Stent versus open surgery for acute and chronic traumatic injury of the thoracic aorta: a single-center experience

BACKGROUND: Traumatic injuries of the thoracic aorta have a high morbidity and mortality. Treatment options include either open surgery or endovascular stent graft implantation. METHODS: We have reviewed retrospectively all our patients treated for acute and chronic traumatic injury of the thoracic aorta and compared the outcome of the endovascular versus open therapy. Age, gender, severity of injuries, interventional delay, perioperative morbidity, 30-day mortality, length of intensive care, and overall hospital stay were evaluated. RESULTS: In all, 46 patients were treated over the past 14 years. Overall 30-day mortality was 16% in patients treated for acute or contained aortic ruptures (n = 31) and not significantly different after endovascular versus open repair (13.3% versus 18.8%). There was no mortality in the patients receiving elective stent grafting or open surgery for chronic posttraumatic aortic aneurysms (n = 15). Conversion and/or operative revision following stent graft implantation occurred in three patients (12.5%). Neurologic complications were absent in the stent graft group (0 of 24), whereas paraplegia (n = 2) or minor neurologic (n = 3) deficits developed following open surgery (5 of 22; 22.7%; p = 0.013). Length of intensive care and overall hospital stay were significantly shorter for patients after elective stent graft treatment compared with open surgery (p = 0.045). CONCLUSIONS: According to our midterm results, minimally invasive endovascular repair for patients with acute traumatic ruptures and chronic posttraumatic aneurysms is an equally effective treatment option compared with open surgery, with advantages regarding perioperative neurologic complications and duration of hospital stay under elective circumstances.     

Temporary intraoperative porto‐caval shunt: useless or beneficial in piggy back liver transplantation?

The role of intraoperative porto‐caval shunts in orthotopic liver transplantation (OLT) is controversial. Aim of this study was to analyze the effects of an intraoperative, porto‐caval catheter‐shunt on graft function and survival following cava sparing OLT. Four hundred and forty‐eight piggy back liver transplantations with or without a temporary spontaneous porto‐caval shunt between 1997 and 2010 were analyzed (shunt n = 274 vs. no shunt n = 174). Lab MELD scores and donor risk indices (DRI) were calculated. Hepatic injury (ALT, AST), ‐function (bilirubin, prothrombin ratio), postreperfusion liver blood flow and graft survival were registered [mean follow‐up: 50.5 (0–163.0) months]. The impact of a shunt on graft survival was determined using multivariate analysis. Usage of a porto‐caval shunt was associated with reduced hepatic injury (ALT, AST), whereas graft function was not affected. The shunt group showed a significantly increased portal venous blood flow after reperfusion. Retransplantation rate was decreased (7.7% vs. 20.1%, P = 0.001) and long‐term graft survival was significantly increased with a porto‐caval shunt (hazard ratio 2.1, P < 0.001). This effect was even more pronounced for marginal organs. Usage of intraoperative porto‐caval catheter‐shunts is beneficial in cava sparing OLT and is associated with reduced ischemia‐reperfusion injury and improved organ survival in particular for recipients of marginal organs.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Immunologic considerations for therapeutic strategies utilizing allogeneic hepatocytes: hepatocyte-expressed membrane-bound major histocompatibility complex class I antigen sensitizes while soluble antigen suppresses the immune response in rats

Understanding the immunologic effects of hepatocytes is critical because of the potential to use these cells for bioartificial livers, as a vehicle for gene transfer, and as a means to induce donor-specific immunosuppression in organ transplantation. However, this understanding is complicated by the fact that hepatocytes express membrane-bound and soluble forms of major histocompatibility complex (MHC) class I antigen, each with the potential to induce different immune responses. In the present study we first determined the immunologic effect of normal donor-derived hepatocytes in a rat heart transplant model. We then used ex vivo hepatocyte gene transfer to examine the immunologic effects of different forms of hepatocyte-expressed MHC class I antigen. Results showed that intrasplenic injection of purified, donor-strain-specific hepatocytes into recipients primes alloimmunity, as evidenced by acceleration of heart allograft rejection. Interestingly, injection of autologous hepatocytes transfected ex vivo with DNA encoding only membrane-bound donor MHC class I antigen (RT1.A(a)) also accelerated allograft rejection. However, hepatocytes transfected to express only secreted donor MHC antigen prolonged transplant survival. Limiting-dilution analysis of lymphocytes from animals treated with hepatocytes producing only secreted alloantigen showed an antigen-specific reduction in cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) precursors. Further analysis of CTL populations by flow cytometry revealed a relatively high percentage of nonviable cells, implying that soluble antigen promotes allospecific CTL death. In summary, this study suggests that hepatocyte-expressed MHC class I molecules have opposing immunologic effects, with the membrane-bound antigen inducing immunologic sensitization, and the soluble antigen promoting donor-specific immunosuppression.     

