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BACKGROUND: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. MATERIAL AND METHODS: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT. RESULTS: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early ( 3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. CONCLUSIONS: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

Background and Aim: Chemoresistance often leads to loss of the last treatment option for cancer. 2-Methoxyestradiol (2-ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2-ME2 on multidrug-resistant human cells from pancreatic and gastric cancer. Methods: We investigated the impact of 2-ME2 on multidrug-resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1-gene. Results: In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1-negative and 87% in MDR1-positive cells after 1 μmol/L 2-ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1-positive and 95% in MDR1-negative cells. Strong induction of apoptosis was induced after a low dose of 2-ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug-resistant cells of both tumor types. The number of apoptotic cells after 2-ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1-negative gastric cancer cells. Conclusion: 2-ME2 may therefore have clinical application for chemoresistant cancer.

Compared to primary liver transplantation (LT), the inferior results in the outcome of liver retransplantation (re-LT) continue to be a major challenge. The purpose of this study was to analyze changes in and outcomes of re-LT over a period of 15 years at the Charite Virchow Clinic. Between 1989 and 2003, we performed 1,619 LTs and 157 re-LTs (9.7%) in 1,462 patients. A total of 119 retransplants (50 females, 69 males) were analyzed after consideration of exclusion criteria: recipient age

Background: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. Methods: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as ‘MMF-free’ control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. Results: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and Cmax of MPA increased in combination with tacrolimus compared with cyclosporine. Conclusions: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Mit dem Begriff malignes epitheloides Hamangioendotheliom wird ein seltener vaskularer Tumor, der hauptsachlich im Weichgewebe, der Lunge und der Leber beschrieben worden ist, bezeichnet. Da die Verlaufe mit und ohne Therapie sehr variabel sind, berichten wir hier unsere Erfahrungen mit der resektiven Therapie und der Lebertransplantation fur diesen seltenen Lebertumor. Wir beobachteten 7 Patienten in einem Zeitraum von 5 Jahren mit der histologischen Diagnose eines hepatischen epitheloiden Hamangioendothelioms. Die Leberveranderungen wurden in 5 von 7 Fallen zufallig bemerkt und die Patientenverlaufe prospektiv beobachtet. Therapie und Verlauf wurden in Form von Fallberichten dargestellt. Drei Patienten wurden mit einer formalen Leberteilresektion versorgt und je ein Patient erhielt ein Lebendspende-Teillebertransplantat und ein komplettes Lebertransplantat. Ein Patient befindet sich zz. auf der Warteliste zur Transplantation und bei einer Patientin ist der Tumorstatus unter alternativen Heilmethoden zz. stationar. Alle Patienten erholten sich gut vom operativen Eingriff, sind 2 Monate bis 4 Jahre nach der Operation beschwerdefrei und zeigen keinen Anhalt fur ein Tumorrezidiv. Die formale Leberteilresektion oder bei diffusem Befall die orthotope Lebertransplantation zeigen gute Ergebnisse beim hepatischen, malignen, epitheloiden Hamangioendotheliom. Daher wird die Resektion als Therapie der Wahl fur diese Erkrankung vorgeschlagen.

Improvements in the Field of Liver Transplantation Liver transplantation is the most effective therapy in patients with end-stage liver disease or acute failure. By improvements in

Objectives: To use particle image velocimetry (PIV) to study the haemodynamics and shear stress associated with cuffed and straight PTFE-venous anastomoses. Methods: Silastic models of a straight and cuffed (Venaflo™) PTFE-venous anastomoses were attached to a pulsatile flow ‘Berlin Heart’ circuit filled with glycerine/water and hollow glass tracer spheres. Instantaneous velocity fields were obtained PIV and shear rates and patterns calculated from frame-by-frame analysis. Results: A high velocity jet struck the anastomotic ‘floor’ and was deflected toward the venous outflow. Shear stresses near the floor were significantly higher, in the straight anastomosis. Sites of high shear stress correlated well with the known sites of intimal hyperplasia. Conclusions: A cuffed anastomosis type may be favourable in terms of local haemodynamics so enhancing the long-term patency of PTFE-venous grafts.

