F. W. Eigler

Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation

Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidinetryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data preand post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15h (n=7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15h.

Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation. A prospective, randomized study.

Abstract Over a 30‐month period, 60 patients (30 in each group) suffering from end‐stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidine‐tryptophan‐ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data pre‐and post‐transplantation, as well as follow‐up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15 h (n= 7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15 h.

Evidence for increased nitric oxide production after liver transplantation in humans.

To evaluate the role of in vivo-produced nitric oxide (NO) after orthotopic liver transplantation, nitrate, a stable end product of spontaneous NO conversion in blood, was assayed in plasma samples of 32 patients. In 31 patients, nitrate increased from 36±2 μM to 137±8 μM within the first 6 postoperative days. In 11 out of 12 patients with an uneventful early postoperative course, nitrate increased from 33 ±2 μM to 70 ±8 μM, and returned to baseline levels within 2–3 days. In the remaining 20 patients with episodes of rejection and/or infection, the nitrate peak was augmented and prolonged. Ten patients suffering from these events in the later postoperative course showed a second nitrate elevation. In 31 patients, effective plasma levels of cyclosporine were reached 4–5 days after OLT. The patient without significant elevation in plasma nitrate had effective levels already at day 1. After liver resection or coronary bypass grafting, the median nitrate level remained at 21 μM (range 15–36 μM; healthy persons: median 24 μM, range 18–32 μM). After kidney transplantation nitrate was elevated in the early postoperative course. Thus, NO formation appears to be increased after solid organ transplantation, but not after other surgeries. After OLT, the increase appears to occur (a) in response to rejection and/or infection, and (b) 4–6 days after surgery in the absence of overt complications. In the latter case, NO might be involved in subclinical rejection and its production is possibly dependent upon the effectiveness of the immunosup-pressive therapy.

Impact of colour Doppler sonography on detection of thrombosis of the hepatic artery and the portal vein after liver transplantation

Sixty patients who received 75 consecutive liver grafts and had routine Doppler sonography monitoring in the early postoperative period (three times a day) were reviewed for vascular complications. Thrombosis of the hepatic artery was detected in seven patients (3, 4, 20, 24, 48, 70 and 84 h after liver transplantation) and was then confirmed by emergency laparotomy in six cases. In one patient, thrombosis was verified by angiography before laparotomy. In two patients thrombectomy was successful, in five patients retransplantation had to be performed. Portal vein occlusion was detected in three patients (24, 26 and 90 h after transplantation) and all were successfully treated by thrombectomy and partial arterialization of the portal vein. Colour Doppler sonography was associated with no false-positive or -negative results. The specificity was 100% for the diagnosis of hepatic artery and portal vein thrombosis. In our opinion colour Doppler sonography will be able to replace time-consuming angiography in vascular diagnostics in the early postoperative phase after liver transplantation. Furthermore, there is evidence that frequent use of this non-invasive technique permits early detection of clinically unsuspected vascular complications and subsequent immediate relaparotomy, which is linked to a reduction in the rate of retransplantation.ZusammenfassungBei 60 Patienten nach Lebertransplantation (75 Transplantate) wurde in der ersten postoperativen Woche dreimal täglich eine farbcodierte Dopplersonographie zum Ausschluβ vaskulärer Komplikationen durchgeführt. Eine Thrombose der Leberarterie wurde bei 7 Patienten diagnostiziert (3, 4, 20, 24, 48, 70 und 84 h nach der Transplantation). Die Diagnose wurde intraoperativ bei Relaparotomie bestätigt, bei einem Patienten erfolgte vor der Revisionsoperation eine Angiographie. Zweimal war eine Thrombektomie der Leberarterie erfolgreich, bei fünf Patienten muβte retransplantiert werden. Eine Pfortaderthrombose wurde bei drei Patienten (24, 26 und 90 h nach der Transplantation) diagnostiziert. Immer war eine Thrombektomie mit partieller Arterialisierung der Pfortader erfolgreich. Falsch negative bzw. falsch positive Befunde wurden nicht erhoben, so daβ die farbcodierte Dopplersonographie mit einer hohen Sensitivität bei einer Spezifität von 100% in der Diagnose von Gefäßkomplikationen nach Lebertransplantation verbunden ist. In der Diagnostik von Gefäßkomplikationen während der frühen postoperativen Phase nach Lebertransplantationen kann die Angiographie durch die farbcodierte Dopplersonographie ersetzt werden. Die Diagnose insbesondere von klinisch noch nicht manifesten Gefäßkomplikationen ist durch engmaschigen Einsatz der Methode möglich und kann durch frühzeitige Relaparotomie zu einer Senkung der Retransplantationsrate führen.

Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation: a case report

We discuss the case of a 30-year-old primipara woman who developed a liver rupture as a complication of the HELLP syndrome. A liver necrosis and bleeding made a hepatectomy necessary. A portocaval shunt was able to maintain the patient until she underwent urgent liver transplantation. In an excellent state of recovery, the woman and her baby were discharged from the hospital 66 days after having been admitted.

Monitoring of soluble HLA class I size variants after liver transplantation.

To monitor soluble HLA class I (sHLA-I) and their size variants after liver transplantation (LTX) plasma samples from 22 LTX patients were studied by sHLA-I ELISA, SDS-PAGE, and densitometry. Samples collected were classified into three groups: Group 1 comprised samples taken during episodes without complications, group 2 during episodes of cholangitis/cholestasis (CC), and group 3 during episodes of acute rejection (AR). Compared to group 1 (0.27 +/- 0.03 SEM microg/ml) mean sHLA-I increments in groups 2 and 3 were with 0.53 +/- 0.05 SEM microg/ml and 0.47 +/- 0.04 SEM microg/ml increased (p < 0.001). The same samples were studied by SDS-PAGE and the 43, 39, and 35 kD sHLA-I variants were quantified densitometrically. In samples of group 1 ratios of 43 vs. 39 kD bands revealed a mean of 2.1 +/- 0.3, whereas in group 2 and 3 these were only 0.8 +/- 0.1 SEM and 0.9 +/- 0.1 SEM, respectively, (p < 0.001). For the relation between 43 and 35 kD variants a reduced ratio of 1.1 +/- 0.2 SEM was confined to group 3 samples (p < 0.001), as groups 1 and 2 had ratios of 13.4 +/- 2.3 SEM and 8.4 +/- 2.9 SEM, respectively. This indicates that elevated sHLA-I levels during CC or AR are mainly caused by increases of 39 and/or 35 kD sized molecules. Therefore, our study demonstrates, that after LTX the contribution of sHLA-I size variants to total sHLA-I amounts changes drastically during immune activation pointing to different mechanisms of sHLA-I release.

Nonparenchymal cell and hepatocellular injury to human liver grafls assessed by enzyme-release into the perfusate

