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.

Targeted endothelial delivery of nanosized catalase immunoconjugates protects lung grafts donated after cardiac death.

BACKGROUND: Donor organ shortage represents a major problem in lung transplantation. Donation after cardiac death could help to expand the pool of organs, but the additional period of warm ischemia after cardiac arrest aggravates primary graft dysfunction. The pulmonary endothelium of the graft constitutes an important source and target of reactive oxygen species generated during ischemia and reperfusion. Targeted protection of graft pulmonary endothelial cells by the antioxidant enzyme catalase, conjugated with a platelet/endothelial cell adhesion molecule-1 (PECAM-1) antibody to nanosized particles (anti-PECAM/catalase conjugates), might improve outcome in lung transplantation using donors after cardiac death and prolonged hypothermic preservation. METHODS: Left lung transplantation was performed in 18 pigs. Before cardiac arrest, donors received anti-PECAM/catalase, unconjugated component mixture or vehicle solution. After 90-min warm and 18-hr hypothermic ischemia, lungs were transplanted, and function was assessed during 6 hr after reperfusion. Samples of bronchoalveolar lavage fluid and lung tissue were taken thereafter. Six sham-operated animals served as controls. RESULTS: During 6-hr reperfusion, anti-PECAM/catalase significantly ameliorated graft function, evidenced by major improvements of gas exchange and reduced intrapulmonary shunt fraction. Furthermore, lipid peroxidation, alveolar leakage, and edema formation were reduced in protected grafts. Similarly moderate lung pathology was seen after transplantation. CONCLUSIONS: Augmentation of the antioxidant capacity of graft pulmonary endothelial cells with anti-PECAM/catalase nanoparticles represents a straightforward approach to enable a safe transplantation of prolonged preserved donation after cardiac death lungs. Anti-PECAM/catalase protection alleviated oxidative stress and allowed immediate reconstitution of normal gas exchange and pulmonary microcirculation, a prerequisite for improved graft and patient outcome.

Arterial blood flow predicts graft survival in liver transplant patients.

Proper liver perfusion is essential for sufficient organ function after liver transplantation. The aim of this study was to determine the effects of portal and arterial blood flow on liver function and organ survival after liver transplantation. The arterial and portal venous blood flow was measured intraoperatively by transit time flow measurement after reperfusion for 290 consecutive liver transplants. The graft survival, hepatic cell damage (alanine aminotransferase and aspartate aminotransferase), and liver function (prothrombin ratio and bilirubin) were determined. Grafts were stratified into groups according to arterial blood flow measurements [<100 mL/minute for arterial blood flow group I (ART I), 100-240 mL/minute for ART II, and ≥ 240 mL/minute for ART III] and portal venous blood flow measurements (<1300 mL/minute for portal venous blood flow group I and ≥ 1300 mL/minute for portal venous blood flow group II). With multivariate analysis, the impact of blood flow on graft survival was determined, and potential confounders were considered. Decreased portal venous blood flow was associated with significantly less organ survival in univariate analysis but not in multivariate analysis. In contrast, the arterial blood flow was significantly correlated with organ survival after liver transplantation in univariate and multivariate analyses [hazard rate ratio = 2.5, confidence interval = 1.6-4.1, P < 0.001, median survival = 56.6 (ART I), 82.7 (ART II), or 100.7 months (ART III)]. Moreover, low arterial blood flow resulted in impaired postoperative organ function and higher rates of primary nonfunction. Biliary complications were not affected by blood flow. Other risk factors for graft failure that were identified by multivariate analysis included retransplantation, histidine tryptophan ketoglutarate solution versus University of Wisconsin solution, and donor treatment with epinephrine. Impaired arterial blood flow after reperfusion represents a significant predictor of primary graft nonfunction and is associated with impaired graft survival. Whether the intraoperative measurement of hepatic arterial flow is predictive of graft survival should be evaluated in a prospective trial.

The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage.

OBJECTIVE: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage. DESIGN: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry. RESULTS: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from trauma-hemorrhage animals depressed MHC class II expression of CD11c(+) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage. CONCLUSIONS: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage.

Antiviral therapy for recurrent hepatitis C after liver transplantation: sustained virologic response is related to genotype 2/3 and response at week 12.

OBJECTIVES: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is a major cause of transplant failure in HCV-positive patients. We retrospectively assessed the efficacy and safety of antiviral therapy and determined the factors influencing sustained virologic response (SVR) in LT recipients. METHODS: Between 1998 and 2007, we treated 36 LT recipients for hepatitis C cirrhosis and subsequent HCV recurrence (27 genotype 1 and 9 genotypes 2/3) with pegylated interferon alpha-2a (180 microg/week), pegylated interferon alpha-2b (1.5 microg/kg per week), or standard interferon alpha-2b (3 MIU 3X/week) plus ribavirin (600-1200 mg/day) for 48 weeks. RESULTS: SVR was achieved in seven of 27 (26%) of genotype 1 patients versus nine of nine (100%) genotype 2/3 patients (P=0.0001). Early virologic response at week 12 was associated with permanent viral clearance. Side effects included cytopenia and acute hearing loss, but rate of therapy withdrawal and dose reduction was low. CONCLUSION: Combination therapy in patients with HCV reinfection after LT yields an excellent SVR rate in genotype 2/3 patients, but remains unsatisfactory in genotype 1 patients. Virologic response at week 12 (early virologic response) can determine whether therapy should be continued or not.