Diclofenac drops to treat inflammation after cataract surgery

PURPOSE: To compare the anti-inflammatory effect of topical diclofenac sodium 0.1% in a fixed combination with gentamicin 0.3% to the anti-inflammatory effect of dexamethasone phosphate 0.1% in a prospective randomized double-masked double-dummy study in patients undergoing cataract surgery. SETTING: Trial performed from June 1991 to April 1992 at the H?pital Jules Gonin, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland. METHODS: Inclusion of patients scheduled for extracapsular cataract extraction (ECCE) with implantation of an all PMMA intraocular lens (IOL). Double-masked comparison of post-operative inflammation in two randomized treatment groups: (1) fixed diclofenac sodium 0.1%/gentamicin 0.3% and vehicle drops 4X/day until day 12-14 and diclofenac sodium 0.1% 3X/day until day 28. (2) dexamethasone phosphate 0.1% drops 4X/day until postoperative day 12-14 and 3X/day until day 28 and gentamicin 0.3% drops 4X/day until day 12-14. Anterior chamber flare and cells, measured by laser flare-cell photometry, were analyzed as the primary outcomes. RESULTS: Eighty-seven patients were recruited, 45 being assigned to the diclofenac group and 42 to the dexamethasone control group. Diclofenac was significantly better than dexamethasone at controlling flare at day 3 (p< or =0.01) and day 12-14 (p< or =0.002). Mean anterior chamber cells were also significantly lower at day 12-14 (p< or =0.021) and day 28 (p< or =0.012). The commonest adverse event was transient punctate keratitis, which occurred in 15 diclofenac and 3 dexamethasone patients. CONCLUSIONS: While both treatments were effective at controlling post-operative inflammation, the diclofenac-gentamicin combination followed by diclofenac alone was significantly better at suppressing flare and cells but showed a slightly higher incidence of punctate keratitis and eye discomfort.     

Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth,metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice

Vascular endothelial growth factor (VEGF) is the major pro-angiogenic factor for most tumors. VEGF expression has been shown to be associated with a poor prognosis in human pancreatic cancer. The purpose of our study was to determine the effect of blockade of VEGF receptor-2 activity with or without gemcitabine on tumor growth and metastasis in an orthotopic model of human pancreatic cancer in nude mice. Therapy with gemcitabine or DC101, a VEGF receptor-2 antibody, resulted in a significant reduction of primary pancreatic tumor growth compared to untreated controls. The combination of DC101 and gemcitabine inhibited primary pancreatic tumor growth and lymphatic metastasis to a greater degree than either agent alone. Treatment with DC101 decreased vessel counts and increased the area of hypoxic tumor tissue compared to controls. Immunofluorescent double staining for apoptotic endothelial cells demonstrated a significant increase in the number apoptotic endothelial cells 24 days after initiation of therapy with DC101 plus gemcitabine. DC101 plus gemcitabine also increased tumor cell death and decreased tumor cell proliferation in pancreatic tumors. These findings indicate that blockade of VEGF receptor activation interferes with the survival of tumor endothelial cells, resulting in a reduction of primary pancreatic tumor growth in nude mice. Furthermore, the data demonstrate that anti-VEGF receptor-2 therapy potentiates the tumoricidal effect of gemcitabine in this model. Anti-VEGF receptor-2 therapy in combination with gemcitabine may be a novel therapeutic approach for advanced pancreatic cancer.