Chondroma of the Sternum Growing in a Pregnant Patient: A Case Report.

PURPOSE: Benign tumors are known to grow or develop sometimes during pregnancy. We present a case report about a young woman with a growing sternal tumor. METHODS: After her second pregnancy, a 32-year-old female presented with a rapid growing sternal tumor. Computed tomography (CT) scan revealed a tumor measuring 10 × 8 × 7 cm with an intrathoracic bulk, compressing the heart and the upper margin of the liver. RESULTS: Resection of the tumor was performed uneventfully. Histologic examination of the resected mass revealed a chondroma. CONCLUSION: To the best of our knowledge, this is the first report of a huge sternal chondroma growing in a pregnant patient. There is not often a need to treat these patients before delivery, however, thereafter surgical treatment of growing tumors is recommended.

The value of hepatic resection in metastasic renal cancer in the Era of Tyrosinkinase Inhibitor Therapy.

BACKGROUND: The value of liver-directed therapy (LDT) in patients with metastasic renal cell carcinoma (MRCC) is still an active field of research, particularly in the era of tyrosinkinase inhibitor (TKI) therapy. METHODS: The records of 35 patients with MRCC undergoing LDT of metastasic liver lesions between 1992 and 2015 were retrospectively analyzed. Immediate postoperative TKI was given in a subgroup of patients after LDT for metastasic lesions. Uni- and multivariate models were applied to assess overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS). RESULTS: Following primary tumor (renal cell cancer) resection and LDT, respectively, median OS was better for a total of 16 patients (41 %) receiving immediate postoperative TKI with 151 and 98 months, when compared to patients without TKI therapy with 61 (p = 0.003) and 40 months (p = 0.032). Immediate postoperative TKI was associated with better median PFS (47 months versus 19 months; p = 0.023), whereas in DFS only a trend was observed (51 months versus 19 months; p = 0.110). CONCLUSIONS: LDT should be considered as a suitable additive tool in the era of TKI therapy of MRCC to the liver. In this context, postoperative TKI therapy seems to be associated with better OS and PFS, but not DFS.

The value of liver resection for focal nodular hyperplasia: resection yes or no?

BACKGROUND: Focal nodular hyperplasia (FNH) are benign lesions in the liver. Although liver resection is generally not indicated in these patients, rare indications for surgical approaches indeed exist. We here report on our single-center experience with patients undergoing liver resection for FNH, focussing on preoperative diagnostic algorithms and quality of life (QoL) after surgery. METHODS: Medical records of 100 consecutive patients undergoing liver resection for FNH between 1992 and 2012 were retrospectively analyzed with regard to diagnostic pathways and indications for surgery. Quality of life (QoL) before and after surgery was evaluated using validated assessment tools. Student's t test, one-way ANOVA, χ (2), and binary logistic regression analyses such as Wilcoxon-Mann-Whitney test were used, as indicated. RESULTS: A combination of at least two preoperative diagnostic imaging approaches was applied in 99 cases, of which 70 patients were subjected to further imaging or tumor biopsy. In most patients, there was more than one indication for liver resection, including tumor-associated symptoms with abdominal discomfort (n = 46, 40.7 %), balance of risk for malignancy/history of cancer (n = 54, 47.8 %/n = 18; 33.3 %), tumor enlargement/jaundice of vascular and biliary structures (n = 13, 11.5 %), such as incidental findings during elective operation (n = 1, 0.9 %). Postoperative morbidity was 19 %, with serious complications (>grade 2, Clavien-Dindo classification) being evident in 8 %. Perioperative mortality was 0 %. Liver resection was associated with a significant overall improvement in general health (very good-excellent: preoperatively 47.4 % vs. postoperatively 68.1 %; p = 0.015). CONCLUSIONS: Liver resection remains a valuable therapeutic option in the treatment of either symptomatic FNH or if malignancy cannot finally be ruled out. If clinically indicated, liver resection for FNH represents a safe approach and may lead to significant improvements of QoL especially in symptomatic patients.

Bilateral elastofibroma dorsi: a case report of an uncommon and under-diagnosed tumor.

