grafts were retransplanted into ACI rat recipients and reperfused for 4 or 8 hours or 90 days (cyclosporine A 7.5 mg/kg on postoperative day [POD] 0-9). Production of tumor necrosis factor (TNF)-alpha after 4 hours and oxidized glutathione (GSSG) after 8 hours indicated development of oxidative stress. 90-day allografts were assessed for GCAD by way of computerized morphometry. RESULTS: Over-expression of bcl-2 at the time of allograft reperfusion was confirmed by Western blotting. Whereas AdvNull-treated hearts demonstrated elevated TNF-alpha levels after 4 hours and increased GSSG after 8 hours of reperfusion, AdvBcl-2-treated hearts were no different from nontransplanted hearts. AdvBcl-2 treatment also resulted in decreased luminal narrowing and intima-to-media ratio at POD 90. CONCLUSIONS: Bcl-2 over-expression interrupts the development of oxidative stress in reperfused rat-heart allografts. Early up-regulation of bcl-2 also decreases GCAD, indicating the importance of early oxidative stress and the role that bcl-2 may play in the long-term function of heart transplants.

Elevated cyclic adenosine monophosphate ameliorates ischemia-reperfusion injury in rat cardiac allografts.

BACKGROUND: Oxidative stress after ischemia and reperfusion leads to leukocyte activation, the production of injurious cytokines, and increased expression of inflammatory adhesion molecules. This initial event is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). Cyclic adenosine monophosphate (cAMP) is an important second messenger that inhibits the expression of tumor necrosis factor alpha (TNF-alpha), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1) in vitro. Its levels decrease during organ preservation. We hypothesized that augmenting allograft cAMP levels with the water-soluble adenylate cyclase activator, NKH477, could decrease ischemia-reperfusion injury and inhibit the progression of GCAD. METHODS: PVG to ACI rat heterotopic cardiac allografts, treated with NKH477 solution or vehicle, were reperfused for 4 hours or 90 days after 60 minutes of ischemia. We analyzed grafts for intracellular adhesion molecule 1 (ICAM-1), VCAM-1, and ELAM-1 mRNA expression; TNF-alpha and interleukin-6 (IL-6) protein expression; and myeloperoxidase activity. We also performed immunohistochemical analysis for ICAM-1 and VCAM-1 protein expression. At post-operative Day 90, the progression of GCAD had increased morphometrically. RESULTS: NKH477-treated grafts had significantly decreased levels of myeloperoxidase activity compared with controls. In this group, TNF-alpha, IL-6, and VCAM-1 protein expression was inhibited; however, ICAM-1 and ELAM-1 expression did not alter. We found no differences in the degree of development of GCAD between groups. CONCLUSION: Although augmented intracellular cAMP prevented acute reperfusion injury, it was insufficient to prevent the development of GCAD. Intracellular adhesion molecule 1 and ELAM-1, whose expression NKH477 does not inhibit, may play important roles in the development of GCAD.

Ex vivo blockade of endothelin-1 inhibits graft coronary artery disease in a rodent cardiac allograft model.

BACKGROUND: Graft coronary artery disease (GCAD) is characterized by vascular narrowing resulting from intimal hyperplasia. Endothelin (ET)-1, derived from the vascular endothelium and macrophages, stimulates vascular smooth muscle cells (SMCs), which leads to neointimal formation in donor graft coronary arteries. In this study, we hypothesized that antisense (AS) oligodeoxynucleotides (ODN) for preproendothelin-1 (ppET-1) delivered to rat cardiac allografts by means of hyperbaric pressure would reduce the incidence of GCAD. METHODS: PVG donor hearts were infused with ppET-1 AS ODN (80 micromol/liter), sense ODN, scrambled ODN or saline alone and incubated in a pressure chamber at 75 psi or ambient pressure for 45 minutes. Cardiac allografts were heterotopically transplanted into ACI rats treated with cyclosporine (7.5 mg/kg, Days 0 to 9). Allografts were procured at post-operative days (POD) 7 or 90. Reverse transcription-polymerase chain reaction (RT-PCR) assay for ET-1 mRNA and ET01 immunohistochemistry (IHC) were performed at PODs 7 and 90. Elastic staining and IHC with anti-macrophage and alpha-SMC actin antibodies were performed to assess GCAD at POD 90. RESULTS: Treatment with AS ODN and pressure significantly reduced ET-1 mRNA and protein expression. A significant reduction in GCAD was achieved with inhibition of ET-1 and was associated with attenuation of macrophages and SMCs in the neointima. CONCLUSION: Peri-operative ex vivo inhibition of ET-1 expression results in a reduction of GCAD. This highly targeted therapy may be a clinically viable strategy for the prevention of ET-1-induced GCAD following cardiac transplantation.