Mesenterialarterienverschlusse sind eine seltene Komplikation der Thrombangiitis obliterans. Wir berichten uber einen 30-jahrigen Patienten mit einer Thrombangiitis obliterans und einem Mesenterialarterienverschluss als Komplikation dieser Erkrankung. Bei unklaren abdominellen Schmerzen wurden im Rahmen einer Laparoskopie ein Dunndarminfarkt und eine Minderperfusion der Leber bei dem Patienten diagnostiziert, sodass zunachst eine Dunndarmteilresektion durchgefuhrt werden musste. Bei weiterhin bestehender Dunndarmischamie erfolgte dann eine Angiographie, die einen zentralen Verschluss des Truncus coeliacus und der A. mesenterica superior zeigte. Daraufhin wurde der Pat. relaparotomiert, die A. mesenterica superior embolektomiert, ein Venenbypass von der A. mesenterica superior zu beiden Leberarterien gelegt und eine erneute Dunndarmteilresektion durchgefuhrt. Nach initial unauffalligem Verlauf und Entlassung wurde der Patient bei erneuter abdomineller Symptomatik 3 Wochen spater wieder stationar aufgenommen und aufgrund eines akuten Verschlusses der A. colica dextra eine Hemikolektomie rechts durchgefuhrt. Seit einem Jahr ist bei dem Patienten keine abdominelle Symptomatik im Rahmen seiner Erkrankung mehr aufgetreten.

Objectives: to evaluate the influence of intraoperative arterial prostaglandin E1(alprostadil) infusion on hydraulic impedance in relation to graft patency. Methods: hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 μg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Zx) and characteristic (Z0) impedances as well as phase relations were derived and related to graft outcome after three years. Results: significant changes after administration of prostaglandin were observed for overall pressure (74 vs 84 mmHg, p

Background . Measurements of intramyocardial impedance at high frequencies can indicate alterations in cell membranes and intracellular spaces during acute cardiac allograft rejection. Methods . Fifteen beagle dogs underwent heterotopic heart transplantation and were immunosuppressed with cyclosporine and methyl prednisolone (MP). Impedance was determined twice daily by means of four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intramyocardial electrogram (IMEG) were performed as reference methods. A total of 23 rejection episodes were induced. When acute rejection was recognized histologically and through IMEG readings, the animals were treated with a bolus of 125 mg of methyl prednisolone over 5 consecutive days. Treatment of rejection was controlled by biopsy and IMEG. Results . All hearts showed a uniform decrease in impedance of about 28.3% ± 5.5% immediately after transplantation, which subsequently reached a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grades 1A to 1B (ISHLT) were accompanied by a statistically significant increase in impedance of 12.2% ± 2.5%; of grades 2 to 3A of 19.2% ± 3.2% and of grades 3B to 4 of 27.0% ± 2.9%. Sensitivity was 96%, specificity 91%. Successful treatment of rejection led to a decrease of impedance to the initial levels. Conclusions . The amount of increase in impedance of high frequencies is a method to stratify acute cardiac allograft rejection into grades like histologically grading. The effectiveness of rejection treatment can also be monitored through impedance measurement. The method is also applicable for telemetric rejection monitoring by means of an implantable device.