Elastofibroma dorsi is a rare benign tumor of the back, located between the latissimus dorsi and the rhomboid muscle. In most cases it is unilateral, but in up to 10% it occurs on both sides. The etiology is still in discussion. Here we report a case of a 51-year-old man with bilateral elastofibroma dorsi. The therapy of choice was surgical resection. No long-term complications were reported in a 6-month follow-up.

Liver resection in multimodal concepts improves survival of metastatic melanoma: a single-centre case-matched control study.

BACKGROUND/AIM: The aim of the present study was to define prognostic factors and to evaluate liver resection as an additive tool in metastatic melanoma. PATIENTS AND METHODS: In a case-control study, 32 patients with hepatic melanoma metastasis were analyzed between 1998-2012. Sixteen patients who underwent liver resection (6 patients with multimodal therapy) were matched to 16 patients scheduled for non-surgical approaches. Univariate and multivariate analyses were performed. RESULTS: Following primary resection and liver resection, respectively, survival was better for patients who underwent surgery in addition to multimodal therapy with 219 and 28 months, when compared to patients scheduled for non-surgical approaches with 64 (p=0.04) and 8 months (p=0.6). Following primary resection, primary tumor site, metastatic time <70 months, combination of multimodal therapy and surgery were of prognostic value (p<0.05). CONCLUSION: Liver resection should be considered a suitable additive tool in multimodal therapy of resectable metastatic melanoma.

Single-center experience using organs after rescue allocation for pancreas transplant in the eurotransplant region.

OBJECTIVES: Because of the shortage of available organs for transplants, graft allocation polices have been modified recently. This report deals with the effect of using organs after rescue allocation for pancreas transplant in a single center in the Eurotransplant Region to possibly expand the donor pool. MATERIALS AND METHODS: A retrospective analysis was performed. Between 2007 and 2010, thirty-one pancreas transplants were performed at the University Hospital of Leipzig, in Leipzig, Germany. Among these, 7 cases used rescue organs. These organs had been officially offered to, but rejected by, at least 3 consecutive transplant centers. Donor/recipient and clinical/laboratory transplant/posttransplant outcomes from patients receiving rescue organs were collected and were compared with organs from conventional donors. RESULTS: Mean donor age was greater in the rescue organ group than in the conventional donor group (28.3 ± 10.7 y vs 23.0 ± 12.5 y). During follow-up (2.3 ± 0.6 y rescue organ group vs 3.9 ± 1.2 y conventional donor group), patient, kidney, and pancreas graft survival rates were 85% in all 3 categories in the rescue organ group, whereas outcomes for conventional donors were 88%, 85%, and 83%. Incidences of pancreatic graft thrombosis, delayed graft function, acute and late rejection episodes (eg, perioperative complications) were comparable between groups. No differences existed between mean serum urea levels and mean HbA1c levels between groups 2 years after transplant. Whereas 2 years after surgery, mean serum creatinine levels (rescue organ group, 78.8 ± 21.0 µmol/L vs 114.3 ± 28.4 µmol/L in the conventional donor group) showed significant differences between groups. CONCLUSIONS: Results are promising. Further pro-spective studies are warranted to evaluate routine transplant of organs after rescue allocation.

Horseshoe kidney for transplantation: technical considerations.

Owing to the ongoing shortage of cadaver organs, kidneys with an atypical anatomy such as horseshoe kidneys must be considered for transplantation. Owing to its low prevalence, experience with the transplantation of a horseshoe kidney is very limited. This article reports on the transplantation of a horseshoe kidney to a 58-year-old man with renal failure from chronic glomerulonephritis. Because of a relatively thick isthmus, which indicated a complex urinary collecting and intrarenal vessel system, the kidney was transplanted en bloc. Together with optimal placement of the kidney, only adequate length and positioning of the vessels, especially the venous drainage, could prevent postoperative complications such as kinking of the vessels and thrombosis. These problems could be solved by cutting the renal veins without using a vena cava patch. Careful positioning of the kidney within the intraperitoneal cavity is also necessary. The decision to transplant the kidney en bloc or after separation depends on many factors and should be made individually.

