W. Lauchart

Adenine nucleotide metabolism and its relation to organ viability in human liver transplantation

The relationship between adenine nucleotide metabolism and ischemic damage was studied in human liver. Thirty transplanted grafts were divided into two groups assording to their functional outcome. Cellular adenine nucleotide levels were assayed by high-performance liquid chromatography. During cold ischema, the adenosine triphosphate (ATP) level was not correlated with graft function, but two grafts with low total adenine nucleotides (TAN) levels showed poor function after transplantation. After recirculation, the ATP level showed good recovery in grafts that functioned satisfactorily (n=24), 5.47±1.51 mUmol/g dry weight), but remained low in poorly functioning grafts (n=6), 3.30pL 1.68 mUmol/g dry weight) (P<0.01). Bile production, used as a parameter of initial function, was observed shortly after implantation in 17 of 24 grafts that functioned satisfactorily, but in only 1 of 6 poorly functioning grafts. It is concluded that loss of ademine nucleotides and lack of bile production during transplantation are good markers of damaged grafts in human liver transplantation.

HBV-vaccination in recipients of kidney allografts

Recipients of renal transplants were vaccinated with 20 ng hepatitis B surface antigen aluminium-adsorbed vaccine in order to gauge their resistance to hepatitis B infection, to which these patients are at high risk. The patients were given three 40 micrograms doses of the vaccine over a period of six months and their antibody titres were measured. Only 9% of patients developed antibodies to hepatitis B and it was established that if possible all patients should receive at least one injection of hepatitis B vaccine prior to surgery.

Approach to Primary Liver Cancer

Primary malignant liver tumor is the most frequent malignoma worldwide. This is due mainly to a high incidence in Asian and African countries. Particularly in these countries, but also in Europe and other continents, most hepatocellular carcinomas are associated with liver cirrhosis. In contrast to this high frequency, therapeutic experience with hepatocellular or cholangiocellular carcinomas has been very limited, at least in Europe. This is not only because of the relative infrequen-cy of this tumor in our countries in comparison with other malignancies ; such tumors were generally diagnosed very late and liver resection therapy was uncommon, particularly in cirrhotic but also in non-cirrhotic patients. Similarly, experience with non-surgical methods is limited. This situation has changed in part within the past few years : ultrasonography and CT scanning, as well as the determination of alpha-fetoprotein, have significantly increased the number of diagnosed tumors and have enabled diagnosis in earlier stages. More specific methods of liver surgery have been developed and, finally, liver grafting was added. Many other approaches for therapy were also instituted. Thus, therapeutic access to a primary liver malignoma became more frequent.

Diagnosis and Management of Metastatic Gastrinoma by Multimodality Treatment Including Liver Transplantation:Report of a Case

Neuroendocrine tumors of the pancreas are being recognized with increasing frequency, not because the incidence has increased, but as a result of improvements in diagnostic tools such as radioimmunoassays for a variety of circulating peptides, and imaging methods that include positron emission tomography (PET) and immunoscintigraphy. Nevertheless, establishing the diagnosis of a neuroendocrine tumor is always a challenge to the clinician from both diagnostic and therapeutic perspectives. Liver transplantation as the ultimate therapeutic, or at least palliative, option for hepatic metastases has produced contradictory results over the past decade. We report herein the case of a 23-year-old woman who, after being diagnosed with gastrinoma in 1989, underwent the complete therapeutic array including liver transplantation for hepatic metastases in 1991. Although an extrahepatic tumor recurred 2 years later, for which double chemotherapy with 5-FU and streptozotocin was given, she is currently leading a normal life with a full-time job. This case prompted a critical review of the current literature on diagnosis and medical and surgical treatment.

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN 18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28–50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112–160. In the animals treated with FN 18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN 18 but was successful in two animals with a low antimouse response. These four animals survived 1 GO-SOS days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Developments in liver transplantation

Liver transplantation has gained increasing interest. While liver grafting for tumor is successful over prolonged periods only in its early course, liver grafting for end-stage cirrhosis may lead to a long survival. Liver grafting in children is the most successful indication; in adults the results depend largely on timing and indication. Actual developments are mainly seen in the following points: a. Improvement in immunosuppression by use of Cyclosporin A. The resorption and metabolism of the drug, in relation to liver function, have to be carefully observed. b. The tendency to perform liver grafting electively instead of in emergency. c. Improvement in operative management, particularly the use of veno-venous bypass. d. The best possible anaesthesiological and intensive care management for the patients. It can be expected, that these developments will enable continuous improvement of results, particularly in an elective situation. One hundred and forty liver grafts have been done in our institution and the results are discussed herein. Progress in liver transplantation is marked by steadily growing numbers of liver grafts performed, and of centers performing grafts, as well as by improved success rates and the recommendation of the U.S. National Institutes of Health, based on discussions at a liver transplantation consent meeting, held in June 1983. This interest is also reflected in discussions among the medical and non-medical community. The first section of this paper will deal with the present state and results of liver grafting particularly, at our own institution and some actual developments in this field will be discussed.

Diagnostische Relevanz der veränderten Expression von MHC-Antigenen im menschlichen Lebertransplantat

Die Diagnostik der Abstosung nach Lebertransplantation basiert zu einem wesentlichen Teil auf der histopathologischen Beurteilung von Leberbiopsien. Die histologischen Veranderungen bei Transplantatabstosung sind das Resultat der immunologischen Prozesse, die durch den Unterschied in den Gewebeantigenen (MHC oder HLA-Systeme) zwischen Donor und Empfanger ausgelost werden. Wie in den letzten Jahren zunehmend klar geworden ist, wird die Expression der MHC Antigene im Gewebe durch immunologische Prozesse verandert (1). Die Anderung der Expression sowohl von Klasse I Antigenen (HLA-A,B,C) als auch Klasse II Antigenen (HLA-DR,DP,DQ) kann mit monoklonalen Antikorpern immunhistologisch nachgewiesen werden (2 — 4). Wie wir bereits fruher zeigen konnten, kann es nach Lebertransplantation zu einer wesentlichen Veranderung der MHC-Expression kommen (5). In dieser Arbeit werden Verlaufsanalysen der MHC-Expression nach Lebertransplantation beschrieben und ihre diagnostische Bedeutung diskutiert.

189. Operatives Vorgehen beim Caroli-Syndrom

SummaryOver 2 years, nine patients with Carolis disease were treated. The surgical procedure depended on the kind of intrahepatic manifestation: four partial liver resections; one liver transplantation; two bile-duct resections; two internal drainage procedures; later, one lithotripsy. Because of the risk of malignancies resection was the preferred procedure. In total intrahepatic lithiasis, extracorporal lithotripsy is an alternative.ZusammenfassungIn 2 Jahren wurden 9 Patienten mit Caroli-Syndrom behandelt. Je nach intrahepatischer Ausdehnung wurden verschiedene operative und nicht-operative Verfahren angewandt: 4 Leberteilresektionen, 1 Lebertransplantation, 2 Gallenwegsresektionen, 2 innere Drainagen, später 1 Lithotripsie. Zur Erreichung von Symptomfreiheit werden unter Berücksichtigung des Malignitätsrisikos resezierende Verfahren angestrebt. Bei Befall der gesamten Leber kann die Lithotripsie eine Alternative sein.

261. Ergebnisse der erweiterten Leberresektion bei sekundären Lebermalignomen

SummaryBetween 1976 and 1987, 124 hepatic resections for colorectal metastases (59 hemihepatectomies, 12 extended liver resections, 16 resections of 1 or more segments and 19 atypical, e.g., wedge resections) have been performed at the Hannover Medical School. Overall hospital lethality was 7%. Survival rates were 81%, 69%, and 25% after 1, 2, and 5 years, respectively. Significant prolonged survival times have been observed in patients with metachronous metastases (median survival time 57.4 vs. 19.3 months). Hospital lethality after extended resections was 17%, the survival rates being 66%, 49%, and 40% after 1, 2, and 3 years, respectively.ZusammenfassungDie Operations-Letalität der von 1976–1987 an der MHH durchgeführten 124 Leberresektionen bei colorectalen Metastasen (Hemihepatektomie rechts [n = 40] bzw. links [n = 19], erweiterte Leberteilresektion [n = 12], Resektion eines oder mehrerer Segmente [n = 16], atypische Resektionen, z. B. Keilexcisionen [n = 19]) betrug 7%. Die Überlebenswahrscheinlichkeit wurde nach 1 Jahr mit 81%, nach 2 J. mit 69% und nach 5 J. mit 25% errechnet. Signifikant längere Überlebenszei ten hatten Patienten mit metachroner Metastasierung (mediane ÜLZ 57,4 vs. 19,3 Monate bei synchronen Metastasen). Die Operations-Letalität bei erweiterten Resektionen (Trisegmentektomie rechts bzw. links) betrug 17%, die ÜLZ nach 1 J. 66%, nach 2 J. 49% und nach 3 J. 40%.

269. Resektion Von Huuscarcinomen - Operabmtat, Technik und Ergebnisse

SummaryPalliative treatment of hilar carcinoma has been improved by transhepatic and endoscopic techniques. Moreover, advances in liver surgery have allowed the resection of a higher percentage of these tumors, which sometimes do not infiltrate deeply into the hepatic parenchyma. Resection may thus be worthwhile. Of 65 central hilar tumors, 31 have been resected, in 17 of which resection was combined with partial hepatectomy. The 1 year survival of patients after resection is about 65%. Resection of these tumors requires skilful and mostly time consuming preparative surgical technique.ZusammenfassungNeben verbesserten Möglichkeiten der Drainagebehandlung von Hiluscarcinomen haben Fortschritte der Leberchirurgie auch zu einer höheren Rate der Resektabilität dieser Tumoren geführt. Möglicherweise ist die Infiltrationstiefe mancher dieser Tumoren begrenzter als bei anderen Malignomen, so daß Resektion geeignet ist. Bei 65 zentralen Hilustumoren konnte 31mal ein resezierendes Verfahren, davon 17mal mit Teilleberresektion angewandt werden. Die 1-Jahres-Überlebenshöhe nach Resektion liegt bei 65%. Die Operation erfordert ein sehr sorgfältiges, häufig zeitaufwendiges präparatives Vorgehen.