Effect of graft steatosis on liver function and organ survival after liver transplantation.

BACKGROUND: It was the aim to determine the effect of graft steatosis on intraoperative organ blood flow, postoperative liver function, and organ survival. METHODS: A total of 225 consecutive liver transplants were reviewed. Liver blood flow, hepatic function (AST, ALT, prothrombin time), and organ survival were determined. Donor liver grafts were categorized into 2 subgroups: mild (<30%) (n = 175) and moderate to severe (>/=30%) (n = 50) macrovesicular steatosis. RESULTS: Moderate to severe steatosis was associated with significantly increased AST and ALT levels and significantly diminished prothrombin time on the first and second postoperative day. By day 7 differences in liver function were no longer evident. Organ blood flow was not affected by steatosis. After adjustment for potential confounders, organ survival did not depend on the degree of donor steatosis (5-year-survival rates: 68% and 58% with steatosis <30%, or >/= 30%, respectively) (hazard ratio .754, confidence interval .458-1.242, P = .268). CONCLUSION: Steatotic livers can be transplanted safely with good results for long-term organ survival if other contraindications are absent.

Predictors of general complications after video-assisted thoracoscopic surgical procedures.

BACKGROUND: The video-assisted thoracoscopic approach has become the preferred method for many procedures due to the reduced trauma, complication rate and morbidity. The aim of this study was a risk evaluation of patients undergoing video-assisted thoracoscopic surgery (VATS) procedures. METHODS: Between 1991 and 2004, 1,008 patients were included in this single-center retrospective analysis. Risk assessment was performed using univariate and multivariate analysis. RESULTS: Multivariate analysis revealed that patient age (p = 0.003), the duration of the VATS procedure (p = 0.008), redo-VATS (p < 0.001) and conversion to open thoracotomy (p < 0.001) correlated significantly with the incidence of complications. Patients with immune deficiency following organ transplantation had the highest complication rate at 31.7%, which was significantly higher than for patients with either benign disease (p = 0.010) or malignant disease (p = 0.019). CONCLUSIONS: VATS is a safe procedure, but extra caution is recommended for patients with a higher risk profile (age, redo-VATS, immune deficiency).

The role of L-arginine following trauma and blood loss.

PURPOSE OF REVIEW: Vascular endothelial cells control vascular smooth muscle tone via the release of nitric oxide. Following adverse circulatory conditions, namely trauma and hemorrhage, endothelial cell dysfunction occurs, leading to a decrease in the release of endothelium-derived nitric oxide, which contributes to further alterations in tissue perfusion and organ function. RECENT FINDINGS: Early administration of L-arginine (the precursor of nitric oxide) and the substrate for nitric oxide synthase in vascular endothelial cells has been found to restore the depressed organ blood flow and to reduce tissue injury following shock. This improvement in cardiovascular function was associated with restoration of the depressed cell-mediated immune responses and attenuation of the massive inflammatory response encountered under such conditions. Furthermore, the excessive infiltration of the liver with neutrophils following trauma-hemorrhage was decreased by L-arginine administration, thereby reducing hepatic injury. In addition, L-arginine treatment decreased the inflammatory response at the site of trauma and the improved wound-healing process following blood loss. SUMMARY: Despite those promising results in animal models at present, none of the published clinical trials has demonstrated efficacy of L-arginine at doses above standard dietary practices on the outcome in critically ill surgical patients, besides the reduction in infectious complications.

Surgical treatment of primary biliary cirrhosis and primary sclerosing cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are progressive cholestatic liver diseases of supposed auto-immune etiology. The clinical course is unpredictable and, in many patients, leads to end-stage liver disease or a poor quality of life. Conservative therapy only has a limited effect on the natural history, but orthotopic liver transplantation(OLT) offers a definitive therapeutic option. Retrospective analysis was performed for 38 patients with PBC and 17 patients with PSC who underwent OLT between January 1986 and June 2003 at our institution. Median followup after OLT was 72 mo.Cumulative survival at 5 yr post-OLT was 84% in the PBC group and 73% in the PSC group. Compared with OLT for other benign diseases, actuarial survival rates at 5 and 10 yr post-OLT were significantly better for patients with PBC, whereas there was no difference in survival after OLT for patients with PSC. Survival rate at 5 yr post-OLT was significantly increased for patients with PBC who had a Child-Pugh B liver cirrhosis (93%) compared with those who had Child-Pugh C cirrhosis (60%). Retransplantation rate was 18.2% (resulting from biliary complications in three cases). Surgical techniques had no effect on outcome after OLT in both groups. We concluded that liver transplantation represents a safe and beneficial therapy for patients with end-stage PBC. Cirrhotic patients with PSC also benefit from OLT, with an outcome comparable to that of liver cirrhosis of other etiologies.