Long-term outcome of conversion to sirolimus monotherapy after liver transplant.

OBJECTIVES: This study sought to assess the long-term efficacy and safety of conversion from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus monotherapy in liver transplant recipients with renal dysfunction. MATERIALS AND METHODS: Twenty-five liver transplant recipients with calcineurin inhibitor-based immunosuppression were included in this single-center, prospective study. Indications were renal dysfunction, avoidance of tumor recurrence, combination renal dysfunction and avoidance of tumor recurrence, and calcineurin inhibitor-related adverse effects. RESULTS: Mean interval between liver transplant and initiation of sirolimus monotherapy was 51.7 months. The mean follow-up was 75.6 months. The mean ± SD sirolimus whole-blood trough level was 9.0 ± 2.8 ng/mL after 6 months and 6.0 ± 1.8 ng/mL after 18 months. No rejection episodes occurred. There was an improvement of the mean creatinine level: 156.1 ± 54.9 µmol/L before conversion versus 129.1 ± 34.7 µmol/L approximately 3 years after conversion (P < .05). The glomerular filtration rate, measured by technetium Tc-99m-diethylenetriamine penta-acetic aerosol scintigraphy, improved from 27.4 ± 6.8 mL/min/1.73 m(2) before conversion to 43.3 ± 6.3 mL/min/1.73 m(2) at final follow-up. Proteinuria increased after conversion to sirolimus after 6 months (P < .05) and at last follow-up. The systolic blood pressure decreased from 151.5 ± 20.2 to 132.1 ± 19.4 mm Hg, and the diastolic from 89.7 ± 11.2 to 82.1 ± 9.1 mm Hg at last follow-up. Serum cholesterol and serum triglyceride levels were nearly unchanged. However, 50% of the patients were treated with lipid-lowering agents. Four patients had sirolimus-induced adverse effects (thrombocytopenia, gingival hyperplasia, oral ulceration). CONCLUSIONS: Conversion from calcineurin inhibitors to sirolimus monotherapy after liver transplant results in stabilization of renal function in 75% to 85% of cases and of blood pressure, without increased risk of rejection. The spectrum of adverse effects is low.

Renal autotransplantation--a possibility in the treatment of complex renal vascular diseases and ureteric injuries.

BACKGROUND: We report our contemporary experiences with renal autotransplantation in patients with complicated renal vascular diseases and/or complex ureteral injuries. Since its first performance, renal autotransplantation has been steadily improved and become a safe and effective procedure. MATERIAL/METHODS: Between 1998 and 2006, 6 renal autotransplantations in 6 patients were performed at the University Medical Center of Leipzig. After nephrectomy and renal perfusion ex vivo, the kidney was implanted standardized in the fossa iliaca. The vessels were anastomized to the iliac vessels, the ureter was reimplanted in an extravesical tunneled ureteroneocystostomy technique according to Lich-Gregoir. Demographic, clinical, and laboratory data of the patients were collected and analyzed for pre-, intra-, and postoperative period. RESULTS: Indications for renal autotransplantation were complex renovascular diseases in 2 patients (1 with fibromuscular dysplasia and 1 with Takayasu's arteritis) and in 4 patients with complex ureteral injuries. The median duration of follow-up was 9.7 years (range: 5.6-13.3). The laboratory values of our 6 patients showed improvements of creatinine, urea and blood pressure levels in comparison to the preoperative status at the end of follow-up period. CONCLUSIONS: The present study reports excellent results of renal autotransplantation in patients with renovascular disease or complex ureteric injuries. After a median follow-up of 9.7 years all 6 patients present with stable renal function as well as normal blood pressure values. Postoperative complications were observed with a rate comparable to other studies.

Blood lactate and pyruvate levels in the perioperative period of liver resection with Pringle maneuver.

