[Perihilar cholangiocarcinoma (Klatskin tumor)]. / Zentrales Gallengangskarzinom (Klatskin-Tumor).

Perihilar cholangiocarcinoma or Klatskin tumors are a rare entity arising from the extrahepatic bile duct bifurcation. Considering the close anatomical relationship of the bile duct bifurcation with the portal vein bifurcation and hepatic arteries, surgical treatment is demanding. With an incidence of only 2-4 cases/100,000 population/year patients should be referred to a specialized center. The tumors are usually poorly differentiated adenocarcinomas growing diffusely along the duct and also the perineural sheath. Only radical surgery offers a curative option and currently surgical strategy usually consists of en bloc resection of the bile duct, extended liver resection and portal vein resection. Proximal and lateral safety margin R0 resections are technically very demanding procedures because of the local anatomy.

[Importance of graft arterialization in rat liver transplantation]. / Bedeutung der Arterialisation des Transplantates bei Rattenlebertransplantation.

68 LEW-livers were grafted orthotopically into LEW; 18 with and 50 without rearterialization of the graft. 73.3% of the recipients without arterialization died of ischemic damage of the donor livers and bile ducts. The other animals survived indefinitely (more than 120 days). However, 73.3% of the recipients with graft arterialization survived more than 120 days, three animals 8-23 days. Only one recipient died of bile duct complications on the first postoperative day. These results suggest the importance of graft arterialization in rat liver transplantation, despite the observation that all untreated animals survive after complete dissection of the arterial blood flow to liver. Intraoperatively rats can tolerate acute occlusion of portal vein and vena cava inferior up to 50 min without any bypass for the decompression of splanchnic blood flow. We examined the formation of arterial collateral blood supply in the dearterialized livers by application of gelatin-medium. On day 3 we observed collateral vessels in the hilus of dearterialized livers which mainly originated from the gastroduodenal region and were connected to the remaining arterial system of the liver. Complete arterialization was shown on day 7. In the hepatic graft without arterialization the arterial collaterals were not seen until day 7, and complete arterial blood flow was demonstrated after three postoperative weeks.

[Immunologic mechanism following liver transplantation. An experimental study in the rat]. / Immunmechanismus nach Lebertransplantation. Experimentelle Studie bei Ratten.

To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialization of the grafts was achieved with an hepatico aortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67% (n = 12), WiS- in 60% (n = 20) and BUF- in 43% (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 +/- 1.3 d (control: 6.5 +/- 0.5 d; P less than 0.001), at 10 days treatment 15.3 +/- 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90% and the ConA-stimulation of LEW spleen cells in more than 95%. In MLC LP showed strong inhibitory effect (inhibition rate greater than 97%) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 +/- 0.5 d). We therefore can conclude that the cellular immunosurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (greater than 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 +/- 3.4 d, control 6.2 +/- 1.0 d; P less than 0.001). Lymphoid cell transfer (1 X 10(8)) did did not result in significant prolongation of survival time (8.0 +/- 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.

[Immunosuppressive and cytotoxic effect of the humoral factors from ischemic damaged organs (author's transl)]. / Immunosuppressiver und zytotoxischer Effekt des humoralen Faktors ischämisch geschädigter Organe.

These studies demonstrate the presence of an immunosuppressive and cytotoxic factor in the perfusate of ischemic damaged liver. A BDE rat liver perfusate (LP) was prepared after 6 h warm ischemia by intraportal perfusion with 2 ml/g of Ringer's solution (one time-LP1 or five times-LP5 with the same volume of solution). Protein amount of LP1 and LP5 was 0.9 and 2.8-3.9 mg/ml. In vivo activity of the hepatic perfusates was studied by effect on renal allograft survival time. LEW rats with BDE kidney transplant, treated daily with 2 ml of LP1 for 5 days, starting on the day of grafting, survived 8.9 +/- 1.8 days, significantly longer than control animals (6.5 +/- 0.5 days). After administration of LP5 renal recipients survived 10.3 +/- 1.3 days and when the treatment with LP5 was prolonged to 10 days animals survived 9-34 days (mean 15.3 +/- 7.3 days). The presence of the suppressive factor was also studied in renal, spleen and heart extracts, prepared after 6 h warm ischemia. Protein amount of extracts was adjusted to 3-4 mg/ml by Ringer's solution. Immunosuppressive activity of LP and other organ extracts was tested in vitro by their influence on MLC reaction (LEW and BDE lymphocytes) and on LEW cells in the PHA stimulation assay. Lymphocyte blastogenic response on MLC reaction and in culture with PHA was strongly inhibited by LP but weakly by organ extracts. Hepatic perfusates were cytotoxic against lymphocytes and fibroblasts in a three day cultures. Cytotoxic activity of the organ extracts was lower than LP. Extract of the cold preserved kidneys showed immunosuppressive and cytotoxic effect like extract of ischemically injured kidneys but smaller than LP. After heat inactivation at 70 degrees C the activity of hepatic perfusate decreased. Immunosuppressive organ factor (IOF) seems to be a normal cell component, not a decomposition product of the ischemically damaged hepatic tissue.

[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. / Verlängerung der Ischämietoleranzzeit der Spenderleber durch alkalinisierte Konservierungslösungen.

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.

[Ex situ operation on the liver. A new possibility in liver surgery]. / Ex situ Operation an der Leber. Eine neue Möglichkeit in der Leberchirurgie.

A method for an ex situ operation of the liver is presented with the example of such an operation in a 40-year-old patient. With this operation bilateral liver metastases of a leiomyosarcoma--which were otherwise regarded as irresectable--were resected. Function of the liver after reimplantation was good. Liver protection was performed by perfusion with cardioplegic HTK-solution (Bretschneider). The techniques of liver ex- and implantation are based on the methods of liver transplantation. Extracorporal femoro-porto-axillary bypass for decompression of the inferior caval vein and portal vein was used throughout the anhepatic period of 6 h. It is supposed that the method described here--which according to the authors' knowledge has been performed for the first time in a patient--will open up new perspectives for the surgery of malignant and occasionally of benign tumors, if necessary also for other surgical liver diseases. As an additional possibility, in situ protection of the liver with consecutive operation of the bloodless liver in situ is discussed. This procedure will correspond for the most part to the ex situ technique described here.