Experimental studies have demonstrated preferential injury to the sinusoidal endothelium during liver preservation with University of Wisconsin (UW) or Euro-Collins solution. This endothelial cell injury has an unclear pathogenesis, and it has not yet been studied in the human liver. Therefore, we analyzed the effluent of 21 human liver allografts after cold storage. Markers of hepatocellular and nonparenchymal cell injury were assessed. After preservation with UW solution, early effluent samples contained 1823 ± 1494 U/1 lactate dehydrogenase (LDH), 493±516 U/1 alanine aminotransferase (ALT) and 132±97 U/1 creatine kinase (CK; 92±92 U/1 CK-BB). The effluent of livers preserved in histidine-tryptophan-ketoglutarate (HTK) solution contained 3681±2009 U/1 LDH, 1139±599 U/1 ALT and 282±120 U/1 CK (165±91 U/1 CK-BB). Comparison of effluent enzyme activities with liver tissue enzyme activities indicates that the release of the endothelial cell/nonparenchymal cell marker creatine kinase was higher, by a factor of 7–8, than the release of hepatocellular enzymes. Effluent thrombomodulin concentrations were 123±248 ng/ml (UW) and 604±299 ng/ml (HTK), and effluent glucose concentrations, 40.3± 27.0 mM (726±486 mg/dl; UW) and 10.4±4.5 mM (187 ±81 mg/dl; HTK). We conclude that prominent endothelial cell injury also occurs in human liver grafts after preservation with UW solution or HTK solution. This endothelial cell injury is unlikely to be caused by hypoxia-induced energy deficiency, as it affects a cell type with a high glycolytic capacity in the presence of high glucose levels. Determination of enzyme activities in the easily obtained effluent of liver grafts might constitute an additional parameter for the assessment of graft “quality” prior to transplantation.ZusammenfassungExperimentelle Untersuchungen an der Ratte zeigten in verschiedenen Studien eine bevorzugte Endothelzellschädigung bei der kalten Konservierung der Leber nit University-of-Wisconsin-Lösung (UW) oder Euro-Collins-Lösung. Diese Endothelzellschädigung unklarer Pathogenese wurde bislang noch nicht an der humanen Leber untersucht. Deshalb bestimmten wir Marker der hepatozellularen Schadigung und der Nichtparenchymzellschddigung im Effluat von 21 humanen Transplantatlebern nach der kalten Lagerung. Nach Konservierung der Leber nit UW-L6sung enthielten frühe Proben des Effluats 1823 ± 1494 U/1 Lactatdehydrogenase (LDH), 493 ± 516 U/1 Alaninaminotransferase (ALT) und 132±97 U/1 Kreatinkinase (CK; 92±92 U/1 CK-BB). Das Effluat der nit Histidin-Tryptophan-Ketoglutarat-Lösung (HTK) konservierten Lebern enthielt 3681±2009 U/1 LDH, 1139±599 U/1 ALT and 282± 120 U/1 CK (165 +91 U/1 CK-BB). Der Vergleich der im Effluat gemessenen Enzymaktivitäten nit den im Lebergewebe vorhandenen Enzymaktivitaten deutet darauf hin, daß die Freisetzung des Endothelzell-/Nichtparenchymzellmarkers Kreatinkinase um den Faktor 7- bis 8mal hoher ist als die Freisetzung hepatozelluldrer Enzyme. Die. Thrombomodulinkonzentrationen im Effluat betrugen 123±248 ng/ml (UW) und 604±299 ng/ml (HTK). Die Glukosekonzentrationen im Effluat lagen bei 40,3±27,0 mM (726 ±486 mg/dl; UW) und 10,4±4,5 mM (187±81 mg/dl; HTK). Zusammengenommen zeigen these Ergebnisse, daß auch bei der Konservierung humaner Lebern nit UW- oder HTK-Lösung eine deutliche Endothelzellschädigung auftritt. Diese Endothelzellschädigung läßt sich schwerlich durch hypoxiebedingten Energiemangel erklären, da she —in Gegenwart hoher Glukosespiegel — einen Zelltyp nit hoher glykolytischer Kapazitdt betrifft. Die Bestimmung der hepatozellulären Enzymaktivitäten im leicht zu gewinnenden Effluat von Transplantatlebern könnte einen zusätzlichen Parameter zur Einschdtzung der “Transplan-tatqualität” vor der Transplantation darstellen.

Injury to hepatocytes and non-parenchymal cells during the preservation of human livers with UW or HTK solution: a determination of hepatocellular enzymes in the effluent perfusate for preoperative evaluation of the transplant quality

Abstract  In 50 livers harvested for transplantation, injury was assessed by determination of the enzymes in the effluent perfusate after cold ischemia. The results were compared to the histology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury did neither correlate with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes in the perfusate did indicate preexisting damage of the liver even when the biopsy showed normal liver tissue. Of 12 livers with high activity of hepatocellular enzymes in the effluent (activity of more than twice the median), 7 showed delayed onset of function or a primary non‐function. In the other 38 livers with an enzyme activity below this borderline no delayed function or primary non‐function was observed. Because of additional influences a prognosis of the function after transplantation was not possible, but the determination of the enzymes in the effluent of marginal livers probably allows the preoperative recognition of organs which will do well.

