Randomized controlled multicenter trial on the effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound fibrin sealant during liver resection (ESSCALIVER study, NCT00918619).

BACKGROUND: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection. METHODS: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period. RESULTS: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [-6.0 %, 19.8 %] does not include the lower noninferiority margin (-10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups. CONCLUSION: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.

[Hepatic peliosis--a rare liver tumor and challenge for diagnostic investigation plus therapy]. / Peliosis hepatis: seltene Differenzialdiagnose der Leberraumforderung und interdisziplinäre Herausforderung für Diagnostik und Therapie.

HISTORY AND ADMISSION FINDINGS: A 42-year-old woman presented at our hospital, because of a non-specific hepatic tumor. She complained of dull pain in the right upper abdomen. Physical examination did not reveal any pathology, especially there was no evidence of an infection. Abuse of drugs, alcohol or anticontraceptives was also denied. INVESTIGATIONS UND THERAPY: Even though fine needle biopsy and extensive radiological examination were performed a malignant nature of the liver tumor could not be excluded. Therefore a hemihepatectomy was performed. TREATMENT AND COURSE: The postoperative course was normal and the patient was released from hospital after 11 days. The histological examination revealed an incidental finding of an extended peliosis hepatis. CONCLUSION: Peliosis hepatis is a rare disease of the liver, histologically characterized by blood filled cavities. The clinical picture of this disease is mostly asymptomatic, but it may also lead to liver failure, portal hypertention and massive intrahepatic bleeding. The preoperative differentiation is an interdisciplinary challenge, especially in terms of radiological examination (chemical shift MRI; liver specific radiocontrast). If the distinction to a malignancy cannot be excluded operative resection is indicated.

[Rare cause of acute liver failure]. / Seltene Ursache eines akuten Leberversagens.

A rare cause of acute liver failure is adult onset Still's disease (AOSD), a systemic inflammatory disorder. We present the case of a 24-year-old woman who presented with acute liver failure necessitating high urgency liver transplantation. The diagnosis of AOSD was established in accordance with the Yamaguchi classification criteria, including arthralgia, fever, sore throat, rash and hepatosplenomegaly. The early detection and therapy of AOSD can possibly avoid the development of liver failure with a poor prognosis.

Xenon anesthesia for liver transplant surgery: a report of four cases.

It is well established that patients presenting for orthotopic liver transplantation pose challenging surgical and anesthesiological problems. Intraoperatively, severe hemodynamic instability due to profuse bleeding and acute cardiomyopathy during reperfusion are major concerns. In addition, ischemia-reperfusion injury can compromise postoperative graft function. Xenon, with its potential to maintain hemodynamic stability, preserve cardiac function, and protect the liver graft of the recipient, seems to be a promising anesthetic agent for liver transplant surgery. To date, xenon has not been used as an anesthetic in liver transplantations. We therefore have reported our initial experience with four patients who underwent orthotopic deceased donor liver transplantation under xenon anesthesia. Although all patients had advanced liver disease and experienced significant intraoperative bleeding, their intraoperative courses, including reperfusion, under xenon anesthesia were remarkably stable. The patients required only moderate, temporary catecholamine support, which was withdrawn at the end of the surgery. Xenon anesthesia for liver transplant procedures proved to be feasible. Immediate postoperative organ function was satisfactory in all patients.

Can the preprocurement pancreas suitability score predict ischemia-reperfusion injury and graft survival after pancreas transplantation?