INTRODUCTION: Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery, portal vein, and bile duct. This study aimed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection. METHODS: Twenty-five consecutive patients undergoing elective liver resection were prospectively randomized either to be treated with the Pringle maneuver (Pringle group, n = 14) or without clamping (Controls, n = 11). Blood lactate levels, pyruvate levels, and hepatic vein oxygen saturation were monitored perioperatively. RESULTS: Patients were comparable with respect to resection time, intraoperative blood loss, and duration of surgery. The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls (2.6 +/- 0.3 vs 1.8 +/- 0.2 mmol/l; p < 0.05). Further, the Pringle maneuver significantly increased hepatic venous lactate (3.3 +/- 0.3 vs 1.6 +/- 0.3 mmol/l; p < 0.05) and lactate/pyruvate ratio in hepatic venous blood (43 +/- 8 vs 21 +/- 5; p < 0.05) during surgery. This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group (61 +/- 4 vs 73 +/- 4%; p < 0.05). CONCLUSION: Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus. Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection.

Protective effects of early CD4(+) T cell reduction in hepatic ischemia/reperfusion injury.

AIM: CD4(+) T cells contribute to disturbances of liver microcirculation after warm ischemia/reperfusion (I/R). The aim of this study was to investigate a possible protective role of FTY720 (Sphingosine-1 phosphate receptor agonist) in this setting. MATERIAL AND METHODS: In an in vivo model (42 Wistar rats), ischemia of the left liver lobe was induced for 90 min under anesthesia with xylazine/ketanest. Sham-operated untreated ischemic and treatment group with FTY720 (1 mg/kg body weight intravenous) were investigated. The effect of FTY on I/R injury was assessed by in vivo microscopy 30-90 min after reperfusion (perfusion rate, vessel diameter, leukocyte-endothelial cell interactions, T cell infiltration), by measurement of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), reverse transcription-polymerase chain reaction (RT-PCR) of interleukin (IL)-2, IL-6, IL-10, TNF-alpha, toll-like receptor 4 (TLR-4), and by histological investigation. RESULTS: After 30 min of reperfusion, the number of T cells in sinusoids was increased four-fold. In the FTY group, the number of T cells was reduced to an half of the number of the ischemia group. Likewise, the number of adherent leukocytes in sinusoids (150.8 +/- 10.9% of s.o.) was reduced in the treatment group (117.3 +/- 12.2%; p < 0.05 vs ischemia), leading to an improvement in perfusion rate in this group (85.0 +/- 4.6% of sham group) compared to nontreated animals (57.5 +/- 10.8%; p < 0.05). According to improved microcirculation, AST/ALT values and histological tissue damage were reduced in the therapy group. RT-PCR revealed an increased expression of IL-2, IL-6, and TLR-4 in the nontreated ischemic group. This expression was clearly reduced in the treatment group. CONCLUSION: In conclusion, FTY720 ameliorates the microcirculatory, biochemical, and histological manifestations of hepatic I/R injury by preventing T cell infiltration. These results indicate that T cells are pivotal mediators in hepatic I/R and may have important implications early after liver transplantation and in warm ischemia.

Pathophysiological role of platelets and platelet system in acute pancreatitis.

The most successful approach for restoring normal long-term glucose homeostasis in type I diabetes mellitus is whole-organ pancreas transplantation. Graft pancreatitis is observed in up to 20% of patients and may lead to loss of the transplanted organ. Several pathophysiological events have been implicated in this form of pancreatitis. The most important cause of early graft pancreatitis is ischemia/reperfusion (I/R)-related disturbance of microvascular perfusion with subsequent hypoxic tissue damage. Recently, considerable evidence accumulated that, among a variety of other pathophysiological events, the activation of platelets can contribute to I/R injury in the course of acute pancreatitis experimentally and clinically. This review summarizes the events affecting platelet function and, therefore, pancreatic microcirculation leading to acute pancreatitis. Therapeutic approaches and own results are presented.

Pathophysiological role of platelets in acute experimental pancreatitis: influence of endothelin A receptor blockade.

