[What is the risk of resection of the right hepatic artery in resection of central bile duct carcinoma?]. / Wie risikoreich ist die Resektion der rechter Leberarterie bei der Resektion eines zentralen Gallengangskarzinom?

Between 1990 and 1994 we performed tumor resection on 21 patients with a cholangiocarcinoma of the porta hepatic. In 5 cases a segmental resection/ligature of the patent right hepatic artery was performed. The postoperative course of recovery in these 5 patients was compared to that of the other 16 patients. We found no significant differences in either the postoperative course of recovery or the laboratory parameters of the two groups. There was no clinical liver necrosis or bile duct necrosis (which would have manifested itself as a leak in the anastomosis) in either group. On the basis of our experience, segmental resection/ligature of the right hepatic artery as part of a radical cholangiocarcinoma resection is possible provided that the right portal vein is patent.

Sequential transarterial chemoembolization for unresectable advanced hepatocellular carcinoma.

PURPOSE: The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of sequential transarterial chemoembolization (TACE) for patients with unresectable advanced hepatocellular carcinoma (HCC). METHODS: Twenty-one consecutive patients with unresectable T3 and T4 HCC were treated by sequential TACE (median time interval between treatments 7 weeks) up to six times with an emulsion of lipiodol, epirubicin, and cisplatin. All TACE procedures were performed as unilobar or whole-liver chemoembolization. RESULTS: An average of 3.9 TACE procedures were performed per patient. One primary and two secondary technical failures occurred. No procedural death was observed. After exclusion of the patient with the primary technical failure and 3 patients with extrahepatic disease, the survival rates for the remaining 17 patients at 6, 12, 18, and 24 months were 70.6%, 52.9%, 44.1%, and 33.1%, respectively. CONCLUSION: Sequential TACE is a safe procedure in patients with unresectable advanced HCC and feasible in most cases. It seems to prolong the survival time compared with historical series of untreated patients.

[Early clinical experiences with MR-guided laser-induced thermotherapy (LITT) of liver metastases in preoperative care]. / Erste klinische Erfahrungen zur MR-gesteuerten laserinduzierten Thermotherapie (LITT) von Lebermetastasen im präoperativen Einsatz.

PURPOSE: To evaluate the LITT-induced changes with the aid of MRT and correlate these with histopathological findings. MATERIAL AND METHODS: Five patients with solitary colorectal liver metastases were treated by means of MR-guided LITT before liver resection. Application time and energy of the Nd:YAG laser (1064 nm) was 10-20 minutes and 4.5-8.8 W. MRT monitoring during the LITT was carried out with temperature-sensitive T1 weighted sequences (FLASH-2-D, turbo FLASH). The extent of the induced necrosis as seen on MR was compared with the unfixed specimen and with the histopathological findings. RESULTS: The extent of necrosis visible by MRT correlated with the histopathological findings with an accuracy of 95.3% +/- 4.2%. Following single treatments (three cases) the metastases suffered a reduction of 24%-55% of their original volume. In two patients a second application produced laser-induced necrosis of 78% and 98% of volume. In these two patients a temperature sound was used for measuring regional heating and showed an exact correlation with MR thermometry. CONCLUSION: The results of pre-operative MR-guided LITT indicates the potential of this form of treatment for obtaining reproducible tumor necrosis of liver metastases.

Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine-based regimen: a controlled, prospective, randomized trial.

As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone, azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3-d course of high-dose methyl-prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CsA administration, conversion to FK506 as another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the two groups. In the CsA-based group, three additional rejection episodes were classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity versus rejection--or why conversions between cyclosporine A and FK506 were performed after liver transplantation.

The introduction of cyclosporine A (CsA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients in still compromised by rejection, over-immunosuppression-induced infection and immunosuppression-associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 60 treated with FK506 and 61 patients treated with CsA-based immunosuppression. Five patients treated primarily with CsA (8.3%) were converted to FK506 therapy because of refractory acute of chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re-LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the early postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p = n.s.). Five patients treated primarily with FK506 were converted to CsA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506- and 36.7% of CsA-treated patients. 8.3% of FK506-treated patients and 11.7% of CsA-treated patients required hemodialysis (p = n.s.) There patients were converted from FK506 to CsA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CsA, and all conversions from FK506 to CsA (13.3%) were performed because of neuro- or nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

The optimal immunosuppressant after liver transplantation according to diagnosis: cyclosporine A or FK506?

Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppressive regimen, the incidence of early postoperative neurotoxicity was significantly lower in patients transplanted owing to HBV disease, alcoholic cirrhosis and various other liver diseases summarized than in patients transplanted due to HCV disease receiving FK506 therapy. During the 1st year, the incidence and severity of rejection in patients transplanted due to alcoholic cirrhosis and PBC was significantly lower in patients treated with FK506 (11.1% for both groups) compared with those patients receiving CsA (54.5% and 60.0%, respectively; p < or = 0.05. Furthermore, this was accompanied by a lower incidence of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of polymerase chain reaction from plasma and buffy coat with antigen detection and occurrence of immunoglobulin M for the demonstration of cytomegalovirus infection after liver transplantation.

We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag assay, and the determination of IgM antibodies by ELISA for the diagnosis and follow-up of cytomegalovirus infection. Thirty patients were followed after liver transplantation (LTX). We compared the tests to assess their clinical usefulness. Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and Ag test. Sixteen patients were negative in both procedures. There was a 97.2% concordance between PCRs done from plasma or buffy coat. The concordance of results of PCR and Ag test in single samples was 94.3%. Discordant results were found in 5.6% of samples. Discordance was observed in the early and the late phase of CMV infection and was due to positive PCRs preceding positive Ag tests for 1-3 weeks in one-half of the patients. IgM antibodies were first observed after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and Ag tests preceded clinical manifestation of CMV disease by a 1 week median (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of 2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and specificity of both PCR and Ag test were identical, 100% and 76%, respectively. However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was 84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable procedures for early detection and monitoring of CMV infection. PCR can become positive earlier than the Ag test, but it is technically more demanding to perform. The demonstration of IgM antibodies is of little practical help because an antibody response occurs too late in relation to infection.

Comparison of FK506- and cyclosporine-based immunosuppression in primary orthotopic liver transplantation. A single center experience.

FK506 has been proven effective for prevention and treatment of liver allograft rejection. Herein, we compare FK506-based immunosuppression with an effective quadruple immunosuppressive regimen, including cyclosporine and antithymocyte globulin. The results of a single center participating in the European multicenter FK506 study are reported, including immunosuppressive efficacy as well as toxicity. One-year patient and graft survival was 96.7% and 90.0% for the CsA group and 90.2% and 88.5% for the FK506 group, which is not statistically different. The incidence and severity of acute rejection episodes during the first postoperative year was similar in both treatment groups with 34.4% and 33.3% for the FK506 and CsA treatment group, respectively. Immunosuppressive potency was better for the FK506 group compared with the CsA group according to the incidence of chronic rejection. Furthermore, 5 patients (8.3%) required conversion to FK506 for immunological reasons, i.e., refractory acute or chronic rejection. The incidence of moderate and severe neurotoxicity during the early postoperative period was higher in the FK506 group (21.3%) compared with the CsA group (11.7%), while the incidence of renal insufficiency and acute renal failure was similar (18.0% and 18.3% for the FK506 and CsA treatment groups, respectively). The incidence of CMV infection was significantly higher under treatment with CsA (25.0%) than with FK506 (6.6%) (P < or = 0.05), while the incidence of pneumonia (13.1% and 13.3%), cholangitis (29.5% and 26.7%), and urinary tract infection (39.3% and 28.3% for the FK506 and CsA treatment groups, respectively) was similar in both treatment groups. However, infection was more serious in some cases treated with FK506, and evolved as the main cause of death in the FK506 treatment group. Therefore, caution should be paid to over immunosuppression and toxicity in FK506-treated patients. Regarding the monitoring of FK506, FK506 plasma level failed to be a reliable indicator, and therefore we recommend measurement of whole blood FK506 levels. Our data indicate that immunosuppressive potency of FK506 is greater than that of CsA, especially concerning the incidence of chronic rejection.

[Cause of death after liver transplantation: an analysis of 41 cases in 382 patients]. / Todesursachen nach Lebertransplantation: eine Analyse von 41 Fällen bei 382 Patienten.