BACKGROUND: Ischemia-reperfusion injury (IRI) is common after pancreas transplantation, leading to pancreatitis or thrombosis with the need for relaparotomy or even graft loss. Optimal donor selection may reduce the postoperative morbidity of IRI. The Eurotransplant preprocurement pancreas suitability score (P-PASS) seeks to identify ideal donors with a value <17. Owing to the organ shortage the waiting time for pancreas transplantation is increasing, a problem that may be addressed with the use of extended-criteria donors. We analyzed our pancreas transplantations regarding postoperative complications according to the P-PASS. To reflect IRI we used the peak C-reactive protein (CRP) levels during the first 3 postoperative days. METHODS: From January 2009 to July 2010, we transplanted 52 pancreas grafts, including, 50 simultaneous pancreas-kidney transplantations (SPK), 1 after a kidney graft, and 1 alone. For 3 SPK donors the P-PASS was not available. All transplantations were performed using systemic venous and enteric drainage. The immunosuppression protocol included antibody induction with antithymocyte globulin and maintenance therapy with steroids, tacrolimus, and mycophenolate mofetil. The peak CRP in the first 3 postoperative days was used as a marker for IRI. RESULTS: The mean P-PASS of our donors was 16.4 ± 2.6 (range, 12-22). We compared 24 patients receiving organs from "ideal" donors (P-PASS <17; ID) with 25 receiving grafts from extended-criteria donors (P-PASS ≥17; ED). There was no significant difference in the incidence of graft loss among ID versus ED grafts (20.8% vs 20.0%; P = 1.0). Comparing the rates of postoperative complications of patients, we did not observe a significant difference in graft thrombosis (4.2% vs 16.0%; P = .349), relaparotomy (29.2% vs 40.0%; P = .551), a pancreatic fistula (37.5% vs 28.0%; P = .543), or the length of hospital stay (36.5 ± 19.2 vs 37.4 ± 20.8 days; P = .875), respectively. Regarding IRI, there was no significant difference in peak CRP values (14.1 ± 5.5 vs 16.2 ± 6.0 mg/dL; P = .211). CONCLUSION: This single center analysis failed to show that P-PASS significantly predicted pancreas graft survival, postoperative morbidity, or IRI severity. These findings suggested a chance to increase the donor pool using extended-criteria donors.

Incidence and treatment of pancreatic fistula after simultaneous pancreas kidney transplantation.

BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) is associated with great postoperative morbidity, including the need for relaparotomy in up to 40% of cases. Because the pancreatic graft is known to be the major cause of the high morbidity, we examined the incidence and treatment of pancreatic fistula (PF) in this retrospective analysis. METHODS: From January 2004 to July 2010, we transplanted 52 pancreas grafts, including 50 SPK, 1 pancreas after kidney, and 1 pancreas transplantation alone. There were 22 female and 30 male patients with an overall mean age of 42.4 ± 7.4 years. The mean duration of diabetes was 27.3 + 8.1 years, mean duration of dialysis was 24.2 ± 28.6 months, and 14 cases were pre-emptive transplantations. All procedures were performed using systemic venous and enteric drainage. RESULTS: The incidence of clinically relevant PF was 16/52 (30.8%), including 11 (68.8%) that were treated conservatively with a drain. Five patients (31.2%) needed relaparotomy: 2 due to enteric leakage, 2 due to acute abdominal pain with graft pancreatitis observed at laparotomy, and 1 due to acute hemorrhage. In 3 cases, graft pancreatectomy was necessary. Comparing the patients with (PF+) versus without (PF-) fistulas, there was no significant difference in cold ischemia time (10.9 ± 2.6 hours vs 10.4 ± 4.4 hours; P = .633), donor age. We found a significantly higher peak C-reactive protein (CRP) level in the patients with pancreatic fistula (3661.4 ± 3474.8 U/L vs 821.8 ± 1293.7 U/L, P = .022). The lipase concentration measured in the drainage fluid postoperatively showed a significant difference between the 2 groups (3661.4 ± 3474.8 U/L vs 821.8 ± 1293.7 U/L; P = 0.006). Also, the amylase concentration was higher in the PF+ group (1747.3 ± 3346.7 U/L vs 265.3 ± 254.9 U/L; P = .097). Graft loss occurred in 4/16 cases (25.0%) of PF+ and 7/36 (19.4%) of PF- (P = .719). CONCLUSION: The incidence of PF after pancreas transplantation is high and seems to be associated with ischemia-reperfusion injury reflected by peak-CRP. In most cases a conservative treatment is successful. The occurrence of a PF does not significantly impair graft survival.

[Prediction of perioperative mortality in patients with advanced liver disease and abdominal surgery by the use of different scoring systems and tests]. / Prädiktion der perioperativen Mortalität bei Patienten mit fortgeschrittener Lebererkrankung und abdominalchirurgischen Eingriffen anhand unterschiedlicher Score- und Testsysteme.