The potential pathophysiological role of platelet-endothelium interactions was investigated during ischemia/reperfusion (I/R), and the effect of a selective endothelin(A) receptor antagonist (ET(A)-RA) was evaluated in an acute pancreatitis model. Acute pancreatitis was induced by warm ischemia (60 min) in Wistar rats, and its effects with and without antagonist treatment were investigated. Equivalent sham-operated animals were also studied. Microcirculatory changes were assessed by in vivo microscopy, and serum levels for lipase/amylase and histological specimens were investigated. Capillary constriction to 83.7 +/- 6.7% of sham-operated diameters was observed after 60 min of ischemia. A capillary density of 56.8 +/- 9.3% of the sham-operated group (396.3 +/- 15.8 mm(-1)) was measured after reperfusion. Stagnant leukocytes (329.5 +/- 30.4%) and platelets (337.5 +/- 32.3%) increased in postcapillary venules (P < 0.05). Administration of the ET(A)-RA significantly reduced I/R injury. Capillary diameters were maintained (101.4 +/- 4.5%), and capillary density was improved to 73.3 +/- 7.6% of sham-operated animals (P < 0.05). Stagnant leukocytes (152.3 +/- 10.6%) and platelets (207.1 +/- 19.8%) in sinusoids and postcapillary venules were reduced (P < 0.05). The extent of acute pancreatitis was reduced in the therapy group as indicated by serum lipase/amylase values and histological tissue damage (P < 0.05). Thus, ET(A)-RA therapy was effective in reducing I/R-induced pancreatitis in this experimental model.

Management and outcome in patients with Klatskin-mimicking lesions of the biliary tree.

The preoperative and even intraoperative differentiation between benign and malignant strictures at the hepatic hilum remains difficult. The aim of this study was to assess clinical, radiologic, intraoperative, and histopathologic findings; surgical treatment; and outcome of patients with Klatskin mimicking benign lesions. Of 49 consecutive patients who were operated on the initial preoperative radiologic diagnosis of hilar adenocarcinoma (Klatskin tumor), 7 (14%) had benign conditions after final histopathologic diagnosis. Pretreatment work-up, therapy, and outcome of these patients were analyzed. Based on preoperative clinical symptoms, imaging assessment, and CA19-9 values, all seven patients were classified as having malignant neoplasms. At laparotomy, the tumors of six patients were judged to be malignant. Five patients underwent hilar resection and concomitant liver resection, and two patients underwent hilar resection alone. There were no operative deaths. The definitive histopathologic examination showed severe cholangitis with extensive periductal fibrosis in all patients. After a median follow-up of 32 months, all patients are well. Clinical presentation and imaging assessment were similar for Klatskin tumors and benign fibrosing disease; therefore, an aggressive resectional approach is justified in any patient with suspicious obstruction of the liver hilum.

Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection.

OBJECTIVE: First, to analyze the strategy for 184 patients with hilar cholangiocarcinoma seen and treated at a single interdisciplinary hepatobiliary center during a 10-year period. Second, to compare long-term outcome in patients undergoing surgical or palliative treatment, and third to evaluate the role of photodynamic therapy in this concept. SUMMARY BACKGROUND DATA: Tumor resection is attainable in a minority of patients (<30%). When resection is not possible, radiotherapy and/or chemotherapy have been found to be an ineffective palliative option. Recently, photodynamic therapy (PDT) has been evaluated as a palliative and neoadjuvant modality. METHODS: Treatment and outcome data of 184 patients with hilar cholangiocarcinoma were analyzed prospectively between 1994 and 2004. Sixty patients underwent resection (8 after neoadjuvant PDT); 68 had PDT in addition to stenting and 56 had stenting alone. RESULTS: The 30-day death rate after resection was 8.3%. Major complications occurred in 52%. The overall 1-, 3-, and 5-year survival rates were 69%, 30%, and 22%, respectively. R0, R1, and R2 resection resulted in 5-year survival rates of 27%, 10%, and 0%, respectively. Multivariate analysis identified R0 resection (P < 0.01), grading (P < 0.05), and on the limit to significance venous invasion (P = 0.06) as independent prognostic factors for survival. PDT and stenting resulted in longer median survival (12 vs. 6.4 months, P < 0.01), lower serum bilirubin levels (P < 0.05), and higher Karnofsky performance status (P < 0.01) as compared with stenting alone. Median survival after PDT and stenting, but not after stenting alone, did not differ from that after both R1 and R2 resection. CONCLUSION: Only complete tumor resection, including hepatic resection, enables long-term survival for patients with hilar cholangiocarcinoma. Palliative PDT and subsequent stenting resulted in longer survival than stenting alone and has a similar survival time compared with incomplete R1 and R2 resection. However, these improvements in palliative treatment by PDT will not change the concept of an aggressive resectional approach.