12 beagle dogs underwent neck-heart transplantation and were immunosuppressed with cyclosporine and methylprednisolone. Intramyocardial impedance was determined twice daily with four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intra-myocardial electrogram (IMEG) were performed as reference methods. 19 rejection episodes were induced. When acute rejection was seen in histology the animals were treated with pulsed 125 mg methylprednisolone over 5 consecutive days and immunosuppression was raised to sufficient levels. Successful treatment of rejection was controlled by biopsy. All hearts showed a uniform decrease of impedance of about 28.3% +/- 5.5% immediately after implantation, then reaching a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grade 1A to 1B (ISHLT) were accompanied by a statistically significant increase of impedance of 12.2% +/- 2.5%, of grade 2 to 3A of 19.2% +/- 3.2%, and of grade 3B to 4 of 27.0% +/- 2.9%. Sensitivity was 95%, specificity 91%. Successful treatment of rejection led to a uniform decrease of impedance to intramyocardial impedance for high frequencies can reliably indicate alterations of the cell membrane and the intracellular space during acute cardiac allograft rejection. The amount of increase of impedance is a reliable noninvasive parameter to graduate acute cardiac allograft rejection. The success of treatment of rejection can also be monitored by impedance. This noninvasive method is applicable for telemetric rejection monitoring via an implantable device, which would allow continuous rejection surveillance of a patient at home without hospital admission.

In recent years, as the importance of humoral-mediated rejection has increasingly become recognized, the fact that endomyocardial biopsies (BX) evaluated according to the criteria of the International Society for Heart and Lung Transplantation often produce false-negative results has become a matter of concern. To evaluate the reliability of measuring intramyocardial ECG amplitude (IMEG) and immunofluorescence evaluation (FITC-labeled anti-IgG/IgM staining) of endomyocardial biopsies (IFM), heterotopic neck-heart transplantation (HTX) was performed on eight beagles previously sensitized through skin transplantations. After HTX, IMEG, echo, and donor-specific antibodies in serum (IgG, IgM) were determined daily and myocardial biopsies (IFM, BX) were performed once every 2 days. Accelerated (humoral) rejection occurred on the 5th (4th–5th) postoperative day and sensitivity of IMEG, IFM, and BX was 100 %, 75 %, and 12.5 %, respectively. In each case rejection was recognized so early that it was possible to initiate therapy with “restitutio ad integrum”. Our results show that, as opposed to endomyocardial biopsy (IFM, BX), IMEG diagnosis detected humoral-mediated rejection early and with high reliability.

Wir berichten uber eine 28jahrige Patientin, die aufgrund eines Ventrikelseptumdefektes (VSD) mit Eisenmengerreaktion und nachfolgender Herzinsuffizienz NYHA-Stadium IV Herz-Lungen-transplantiert wurde und an den Folgen einer akuten GvHD am 34. postoperativen Tag verstarb.

Verrucous carcinoma of the esophagus is a very rare entity. It has a high mortality. Treatment is different. 14 cases are reported. With this 15th case we report on a 66-year-old female with a verrucous carcinoma of the esophagus and surgical treatment after 4 times of recurrence and unsuccessful endoscopic resection of the tumor. The patient received transthoracic removal of the distal esophagus and interposition of the stomach. The patient recovered completely and was discharged from hospital after 18 days. Considering this case therapeutic options will be discussed.

We report on a patient with an extended corrosive injury of the posterior tracheal wall and left-sided tracheo-esophageal fistula after severe inhalative trauma. Resection of the fistula and necrotic tissue was followed by reconstruction of the posterior tracheal wall with an esophageal patch. Interposition of the stomach was performed to restore upper gastro-intestinal continuity. Revision was necessary due to an anastomotic insufficiency and a recurrent fistula between the trachea and the esophago-gastrostomy on the left side. The stomach was resected and the fistula was covered with a sternocleidomastoideus muscle flap. Several weeks later interposition of the right hemicolon was performed to establish the gastro-intestinal tract and the patient recovered completely, thereafter. q 2003 Elsevier B.V. All rights reserved.

Arterial port-catheter dislocations into the duodenum are rare complications. We report on a 64-year-old male with sigmoid-resection for carcinoma, left hemihepatectomy and arterial port-catheter implantation into the common hepatic artery for liver metastases in both lobes and partial dislocation of the port system into the duodenum. Therefore, the port-catheter system had to be explanted after 8 cycles of cytostatic therapy and the duodenum had to be closed by a suture. Six months after surgery the patient felt well, a new singular metastasis in the right liver lobe could be treated successfully by laserinduced thermotherapy. At present the patient has no evidence for another metastasis.

Mit der bioelektrischen Impedanz konnen Zustandsanderungen stoffwechselaktiven biologischen Gewebes entdeckt werden. Die Methode, ursprunglich entwickelt, um Zelluntergang durch Ischamie zu detektieren, ist an heterotop transplantierten Hundeherzen angewendet worden, um Abstosungsreaktionen des Transplantats zu diagnostizieren.

This is a case report about a 56-year-old female patient with primary pulmonary hypertension who underwent single, right lung transplantation. Five years postoperatively she developed signs of right heart failure. History and physical examination suggested pulmonary artery stenosis. Diagnosis was confirmed by pulmonary angiography. Percutaneous placement of a balloon expandable stent normalized pulmonary artery pressure.

Thoracic duct injuries and chylous fistula are well-known complications of neck dissection, occurring in 1-2% of cases. Management of these injuries can be conservative or operative. Conservative treatment consists of fat restricted diet or total parenteral nutrition reducing the volume of chyle production. Operative management includes exploration of the neck or if necessary open thoracotomy to ligate the thoracic duct. Following cervical thoracic duct ligation only few complications like chylothorax or chylous ascites are described in the literature. To the best authors knowledge, this is the first report in the english literature describing lower-extremity lymphedema following cervical thoracic duct ligation.

SUMMARY. Postoperative chylothorax after injury of the thoracic duct during esophagectomy is a rare but severe complication which may lead to serious problems such as loss of fat and proteins, and immunodeficiency. Without treatment mortality can rise to over 50%. From 1988 to 2005, we treated 10 patients with postoperative chylothorax after 409 resections of the esophagus (2.4%). Of these 10 patients nine underwent transthoracic esophagectomy with gastric pull-up to enable an intrathoracic (n = 7) or cervical (n = 2) anastomosis and one patient received a transhiatal esophagectomy with gastric pull-up and cervical anastomosis. The average amount of postoperative chylus was 2205 mL (200–4500 mL) per day. After a median postoperative interval of 10 days, relaparotomy and transhiatal double ligation of the thoracic duct was performed in nine out of 10 patients. One patient could be managed conservatively. The average amount of chylus was reduced to 151 mL per day (90.5%). Seven patients had no complications, and three suffered from postoperative pneumonia. Two of the patients with pneumonia recovered, and one died. Discharge from hospital, after ligation of the thoracic duct, was possible after a median time of 18 days (11–52). Ligation of the thoracic duct via relaparotomy appeared to be a simple and safe method to treat postoperative chylothorax.

The relevance of sobriety for outcome after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) is still discussed controversially. We conducted a retrospective analysis of 300 patients transplanted for ALD with regard to recurrent alcohol consumption, risk factors for drinking after OLT, and long-term survival. The 300 patients underwent OLT for ALD between 1989 and 2002. Median follow-up was 89 months. Incidence and severity of drinking, survival rates, and causes of death were assessed. Age, gender, duration of pretransplant sobriety, social support, presence of children, and the results of psychosomatic evaluation were analyzed for their impact on recurrent alcohol consumption after OLT. Drinking of various degrees was observed in 19% of ALD patients after OLT. Pretransplant sobriety of less than 6 months, absence of companion in life, presence of young children, and a predicted poor psychosomatic prognosis were associated with an increased risk of recurrent alcohol consumption, whereas age and gender were not independent risk factors. Survival rates of patients who resumed abusive drinking were significantly lower than survival rates of abstinent patients or patients with minor lapses. Recurrent alcoholic liver disease accounted for the vast majority of deaths among patients who resumed abusive drinking after OLT, whereas malignant tumors, infections, and cardiovascular disease were the most common causes of death among abstinent patients. In conclusion, abusive drinking after OLT is associated with poor long-term survival. Analysis of risk factors may help to identify patients with a high risk for recurrent alcohol abuse after OLT.

