Position paper of the Ethics Committee of the International Xenotransplantation Association

Xenotransplantation (XTx) provides a potential solution to the shortage of human organs and tissues, and has several advantages over other possible solutions to this problem. However, a number of scientific and ethical barriers exist, and need to be addressed in order to advance the field of XTx in a manner that optimizes its potential to benefit society and minimizes its risk. Some of the most pressing ethical issues are discussed, and the position of the Ethics Committee of the International Xenotransplantation Association is presented.     

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Paraurethral leiomyoma

Paraurethral leiomyoma is a rare, benign, hormone-dependent neoplasm of mesenchymal origin affecting women. The clinical evidence varies, but it tends to be asymptomatic or associated with the sensation of a foreign body; urinary symptoms are rarely described. The distinction among urethral, paraurethral, and anterior vaginal wall leiomyoma can be very difficult owing to their anatomic proximity. Excision of the mass is the recommended treatment, and the diagnosis is confirmed by the pathologic finding to rule out the presence of a sarcoma. A case of paraurethral leiomyoma associated with dysuria, dyspareunia, and obstructive voiding symptoms is reported.     

Infrapopliteal Angioplasty for Limb Salvage in the Setting of Renal Failure: Do Results Justify Its Use?

Multiple reports advocate the use of infrapopliteal angioplasty for limb salvage; however, its utility in the setting of renal failure is unclear. We performed angioplasty, rather than bypass, for tibial stenoses or occlusions <3 cm on 90 limbs of 79 patients (64.4% male, mean age 67.2 years), all with ischemic ulcer. Seventy (77.8%) had diabetes mellitus and 16 (17.8%) had end-stage renal disease (ESRD). Mean follow-up was 14.3 months (range 0.3-45). Associated femoropopliteal revascularization was required in 28 (31.0%) limbs. Primary angiographic success was achieved in 83 (92.2%) limbs. Residual stenosis or thrombosis occurred in two and five limbs, respectively. Dissection occurred in six limbs, all successfully treated with stent placement. Ulcer healing occurred after initial angioplasty in 41 (55.4%) non-ESRD and four (25%) ESRD limbs. Subsequent revascularization procedures were required in 21 (23.3%) limbs, including six bypasses and 15 repeat angioplasties, of which three underwent subsequent bypasses. Major amputation was required in 11 (14.9%) non-ESRD and seven (43.7%) ESRD limbs. Limb salvage was 84.4% and 80.2% in those without and 52.5% and 52.5% in those with ESRD at 1 and 3 years, respectively (p = 0.01). Thirty-day mortality was 2.2%. Overall actuarial survival was 82.2% and 62.1% at 1 and 3 years, respectively, and did not differ significantly between patients with and without ESRD (p = 0.66). Infrapopliteal angioplasty is a safe technique with low procedural morbidity and mortality. However, the inferior wound-healing and limb-salvage rates observed in patients with renal failure bring to question the utility of infrapopliteal angioplasty in this population. Presented at the Fifteenth Annual Winter Meeting of the Peripheral Vascular Surgery Society, Steamboat Springs, CO, January 28-30, 2005.     

The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury. MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury. RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver. CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.     

Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.     

Orthotopic liver transplantation with vena cava preservation in cirrhotic patients: is systematic temporary portacaval anastomosis a justified procedure?

INTRODUCTION: We evaluated the peri- and postoperative effects of the lack of a temporary portocaval anastomosis (TPCA) during orthotopic liver transplantation (OLT) in 84 patients with cirrhosis. PATIENTS AND METHODS: From December 1996 to December 2002, 156 liver transplant recipients included (54%; 60 men and 24 women) of mean age 52 +/- 9 years with portal hypertension. In whom peri- and postoperative data were analyzed. RESULTS: The median fall in mean arterial pressure upon vascular clamping and unclampings was 20 mm Hg (range 15 to 75), while the median duration of portal vein clamping was 77 minutes. The median amount of blood autotransfusion was 1100 mL (range 0 to 5400). The median number of red blood cell and fresh-frozen plasma units transfused were 5 and 6.5, respectively. The median intraoperative urinary output was 72 mL/h (range 11 to 221). Three patients (3.5%) presented a perioperative complication, but no perioperative death was observed. Six patients experienced an early postoperative complication (<10 days): five hemodynamic complications and one transient renal failure, which did not require hemodialysis. One patient (1%) died at 12 hours after OLT from acute pulmonary edema. CONCLUSION: This study shows that systematic TPCA during OLT with preservation of the native retrohepatic vena cava in cirrhotic patients does not appear to be justified. In contrast, peri- and postoperative hemodynamic parameters as well as blood component requirements were comparable to those of the literature reporting OLT with straightforward TPCA.     

Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open‐heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m². The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20‐min test during which CPB was adjusted to the minimum flow to maintain MVO₂ >70% and rSO₂ >45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2 >70% and rSO2 >45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20‐min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.     

IS20I,a specific alphavbeta3 integrin inhibitor,reduces glioma growth in vivo

OBJECTIVE: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS20I on human malignant gliomas. METHODS: The in vitro effects of IS20I were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS20I was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS: IS20I reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS20I strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS20I induced endothelial and tumor cell apoptosis. In vivo, when IS20I was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS20I inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo.