K. Oldhafer

Ex-vivo resection techniques in tissue-preserving surgery for liver malignancies

Abstract Some primary and secondary liver tumours are not absolutely irresectable, but cannot be resected using a conventional approach because of the limited warm ischaemia tolerance of the liver or poor accessibility of the tumour region. In such situations, the techniques of ex vivo liver surgery, pioneered by Rudolf Pichlmayr some 10 years ago, offer new chances for R0 resection. All the three different approaches, namely ”in situ”-, ”ante situm”-, and ”ex situ” resection, require the use of measures originally developed for transplantation, such as hypothermic liver perfusion and veno-venous bypass. They differ mainly in the extent to which major vessels are divided in order to achieve optimal mobility of the organ. The results show that radical resection can be achieved accomplished in many cases. If necessary, complex vascular reconstructions can be performed. Although perioperative morbidity and mortality are high, there are a number of long-term survivors. Tumour recurrence, however, remains the main problem over the long term. In conclusion, ex vivo liver surgery is an important extension of surgical treatment possibilities. However, the procedure is suitable only for a small number of carefully selected patients and should be reserved for use in specialised centres. Furthermore, in view of the fact that the results are not yet optimal, additive and adjuvant treatment modalities are needed.

Total hepatectomy and liver transplantation for metastatic neuroendocrine tumors of the pancreas - a single center experience with ten patients.

Abstract  Background: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. Methods: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. Results: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. Conclusions: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure.

Reactivated fulminant hepatitis B virus replication after bone marrow transplantation: clinical course and possible treatment with ganciclovir

A female chronic hepatitis B virus carrier (HBV-DNA negative) suffered from simultaneous hepatitis B virus and cytomegalovirus reactivation after in vivo T cell depletion preceding transplantation of an in vitro T cell depleted marrow graft for treatment of acute leukaemia. Interstitial pneumonia developing after bone marrow transplantation was successfully treated with ganciclovir (day 13 until day 46). The initially unnoticed extensive hepatitis B virus replication finally led to clinical hepatitis (day 85) and liver failure (day 96). Liver transplantation was performed, but the patient died from septicaemia. Retrospective analysis of hepatitis B virus DNA revealed that the HBV replication started immediately after T cell depletion and was completely suppressed during ganciclovir administration. Screening for HBV-DNA seems to be mandatory in comparable cases, and antiviral chemotherapy should be seriously considered.

Subacute liver failure induced by phenprocoumon treatment.

We report on a 39-year-old woman suffering from deep venous thrombosis due to a heterozygous factor-V-Leiden mutation with resistance to activated protein C. Four months after beginning oral anticoagulation, generalized jaundice appeared. Subsequently, subacute liver failure developed necessitating an orthotopic liver transplantation. Histopathology showed features of extensive liver cell necrosis without evidence of a substantial inflammatory infiltrate. Based on histopathology and exclusion of other liver diseases, phenprocoumon-induced liver failure was diagnosed. Five months after transplantation the patient is well with normal liver function tests. Because of the widespread use of oral anticoagulants, not only bleeding complications but also hepatotoxicity should be considered in therapy supervision.

In-situ, ante-situm, and ex-situ surgical approaches for otherwise irresectable hepatic tumors