Purpose: To report the association between hepatocellular carcinoma (HCC) and hepatic focal nodular hyperplasia (FNH) and the possible impact on clinical decision-making with regard to resective approaches in patients with FNH.Material and Methods: We retrospectively analyzed the findings in 77 adult patients who underwent liver resections for FNH between October 1989 and September 2001 at our center. HCC within the confines of FNH was found in two patients. We demonstrate the magnetic resonance imaging (MRI) and macroscopic and microscopic findings.Results: Presurgical MRI demonstrated heterogeneous signal characteristics of moderately hyperintense FNH on T2-weighted images and, after IV administration of super-paramagnetic iron oxide particles, HCC in FNH was barely delineable. Both patients underwent successful right hemihepatectomy to remove the suspicious FNH with diameters of 12 and 14 cm; intralesional HCC diameters were 3 and 5 cm, respectively. Patients could be rapidly dismissed. However, one patient died after recurrence of HCC 1.5 years after surgery, whereas the other patient continues tumor-free 4 years after surgery. Alpha-feto-protein was normal in both patients.Conclusion: In FNH with rapid growth tendency and heterogenic MR appearance, surgical removal should be considered to overcome the risk of inadequate therapy in the very rare group of patients with HCC in association with FNH.

J Thorac Cardiovasc Surg 1997;114:285-7

Mycophenolate mofetil (MMF) is approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation as well as for pediatric patients after kidney transplantation. MMF, a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), blocks de novo purine synthesis which leads to an effective inhibition of proliferation selectively in T and B lymphocytes, smooth muscle cells, and fibroblasts. MMF shows additional effects with inhibition of the expression of activating and adhesion molecules on the surface of lymphocytes. The beneficial safety profile with distinct side effects compared to calcineurin inhibitors (CNI) enable efficacious combination with ciclosporin or tacrolimus as de novo therapy after liver transplantation. Furthermore, recent studies show the possibility to reduce CNI induced toxicities by adding MMF to primary immunosuppression. MMF is also used to enable early steroid withdrawal after liver transplantation. MMF can increase efficacy of immunosuppressive therapy and thereby support the treatment of steroid resistant acute rejections, chronic rejections and chronic graft dysfunction.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited disorder characterized by cutaneous and mucosal telangiectasias, epistaxis and arteriovenous malformations in lung, liver, central nervous system, and gastrointestinal tract. Mutations in the genes for endoglin (ENG) and for activin A receptor type II-like kinase 1 (ALK-1) have been identified to be associated with HHT. Intrahepatic manifestation in HHT might lead to the requirement of liver transplantation. We report here on 6 liver transplanted patients and 2 who were scheduled for liver transplantation due to intrahepatic HHT, in whom both genes were sequenced. Mutation analysis revealed in all patients the presence of mutations in ALK-1. In conclusion, these results are of possible prognostic value concerning the need of liver transplantation in HHT patients.

Verrucous carcinoma of the esophagus is a very rare entity. It has a high mortality. Treatment is different. 14 cases are reported. With this 15th case we report on a 66-year-old female with a verrucous carcinoma of the esophagus and surgical treatment after 4 times of recurrence and unsuccessful endoscopic resection of the tumor. The patient received transthoracic removal of the distal esophagus and interposition of the stomach. The patient recovered completely and was discharged from hospital after 18 days. Considering this case therapeutic options will be discussed.