Patients with advanced liver disease show increased morbidity and mortality after hepatic resection and non-hepatic digestive surgery. Furthermore, postoperative liver failure is associated with a poor outcome, representing an important clinical problem. For evaluation of the perioperative mortality and the hepatic function, several scoring systems, clinical parameters, and static and dynamic tests are available. Recently, the Model for End-Stage Liver Disease (MELD) has been shown to provide a complementary predictive value to the widely used Child Turcotte Pugh score. Patients with Child Turcotte Pugh class C cirrhosis and MELD scores >14 are generally not considered for surgical intervention. Patients with Child Turcotte Pugh class B cirrhosis and MELD scores >8-14 have an increased perioperative risk and the indication for surgery should be assessed carefully. In patients with Child Turcotte Pugh class A cirrhosis and MELD scores of

[The solid pseudopapillary tumor (SPT)--a rare neoplasm of the pancreas]. / Der solid pseudopapilläre Pankreastumor (SPT)--eine seltene Raumforderung der Bauchspeicheldrüse.

BACKGROUND: In general, the rare SPT is a tumour of low malignancy predominantly affecting young women. The outcome after radical resection is favourable. In exceptional cases the tumour presents as solid pseudopapillary carcinoma (SPC) with typical malignant features and even metastases. Unresectable liver metastases can be treated with RFA, TACE or chemotherapy. METHODS: We retrospectively reviewed the surgical approach, immunohistochemistry and clinical outcome in five female patients (1998--2007). RESULTS: The mean age was 16 years (range: 13-47 years). For radical tumour removal a pancreato-duodenectomy (n = 3), a distal pancreatectomy (n = 1) and an enucleation (n = 1) were performed. We encountered a mean tumour diameter of 8 cm (range: 6-15 cm), an angioinvasion (3/5) and a lymphatic infiltration (1/5). After 30 to 101 months follow-up four patients were free of recurrence. Chemotherapy has resulted in a survival of over 98 months in a case of SPC with liver metastases. CONCLUSION: SPT is a tumour of low malignancy. Radical resection is recommended for long-term recurrence-free survival. Chemotherapy may prolong survival in SPC with unresectable metastases.

[Hepatic angiomyolipoma--a rare liver tumor]. / Das Angiomyolipom der Leber--eine seltene Differenzialdiagnose der Leberraumforderung.

A 22-year-old woman was treated for a hepatic lesion with a high suspicion of a liver adenoma at another hospital. The patient presented with unspecific abdominal pain. Further physical examination was unremarkable. A biopsy of the liver lesion revealed hepatic adenoma. Because of the increasing tumour size over a one-year period the patient was referred to our department for surgical therapy. On MRI scan, the liver mass measured 10 x 9 x 9 cm in the right liver lobe with contact to the right hilum. Because of the histological signs of adenoma a right hepatic lobectomy was performed. Postoperative follow-up was uneventful. The pathological diagnosis of hepatic angiomyolipoma was obtained. Angiomyolipoma of the liver is a rare benign mesenchymal tumour often mimicking other hepatic lesions. Histological features are thick-walled blood vessels, mature fat and smooth muscle in various proportions. The biological behaviour of the tumour is benign, although distant metastases are occasionally possible. Due to the potential for malignant transformation, tumour resection should be performed.

Tacrolimus monotherapy without steroids after liver transplantation--a prospective randomized double-blinded placebo-controlled trial.

Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.

Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma.

Tumor recurrence is a major problem after orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). In 60 patients OLT was performed for HCC after pretreatment by repeated transarterial chemoembolization (TACE). Forty-four recipients exceeded the Milan criteria. Recurrence-free 5-year survival was 65.2% and 5-year freedom from recurrence was 73.2%. During the waiting time, 14 patients experienced minimal change, which did not fulfill the definition of tumor progression according to official oncological criteria. Five-year freedom from recurrence among patients with stable compared with progressive disease was 93.3% versus 28.1%, respectively (P = .0001). A strict TACE pretreatment protocol may select patients with obviously biologically less aggressive tumors, who are suitable for OLT even if the HCC exceeds the commonly accepted listing criteria.

Flow and pressure during liver preservation under ex situ and in situ perfusion with University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution.

Effective preservation of liver grafts is the first essential step for successful liver transplantation. Insufficient perfusion leads to ischemic-type biliary lesions after transplantation. Perfusion of the graft can be performed either in situ or ex situ, with gravity flow or pressure-controlled. Mainly University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are used widespread in clinical liver transplantation. Due to a persistent lack of data, we performed this systematic investigation of in situ and ex situ perfusion of liver grafts with HTK (low-viscous) and UW (high-viscous) solutions at different pressure steps on the perfusion solution (gravity flow, 50, 100, 150, and 200 mm Hg). End points were perfusion flow and pressure in the hepatic artery. A pig model was used with n = 8 pigs randomized to each (HTK and UW) group. In situ perfusion was ineffective for both solutions at any pressure on the perfusate bag. Ex situ perfusion showed significantly improved flow and pressure in the hepatic artery and, therefore, was highly effective. No major differences between HTK and UW solutions could be detected. Therefore, an additional ex situ perfusion of the hepatic artery should be mandatory in every liver procurement.

[Single center experience over a 5-year period with sequential transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC)]. / Sequentielle transarterielle Chemoembolisation (TACE) des hepatozellulären Karzinoms (HCC)--Erfahrungsbericht eines einzelnen Zentrums über 5 Jahre.

PURPOSE: To analyze the course of disease of patients treated with sequential TACE and to evaluate the dependent and independent prognostic factors for patient survival using the Cox Proportional Hazard Model. MATERIALS AND METHODS: 94 patients palliatively treated with TACE. Patients were selected if they had been treated at least 3 times. The TACE procedure was carried out at 8-week intervals using a suspension consisting of a fixed dosage of Mitomycin C (10 mg) and 10 ml Lipiodol. Follow-up investigations included contrast-enhanced multislice CT before and after TACE and assessment of the laboratory test results (i. e., blood count, liver enzymes, and coagulation). RESULTS: In 66.7 % of the patients, multifocal tumors were found. In 16.0 % of the patients, the tumor load represented more then 50 % of the liver volume. In 23.4 % of the cases, a portal vein thrombosis was found in the initial CT scan. The mean survival for the total cohort was 24.1 months (95 %-CI 20.1 - 28.2). During the investigation period, 72/94 of the patients died. The cumulative 1-year, 2-year, and 3-year survival rates are 71.6 %, 33.9 %, und 17.2 %, respectively. A median of 6.0 +/- 3.1 (range 14, n total = 612 TACE) was performed in each patient. A total of 62.5 % patients died because of tumor progression whereas 18.1 % died due to progressive liver failure. Patients in whom the tumor responded to the TACE treatment and who did not develop ascites or those with Okuda stage I or unifocal tumor growth showed a survival benefit whereas the presence of portal vein thrombosis was associated with a significantly poor outcome (p < 0.05). The Child-Pugh stage was not statistically significant for the disease course; the occurrence of new tumor lesions had no influence with regard to 1-year and 2-year survival but had a significant influence on long-term survival (p < 0.05). Independent prognostic factors are (multivariate analysis; p < 0.05): number of TACE performed, tumor type (i. e., unifocal vs. multifocal), response to TACE (response vs. progression), and Okuda stage. CONCLUSION: Our results emphasize the value of TACE in the palliative treatment of HCC. Under sequential TACE therapy the course of disease in patients suffering from portal vein thrombosis was not significantly worse. Crucial prognostic factors for the course of the HCC are tumor type and extension, response to TACE, and liver function at the beginning of TACE.

Ischemic type biliary lesions in histidine-tryptophan-ketoglutarate (HTK) preserved liver grafts.

Ischemic type biliary lesions lead to considerable morbidity following orthotopic liver transplantation. The exact pathogenesis is unknown. One major hypothesis is that insufficient perfusion of the arterial vessels of the biliary tree, especially under perfusion with the high viscous University of Wisconsin solution, might be responsible for ischemic type biliary lesions. Due to low viscosity, HTK solution is reported to have a lower incidence of biliary complications. However, there is no data concerning ischemic type biliary lesions in HTK preserved livers. In this paper we report our results after orthotopic liver transplantation with special regard to ischemic type biliary lesions in liver grafts preserved with HTK solution. Between 09/1997 and 01/2005 300 liver transplantations were performed in our center. Thirty-two (10.7%) liver grafts were preserved with HTK solution, 268 (89.3%) were preserved with UW solution. Six and 43 grafts showed ischemic type biliary lesions after orthotopic liver transplantation in HTK- (18.8%) and UW- (16.0%) groups, respectively (p=0.696). There was no statistical significant difference between the two groups. Donor related factors, recipient age, indication for transplantation, transplantation technique, immunosuppression and ischemia time were comparable in both groups. Ischemic type biliary lesions occurred with the same frequency in HTK preserved livers compared to UW preserved organs. We suggest that low viscosity of the preservation fluid by itself does not guarantee reliable perfusion of the small arteries of a liver graft and a pressure perfusion might be beneficial even in HTK solution.