Continuous infusion of nitroglycerin improves pulmonary graft function of non-heart-beating donor lungs.

BACKGROUND: The warm ischemic period of lungs harvested from a non-heart-beating donor (NHBD) results in an increased ischemia-reperfusion injury after transplantation. The intravenous application of nitroglycerin (NTG), a nitric oxide (NO) donor, proved to be beneficial during reperfusion of lung grafts from heart-beating donors. The objective of the present study was to investigate the effect of nitroglycerin on ischemia-reperfusion injury after transplantation of long-term preserved NHBD-lungs. METHODS: Sixteen pigs (body weight, 20-30 kg) underwent left lung transplantation. In the control group (n=5), lungs were flushed (Perfadex, 60 mL/kg) and harvested immediately after cardiac arrest. In the NHBD group (n=5) and the NHBD-NTG group (n=6), lungs were flushed 90 min (warm ischemia) after cardiac arrest. After a total ischemia time of 19 hr, lungs were reperfused and graft function was observed for 5 hr. Recipient animals in the NHBD-NTG group received 2 microg/kg/min of NTG administered intravenously during the observation period starting 5 min before reperfusion. Tissue specimens and bronchoalveolar lavage fluid (BALF) were obtained at the end of the observation period. RESULTS: Compared with the control group, pulmonary gas exchange was significantly impaired in the NHBD group, whereas graft function in the NHBD-NTG group did not change. Leukocyte fraction and protein concentration in the BALF and histologic alteration of the NHBD-NTG group were not different from controls. CONCLUSIONS: Continuous infusion of NTG in the early reperfusion period improves pulmonary graft function of NHBD lungs after long-term preservation. The administration of an NO donor during reperfusion may favor the use of NHBD lungs to alleviate the critical organ shortage in lung transplantation.

Chlamydia pneumoniae in atherosclerotic lesions of patients undergoing vascular surgery.

The pathophysiological implications of Chlamydia pneumoniae in atherosclerotic lesions and its contribution to atherosclerotic complications remain unclear. Therefore, the purpose of the present study was to evaluate whether or not there is an association between the presence of Chlamydia pneumoniae in atherosclerotic lesions and the clinical manifestations as well as risk factors of atherosclerotic disease in patients undergoing vascular surgery. Specimens from atherosclerotic arteries were collected during endarterectomy of the carotid artery (n = 15), endarterectomy of the femoral artery (n = 19), or repair of an abdominal aortic aneurysm (n = 28). Detection of Chlamydia pneumoniae was performed by using immunohistochemical staining (IHC) with specific antibodies. Clinical manifestations of atherosclerotic disease were defined by the presence of cardiovascular risk factors, coronary heart disease, and previous vascular surgery. Inflammatory serum markers were determined in all patients prior to surgery. The specimens of all 62 patients revealed severe atherosclerosis in histological examination and a positive IHC was observed in 41 samples (66%). There were no differences regarding cardiovascular risk factors, coronary heart disease, events of previous vascular surgery, or inflammatory serum markers when comparing patients with positive and negative IHC. In conclusion, our findings showed no correlation between clinical or laboratory parameters of atherosclerosis and the presence of Chlamydia pneumoniae in atherosclerotic lesions. Therefore, Chlamydia pneumoniae appears to be a concomitant phenomenon rather than a causative principle in atherosclerosis.

Tissue damage of non-heart-beating donor lungs after long-term preservation: evaluation of histologic alteration, bronchoalveolar lavage, and energy metabolism.

Several studies have shown that warm ischemia before short-term preservation of pulmonary grafts from non-heart-beating donors (NHBD) induced morphological changes, but still provided a good pulmonary graft function. The aim of this study was to investigate morphological and metabolic changes of NHBD lungs after long-term preservation. Left lung allotransplantation was performed on 12 native-bred pigs. In the NHBD group, lungs were subjected to 90 min of warm ischemia before harvesting, whereas lungs in the HBD group were harvested immediately after cardiac arrest. After a total ischemic period of 19 h, lungs were reperfused and pulmonary gas exchange was assessed. Bronchoalveolar lavage (BAL) and tissue specimen for wet-to-dry weight (W/D) ratio, histologic examination, and measurement of high-energy phosphates were taken 5 h after reperfusion. All parameters were compared with a sham-operated control group. Five hours after reperfusion, mean paO2 and paCO2 were 288 +/- 52 and 48 +/- 0.8 mmHg, respectively, during isolated ventilation of the pulmonary graft with 100% oxygen in the NHBD group. W/D ratio and high-energy phosphates of the pulmonary graft did not differ between our study groups. Histologic examination showed significant morphological changes in the HBD and NHBD group, but alterations were more pronounced in the NHBD group. The percentage of neutrophils, total protein content, and potassium concentration were significantly elevated in the BAL fluid of the NHBD group. Despite the observed aggravation of cellular injury after long-term preservation, NHBD lungs still performed a good pulmonary graft function.