A 36-year-old female presented with unspecific epigastric discomfort, without weight loss, night sweat or fever. Ultrasound and computed tomography showed a solid tumor with a diameter of 9 cm in the left upper abdomen, without any connection to the stomach, the pancreas or spleen. Laparoscopy showed a connection to parts of the greater omentum. Two days after laparoscopic resection the patient was discharged from hospital. Histology revealed the rare diagnosis of a dermoid cyst. A possible malignant degeneration of the tumor has to be considered, and therefore the tumor should be resected. Since the operation the patient is asymptomatic and without tumor recurrence.

Background. Mycophenolatemofetil (MMF) combined with calcineurin inhibitors (CNIs) as immunosuppression after orthotopic liver transplantation (OLT) is still under discussion. We retrospectively investigated the immunosuppressive potency of MMF for treatment of steroid-resistant acute rejection (AR) or chronic rejection (CR), chronic graft dysfunction, and CNI-induced toxicity in patients after OLT. Methods. Between 1988 and 2001 we performed 1,386 OLTs in 1,258 patients. Since 1995, 191 patients have received MMF after OLT for steroid-resistant AR or CR, chronic graft dysfunction (115 patients), and CNI-induced toxicity (76 patients). The mean follow-up time was 56 months. Results. Of 47 patients with steroid-resistant AR, 12 had been treated with OKT3, without resolving the rejection. Overall, bilirubin and transaminases decreased significantly within 2 weeks after the addition of MMF, and liver function normalized in 38 patients. Five of eight patients with CR demonstrated stable liver function after a follow-up of 55±8 months; 52 of 60 patients with chronic graft dysfunction improved within 3 months; and 46 of 59 patients with CNI-induced nephrotoxicity improved after MMF treatment and a reduction of CNIs (with a significant decrease in serum creatinine within 2 weeks and an increase of creatinine clearance within 3 months). Clinical symptoms improved in 10 of 12 patients with neurotoxicity and four of five patients with hepatotoxicity. Side effects of MMF, such as gastrointestinal disorders or bone marrow toxicity, occurred in 60 patients (31.4%). The incidence of infections did not increase. Patient survival was 93%, and graft survival was 88.2%. Conclusions. MMF is a potent and safe immunosuppressive agent in OLT recipients for rescue therapy in AR, CR, or chronic graft dysfunction and helps to reduce the serious toxic side effects of CNIs.

Die orthotope Lebertransplantation (OLT) hat die Behandlung der Patienten mit fortgeschrittener terminaler Leberinsuffizienz revolutioniert und ist inzwischen als effektivste Therapie fur diese Patienten etabliert. Vor Einfuhrung der Transplantation hatten diese Patienten keine Langzeituberlebenschancen. Bis zum Jahre 2000 wurden an uber 300 Transplantationszentren weltweit mittlerweile mehr als 80.000 Lebertransplantationen durchgefuhrt. Die derzeitige Frequenz in Deutschland liegt bei ca. 700 Transplantationen/Jahr. Einjahresuberlebensraten von uber 90% und Funfbzw. Zehnjahresuberlebensraten von uber 80 bzw. 75% konnten in den letzten Jahren an verschiedenen Transplantationszentren erreicht werden (Abb. 38.1). Zu diesen Erfolgen hat die Verbesserung der immunsuppressiven Therapie durch Einfuhrung von Cyclosporin A, Tacrolimus und monoklonalen Antikorpern, der Organkonservierung, der chirurgischen Technik sowie des perioperativen intensivmedizinischen Managements wesentlich beigetragen. Abbildung 38.2 zeigt weitere Faktoren mit Einfluss auf die Uberlebensrate nach OLT.