Clazosentan (Actelion).

Clazosentan, an endothelin ETA antagonist, is under development by Actelion (formerly Axovan), under license from F Hoffman-La Roche, for the potential prevention of cerebral infarction and ischemia induced by cerebral vasospasm following subarachnoid hemorrhage. Results from the phase IIb portion of a phase IIb/III clinical study are expected in the first half of 2006.

Attenuation of proinflammatory gene expression and microcirculatory disturbances by endothelin A receptor blockade after orthotopic liver transplantation in pigs.

BACKGROUND: Endothelin-1 (ET-1), a very potent mediator of vasoconstriction, leads to microcirculatory disturbances and release of proinflammatory cytokines under pathophysiologic conditions. Our aim was to evaluate the effect of a selective ET(A)-receptor antagonist (ET(A)-RA) on cold ischemia/reperfusion (I/R) injury in a pig model. METHODS: Twenty pigs revealed orthotopic liver transplantation. The animals were randomized into 2 groups: control pigs received isotonic saline; the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were re-laparotomized to obtain tissue specimens. Liver tissue samples were collected and quantitative mRNA expression for prepro-ET-1, ET(A) receptor, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, and endothelial nitric oxide synthase was analyzed using the TaqMan system. Additionally, immunohistochemical analysis for ET-1 was performed. Hepatic microcirculation was evaluated by laser Doppler flow measurement and partial pressure of oxygen and carbon dioxide measurements with the Paratrend sensor. Postischemic liver damage was monitored by measurement of liver enzymes and by histologic analysis using a semiquantitative scoring classification. RESULTS: Treatment with the ET(A)-RA significantly reduced the severity of I/R injury evidenced by lower serum AST, ALT and GLDH. Analysis of partial pressure of oxygen and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with a relevant reduction of tissue injury. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, ET(A) receptor, endothelial nitric oxide synthase, pro-TNF-alpha, pro-IL-1beta and pro-IL-6 in the therapy group. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Histologic investigation suggested less tissue damage in treated animals. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after liver transplantation. ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6.

Effects of ET(A) receptor antagonism on proinflammatory gene expression and microcirculation following hepatic ischemia/reperfusion.

BACKGROUND: The objective of this study was to investigate the effect of a specific endothelin(A) receptor antagonist (ET(A)-RA) on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines and on the microhemodynamics (assessed by measurement of laser Doppler flow and tissue blood gases) following complete vascular exclusion of the porcine liver. STUDY DESIGN: Sixteen adult German landrace pigs were subjected to 120 min of warm hepatic ischemia by total vascular exclusion. To avoid portal congestion, a passive porto-femoro/jugular bypass was implanted. The animals were divided into 2 groups: the control group received saline solution and the therapy group was given the selective ET(A)-RA BSF 208075. Hepatic microcirculation was evaluated by p(O(2)) and p(CO(2)) measurement with the Paratrend sensor and by laser Doppler flow measurement. Liver tissue samples were collected 1 h after reperfusion and quantitative mRNA expression for prepro-ET-1, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, eNOS was analyzed using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for ET-1 was performed. Postischemic liver damage was monitored by measurement of liver enzymes and assessed by histological analysis using a semiquantitative scoring classification. RESULTS: Partial oxygen pressure in the hepatic tissue and laser Doppler flow were significantly improved in the therapy group. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, eNOS, pro-TNF-alpha, and pro-IL-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Furthermore, blockade of ET(A) receptors prevents tissue damage. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after 120 min liver ischemia and reperfusion. The authors were able to show that ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha and IL-6.