Up-regulation of Bcl-2 through hyperbaric pressure transfection of TGF-beta1 ameliorates ischemia-reperfusion injury in rat cardiac allografts.

BACKGROUND: Oxidative stress after ischemia-reperfusion of cardiac allografts leads to activation of cardiomyocytes and production of cytokines. Bcl-2, an inhibitor of the apoptotic pathway, also has strong antioxidant properties. Ischemia-reperfusion injury after transplantation leads to decreased bcl-2 and increased tumor necrosis factor (TNF)-alpha levels. Transforming growth factor (TGF)-beta1 is known to attenuate ischemia-reperfusion injury and inhibits apoptosis of myofibroblasts. We hypothesize that TGF-beta1, prevents bcl-2 cleavage and increased TNF-alpha production. METHODS: Rat PVG donor hearts were heterotopically transplanted into ACI recipients. Donor hearts were procured and assigned to groups: (1) intracoronary TGF-beta1 (200 ng/ml) perfusion and pressure at 78 psi for 45 minutes (n = 4); (2) intracoronary TGF-beta1 perfusion and incubation for 45 minutes without pressure (n = 4), (3) saline perfusion and incubation for 45 minutes without pressure (n = 4). Hearts were procured 4 hours after transplantation and analyzed by reverse transcriptase-polymerase chain reaction for bcl-2 mRNA expression, ELISA for TNF-alpha, and for myeloperoxidase activity (MPO). RESULTS: Bcl-2 decreased in untreated animals (bcl-2:G3PDH ratio = 0.85 +/- 0.73 vs 1.16 +/- 0.11, not significant [NS]), whereas TNF-alpha increased to 669.99 +/- 127.09 vs 276.84 +/- 73.65 pg/mg total protein in controls (p < 0.003). In TGF-beta(1) pressure-treated hearts, bcl-2 was up-regulated (2.49 +/- 0.6 vs 1.16 +/- 0.11, controls, p < 0.005), whereas TNF-alpha was unchanged (396.1 +/- 100.38 vs 276.84 +/- 73.65 pg/mg, NS). Hearts treated with TGF-beta1 and pressure showed significant up-regulation of bcl-2 compared with hearts treated with TGF-beta1 without pressure (2.49 +/- 0.6 vs 1.17 +/- 0.6, p < 0.02). MPO showed no differences. CONCLUSIONS: Bcl-2 is down-regulated and TNF-alpha up-regulated in this model of ischemia-reperfusion injury. Furthermore, TGF-beta1 is linked to this process and ameliorates reperfusion injury by up-regulating bcl-2 and inhibiting TNF-alpha. Therapeutic overexpression of myocardial TGF-beta1 may be clinically useful to control ischemia-reperfusion injury associated with cardiac transplantation.

Heart transplantation: a thirty-year perspective.

Heart transplantation has evolved over the past 30 years into a mainstay of therapy for heart failure patients. As the surgical technique and basic immunology were defined, heart transplantation became a real therapeutic option. Over the next few decades, thoracic transplant teams at Stanford University and other institutions refined this mode of therapy. This review addresses the history, current surgical technique, recipient and donor selection, postoperative care, immunosuppression, short- and long-term complications, and clinical outcomes associated with this procedure.