Initial graft function following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Despite several efforts to provide scoring-systems for initial graft function, there is still a lack of a generally accepted classification scheme. The previously published systems assessed initial graft function based on the first postoperative days or weeks using liver-related laboratory parameters. It was shown that in most cases the scoring-systems did not correlate with patient survival. We intended to refine the definition of initial graft function in order to provide a survival based classification system. In a retrospective analysis of 761 patients following primary liver transplantation, a new scoring-system for early postoperative graft function was developed. Statistically significant differences in long term survival were calculated for ALAT, ASAT, bile production and prothrombin activity on days 1, 3, 7, 14. Points were then assigned according to the degree of survival: improved survival=1 point, poor survival=2 points. Patients were split into three groups corresponding to initially good, moderate and poor function. Applying this score, early and late patient survival rates and incidence of initial non-function were statistically significantly different. This was in contrast to the Gonzalez and the Ploeg-Maring classification scales, which are based on arbitrarily chosen cutoff levels. Retransplantation rates and postoperative morbidity were comparable both for the new and the older systems. We can conclude that the presented refined scoring-system for initial graft function provides a significant correlation to patient survival and initial non-function. We recommend the refined system for future studies.

Mesenteric artery occlusions are rare complications of Thrombangiitis obliterans (Buerger's disease). We report on a 30-year old male with Thrombangiitis obliterans and mesenteric occlusion as a complication of this disease. Because of unclear abdominal pain, laparoscopy was performed which showed small bowel infarction and reduced liver perfusion. After small bowel resection and a second examination, ischemia of the intestinum continued. Angiography was performed, which showed central occlusion of the celiac trunk and the superior mesenteric artery. Relaparotomy with the embolectomy of the superior mesenteric artery, venous bypass from the sup.mes.art. to the hepatic arteries and repeated small bowel resection was performed. The patient recovered completely and was discharged from hospital after 3 weeks. After a further admission to the hospital 3 weeks later with abdominal pain caused by acute occlusion of the right colonic artery and severe ischemia of the right hemicolon, a right hemicolectomy was performed. Now, one year after the last hospital admission, the patient shows no sign of having any abdominal problems.

Arterial port-catheter dislocations into the duodenum are rare complications. We report on a 64-year-old male with sigmoid-resection for carcinoma, left hemihepatectomy and arterial port-catheter implantation into the common hepatic artery for liver metastases in both lobes and partial dislocation of the port system into the duodenum. Therefore, the port-catheter system had to be explanted after 8 cycles of cytostatic therapy and the duodenum had to be closed by a suture. Six months after surgery the patient felt well, a new singular metastasis in the right liver lobe could be treated successfully by laserinduced thermotherapy. At present the patient has no evidence for another metastasis.

Background. Intrahepatic Osler's disease with multiple arteriovenous malformations and high intrahepatic shunting may lead to secondary pulmonary hypertension followed by right-heart stress and insufficiency. Until now, therapy with arterial embolization, banding, or ligation of the hepatic arteries is still limited and provides unsatisfactory long-term results. Liver transplantation offers another therapeutic option. Methods. We report on four patients with intrahepatic involvement of Osler's disease who were liver transplanted between 1995 and 1999. All patients suffered from restricted liver function and right-heart insufficiency with multiple cardiac decompensations. One patient received one course of embolization, and another received six courses of embolization and then banding of the main hepatic artery before transplantation. In both patients, the clinical symptoms improved for only a few months. Results. All patients had high degrees of intrahepatic arteriovenous shunting, and cardiac output measurements were between 8.0 to 13.3 L/min preoperatively. Preoperative mean pulmonary artery pressure was between 24 to 35 mmHg. After liver transplantation, cardiac output and right-heart diameter decreased or normalized and pulmonary pressure reached the normal range after 2 months. All patients received tacrolimus and steroids for primary immunosuppression. In one case, temporary hemodialysis was necessary for 2 weeks after transplantation, but renal function recovered completely. After follow-up time of 12 to 65 months, all patients had normal graft function and good cardiopulmonary condition. Conclusions. Indication for liver transplantation should be considered in patients with intrahepatic Osler's disease, high arteriovenous shunting with right-heart stress, and restricted liver function before irreversible fixed pulmonary hypertension leads to severe right-heart insufficiency or failure. Our therapeutic regimen of early liver transplantation in the case of intrahepatic Osler's disease in four patients has promising results.