[Arterial back table pressure perfusion prevents ischemic biliary lesions after orthotopic liver transplantation]. / Arterielle Ex-situ-Nachperfusion unter Druck zur Vermeidung von "Ischemic Type Biliary Lesions" nach orthotoper Lebertransplantation.

INTRODUCTION: Ischemic biliary lesions are a threatening complication following orthotopic liver transplantation. Their exact pathophysiological mechanism is unknown so far, but insufficient perfusion of biliary arterial vessels might be responsible for the development of these lesions. This might be changed by improved perfusion techniques. We performed a controlled study of cases since February 2000. MATERIALS AND METHODS: We used arterial back table pressure perfusion to achieve reliable perfusion of the capillary system of the biliary tract, which may be impaired by the high viscosity of University of Wisconsin solution. In this study, 190 orthotopic liver transplantations performed between September 1997 and July 2002 were investigated with regard to ischemic biliary lesions. RESULTS: One hundred thirty-one grafts were preserved by in situ standard perfusion including portal perfusion,whereas additional arterial back table pressure perfusion was performed in 59 cases. Donor-related factors, recipient age, indications for transplantation, transplantation techniques, and ischemia times were comparable between groups. Twenty-one (16%) of the patients in the standard perfusion group and only one of the those receiving arterial back table pressure perfusion developed ischemic biliary lesions. This difference was highly significant (P=0.004). Maximal aspartate aminotransferase and alanine aminotransferase levels in the first 3 days were significantly lower in the arterial back table pressure perfusion group (P>0.05). CONCLUSION: Arterial back table pressure perfusion is an easy and reliable method for preventing ischemic biliary lesions in orthotopic liver transplantation. It should, therefore, be the standard technique in liver procurement.

The role of monocyte chemoattractant protein-1 in orthotopic liver transplantation.

Hepatic ischemia reperfusion injury as well as acute graft rejection (RE) after orthotopic liver transplantation (OLT) are associated with leukocyte invasion of the graft. Local synthesis of chemokines is a key reaction in the recruitment and activation of inflammatory leukocytes and consequent liver damage. In this paper we describe the role of monocyte chemoattractant protein (MCP)-1 (CCL2) in human OLT. We investigated the serum CC-chemokine levels for MCP-1 by specific ELISAs after OLT in 105 human liver allografts between September 1997 and January 2001. One hour after reperfusion we saw a significant (t test) increase of MCP-1 in peripheral blood (92.5 +/- 85.8 pg/mL to 774.2 +/- 319.6 pg/mL, 8.3-fold, P <.0001), hepatic venous blood (92.5 +/- 85.8 pg/mL to 866.7 +/- 376.1 pg/mL, 9.3-fold, P <.0001), and portal venous blood (92.5 +/- 85.8 pg/mL to 792.9 +/- 408.0 pg/mL, 8.5-fold, P < 0.0001) during hepatic ischemia reperfusion injury. An analysis of the correlation (Spearman's test, rs) between the expression of MCP-1 and the AST (rs 0.555, P <.025) and ALT (rs 0.852, P <.0001) showed a significant linear correlation. During RE a significant (t test) increase of MCP-1 (125.5 +/- 95.6 pg/mL to 188.5 +/- 124.6 pg/mL, 3.86-fold, P <.0001) was demonstrated. The successful treatment of the RE led again to a decline to lower base levels. Hepatic ischemia reperfusion syndrome as well as RE after OLT are characterized by typical patterns of CCL-2 overexpression. This finding proposes a new noninvasive, early diagnostic test after OLT.