Eine neue Technik zur Wiederherstellung des gemeinsamen Gallengangs nach schwerer Schädigung durch eine laparoskopische Cholezystektomie

Schwere Gallengangsverletzungen sind nach laparoskopischen haufiger als nach konventionellen Cholezystektomien zu beklagen. Sie resultieren meist aus technischen Problemen oder unzureichender Identifikation der entsprechenden Strukturen. Das sofortige Erkennen der Gallengangsverletzung ist fur eine entsprechende Therapie ebenso wichtig wie die adequate chirurgische Technik, die angewendet wird. Hier wird eine neue Methode der Gallenwegrekonstruktion unter Verwendung eines Jejunalkonduits vorgestellt. Das Verfahren wurde bislang bei 5 Patienten mit schweren Gallengangsverletzungen (Typ 3 and 4 nach Bismuth) [2] nach laparoskopischer Cholezystektomie erfolgreich angewendet. Der Verlauf nach nunmehr 9 Monaten bis zu mehr als 2 Jahren war ohne Probleme and vielversprechend. Die Methode der Anwendung des Jejunalkonduits erscheint uns zur Rekonstruktion bei schweren Gallengangverletzungen sehr empfehlenswert.Laparoscopic cholecystectomy involves a higher incidence of severe common bile duct injury than did open cholecystectomy. The severe injuries most often result from technical problems and inadequate exposure. Reconstruction of the bile duct is then possible provided that an immediate diagnosis is made and an appropriate surgical technique is applied. The report focuses on a new method of reconstruction of the common bile duct by interposition of a small jejunal conduit. The procedure was performed in five patients with severe bile duct injury (Bismuth class 3–4) that occurred during laparoscopic cholecystectomy. The outcome after follow-up periods of 9 months to more than 2 years is promising. This method of reconstruction is therefore recommended for severe forms of bile duct injury.ZusammenfassungSchwere Gallengangsverletzungen sind nach laparoskopischen häufiger als nach konventionellen Cholezystektomien zu beklagen. Sie resultieren meist aus technischen Problemen oder unzureichender Identifikation der entsprechenden Strukturen. Das sofortige Erkennen der Gallengangsverletzung ist fur eine entsprechende Therapie ebenso wichtig wie die ädequate chirurgische Technik, die angewendet wird. Hier wird eine neue Methode der Gallenwegrekonstruktion unter Verwendung eines Jejunalkonduits vorgestellt. Das Verfahren wurde bislang bei 5 Patienten mit schweren Gallengangsverletzungen (Typ 3 and 4 nach Bismuth) [2] nach laparoskopischer Cholezystektomie erfolgreich angewendet. Der Verlauf nach nunmehr 9 Monaten bis zu mehr als 2 Jahren war ohne Probleme and vielversprechend. Die Methode der Anwendung des Jejunalkonduits erscheint uns zur Rekonstruktion bei schweren Gallengangverletzungen sehr empfehlenswert.

The achievement of surgery in the overall therapy plan in Crohn disease

The analysis of 205 prospectively investigated patients with Crohns disease under conservative (112) and operative (93) treatment with essentially comparable distribution of age and duration of the disease resulted in a significantly better outcome of the operated patients judging by the time free of recurrencies and the frequency of recurrencies for the localisation of ileocolitis and colitis. In ileitis, however, the results are nearly equal for both groups. The results warrant a more liberal indication for operation especially in those patients with involved colon.SummaryThe analysis of 205 prospectively investigated patients with Crohns disease under conservative (112) and operative (93) treatment with essentially comparable distribution of age and duration of the disease resulted in a significantly better outcome of the operated patients judging by the time free of recurrencies and the frequency of recurrencies for the localisation of ileocolitis and colitis. In ileitis, however, the results are nearly equal for both groups. The results warrant a more liberal indication for operation especially in those patients with involved colon.ZusammenfassungDie Analyse von 205 prospektiv betreuten Kranken mit M. Crohn unter konservativer (112) und operativer (93) Therapie mit im wesentlichen gleicher Verteilung von Alter und Krankheitsdauer ergab ein eindeutig günstigeres Abschneiden den Operierten gemessen an der Rezidivfreiheit und der Rezidivhäufigkeit für die Lokalisation Ileocolitis und Colitis. Bei der Ileitis wurden für beide Gruppen etwa gleich gute Resultate erzielt. Die Ergebnisse rechtfertigen eine großzügigere Indikationsstellung zur Operation, jedenfalls wenn bei den Kranken das Colon mitbefallen ist.