UNLABELLED: The aim of this study was to analyse the causes of death after liver transplantation in order to find and to avoid preventable fatal complications if possible. METHODS: Between September 1988 and September 1993 415 orthotopic liver transplantations in 382 patients were performed at the Rudolf Virchow University Hospital in Berlin. During the same interval 41 (10.7%) of these patients died. Their clinical records were reviewed. RESULTS: The main cause of death was infection (29.3%), followed by recurrent malignancy (21.9%). Less patients died because of hepatitis B-reinfection (14.6%), chronic rejection (7.3%), hemorrhage (7.3%), cardiac failure (7.3%), trauma (4.8%), hypoxia (4.8%) and recurrence of alcoholic liver disease (4.8%). There was a wide spectrum of opportunistic infectious agents with CMV and Pneumocystis carinii being the most important pathogenic organisms. Only one isolated bacterial infection as principle cause of death was found. In all fatal infections the lung was the primary site of infection, 7 patients additionally developed sepsis. Altogether 75 patients (19.6%) with hepatitis B-cirrhosis were transplanted. Six of them (8%) developed a fatal hepatitis B-reinfection. Malignancy was the indication for OLT in 41 patients (10.7%). Six of these patients (14.6%) died because of recurrent tumor. Regarding the whole series, most deaths occurred four to twelve months (58.5%) and only five (12.2%) during the first month after OLT. CONCLUSION: Recurrence of primary disease is an important factor regarding total mortality. Therefore it is necessary to practise a careful selection of liver transplant recipients. In the future more attention needs to be drawn towards prevention, identification and management of opportunistic infections.

[Is liver abscess still an indication for liver resection?]. / Gibt es noch eine Indikation zur Leberresektion bei Leberabszessen?

AIM: The standard therapy for liver abscesses consists of percutaneous drainage. In certain cases a liver resection may be indicated. The indication for liver resection in six patients with liver abscess is analysed retrospectively. METHODS: Between 7.7.87-13.10.93 six patients (4 male, 2 fem.) in the age of 40-72 years (mean 59 yrs.) underwent liver resection for liver abscess at our institution. The patients suffered from symptoms of a progressive liver abscess formation: fever, hepatomegaly, loss of weight, jaundice and anorexia. Abscess localization was performed preoperatively by ultrasound and CT. Drainage attempts were unsuccessful in these patients, resections were carried out for suspicion of malignancy or during a laparotomy due to other reasons. RESULTS: Liver resections were left and right hemihepatectomy (1x each), left lateral resection (3x) and one wedge resection. Intraoperative blood transfusion requirements were not different from those of other indications for resection. Postoperative hospitalization lasted 12-33 days (mean 19 days). The postoperative course was uneventful, in one case a hematoma at the resection site required drainage. CONCLUSION: Resection for liver abscesses is indicated only in exceptional cases but allows for definite therapy.

[Graft-vs.-host reaction: a severe complication after orthotopic liver transplantation]. / Graft-vs.-host-Reaktion: eine schwere Komplikation nach orthotoper Lebertransplantation.

INTRODUCTION: Patients with solid-organ transplantation are at risk for Graft-versus-host disease (GVHD) even though GVHD is a rare phenomenon after orthotopic liver transplantation (OLT). CASE REPORT: The 30 yrs old male patient received an ABO compatible orthotopic liver graft for acute liver failure due to intoxication with amanita phalloides. Twenty-four days after OLT the patient developed high temperatures up to 40.0 degrees C and pancytopenia and was treated for CMV-infection. On postoperative day (POD) 32 an erythematous maculo-papular rash developed. A drug induced toxic epidermal necrolysis was suspected and treated with plasmapheresis for three days. Acute renal failure and respiratory insufficiency occurred while liver function was not impaired. A skin biopsy at that time showed no specific signs for GVHD. On POD 42 HLA-typing of circulating lymphocytes presented donor HLA phenotype and GVHD was established. Therapy with ATG was started but the clinical status of the patient did not improve. Following administration of OKT3 on POD 48 a reduction of activated CD-3 lymphocytes from 90% to 60% could be achieved. Due to the low platelet count the patient died of intracerebral hemorrhage on POD 52. CONCLUSION: Since a fully developed GVHD is rare after OLT and the similarity of the clinical findings to viral or drug induced diseases is high, diagnosis is often made late in the course of the disease. Furthermore, therapeutic measures for GVHD are scarce and diagnosis has to be established as early as possible, hence pretransplant procurement of donor and recipient mononuclear cells for later study should be considered to decrease the time period between clinical suspicion and diagnosis.