SummaryBackground: Primary liver tumors or liver metastases may be either irresectable, or only resectable at high risk because of their local relation to important vascular structures (hilum of liver, venous confluens, V. cava).Methods: Technically advanced methods of liver resection based on hypothermic perfusion are described, analyzed, and discussed.Results: The techniques of ex-situ, ante-situm, or in-situ liver surgery under hypothermic perfusion permit resection under complete vascular occlusion without considerable time limitations, and with optimized exposition. If required, extended vascular reconstructions may be performed. The results, however, show that these techniques of resection are associated with a relevant morbidity and mortality, although radical resection can be achieved in many instances. Good results can be obtained with increasing experience and optimized indications in selected cases.Conclusions: These advanced approaches to liver resection have enriched the surgical armament and can be useful in defined situations.ZusammenfassungGrundlagen: Primäre Lebertumoren oder Lebermetastasen können aufgrund ihrer Lagebeziehung zu kritischen Gefäßstrukturen (Leberhilus, venöser Konfluens oder V. cava) nicht oder nur mit hohem operativem Risiko resezierbar sein.Methodik: Technisch fortgeschrittene Methoden der Leberresektion unter hypothermer Perfusion werden vorgestellt, analysiert und diskutiert.Ergebnisse: Die Techniken der Leberresektion unter hypothermer Perfusion ex situ, ante situm oder in situ erlauben eine Resektion unter komplett ischämischen Bedingungen, ohne relevante Zeitlimitierung und mit optimaler Exposition. Falls erforderlich, können auch komplexe Gefäßrekonstruktionen durchgeführt werden. Die Ergebnisse zeigen, daß diese Verfahren der Resektion mit einer relevanten Morbidität und Mortalität verbunden sind, in vielen Fällen jedoch eine radikale Resektion erreicht werden kann. Mit zunehmender Erfahrung und optimierter Indikationsstellung können in ausgewählten Fällen gute Ergebnisse erzielt werden.Schlußfolgerungen: Insgesamt erweitern diese fortgeschrittenen Verfahren der Leberresektion das Rüstzeug des Chirurgen und können bei bestimmten Indikationen sinnvoll sein.

Kidney Retransplantation in Sensitized Patients: Experience with a New Immunosuppressive Protocol

The results of retransplantation in those patients with high panel reactive antibodies (PRA) are worse than in other recipients. Nevertheless the number of retransplantations and the number of sensitized patients on the waiting list are increasing. To improve the results we used a new immunosuppressive strategy with a single shot of intraoperative ATG followed by a high dose mycophenolate mofetil maintenance immunosuppression. The working mechanism of mycophenolate mofetil with lymphocyte suppression is likely to improve the results in those patients, especially in conjunction with an intraoperative ATG bolus.

Experience with Fourth Time Kidney Transplantation

Between December 68 and February 97, 2991 kidney transplantations were performed in our unit: 2514 were first transplants, 297 were second transplants, 63 third transplants, 15 fourth transplants and 2 fifth transplants. We report our experience with 10 fourth transplants in adult recipients performed in our unit between October 80 and October 96.

Bedeutung der Spenderorganqualität bei der Lebertransplantation — Entscheidungsfindung durch subjektive und objektive Kriterien bei 229 Organentnahmen

Empfangeruberleben und Transplantatfunktion hangen entscheidend von der Spenderleberqualitat ab. Die letzte Beurteilung der Spenderleberqualitat hangt trotz Weiterentwicklung objektiver Methoden von der subjektiven Entscheidung des Chirurgen ab. Diese Entscheidungsfindung wurde bei 229 Organentnahmen prospektiv und im Detail dokumentiert. Sie gestattet eine hoch signifikante Vorhersage des Patientenuberlebens und ist hier besser als der MegX-Test. Entscheidende Einzelkriterien sind Konsistenz und Fettgehalt der Leber. Fleckigkeit, Randbeschaffenheit: und Empfindlichkeit sind von geringerer Bedeutung, Stauung uberhaupt nicht. Anzahl und Kombination pathologischer Kriterien sind bedeutsam.

Gallesedimentcytologie: Eine neue, nichtinvasive Methode im postoperativen Monitoring nach Lebertransplantation

Die Ergebnisse der Lebertransplantation werden nicht nur von der Organqualitat, dem Zustand des Empfangers sowie der Transplantation selbst, sondern auch wesentlich durch den fruhpostoperativen Verlauf beeinflust. Ein kontinuierliches und intensives Monitoring wahrend dieser Phase ist von besonderer Bedeutung. Bei routinemasig eingelegtem T-Drain stellt die Galle als direktes Produkt des Transplantates ein leicht zugangliches Medium zur Beurteilung der Transplantatfunktion dar. Bisher werden Volumen und Farbe der Galle bei der klinischen Beurteilung berucksichtigt. In dieser Arbeit werden die Eignung der Galle fur ein cytologisches Monitoring untersucht und erste Ergebnisse vorgestellt.