H. Keck

Technique and results of biliary reconstruction using side-to-side choledochocholedochostomy in 300 orthotopic liver transplants

ObjectiveThe authors evaluated the complication rate and outcome of side-to-side common bile duct anastomosis after human orthotopic liver transplantation. Summary Background DataEarly and late biliary tract complications after orthotopic liver transplantation remain a serious problem, leading to increased morbidity and mortality. Commonly performed techniques are the end-to-end choledochocholedochostomy and the choledochojejunostomy. Both techniques are known to coincide with a high incidence of leakage and stenosis of the bile duct anastomosis. The side-to-side bile duct anastomosis has been shown experimentally to be superior to the end-to-end anastomosis. The authors present the results of 316 human liver transplants, in which a side-to-side choledochocholedochostomy was performed. MethodsBiliary tract complications of 370 transplants in 340 patients were evaluated. Three hundred patients received primary liver transplants with side-to-side anastomosis of donor and recipient common bile duct. Thirty-two patients with biliary tract pathology received a bilioenteric anastomosis, and in eight patients, side-to-side anastomosis was not performed for various reasons. Clinical and laboratory investigations were carried out at prospectively fixed time points. X-ray cholangiography was performed routinely in all patients on postoperative days (PODs) 5 and 42. In patients with suspected papillary stenosis, endoscopic retrograde cholangioscopy and papillotomy were performed. ResultsOne biliary leakage (0.3%) was observed within the early postoperative period (PODs 0 through 30) after liver transplantation. No stenosis of the common bile duct anastomosis was observed during this time. Late biliary stenosis occurred in two patients (0.6%). T tube-related complications were observed in 4 of 300 primary transplants (1.3%). Complications unrelated to the surgical technique, including papillary stenosis (5.7%) and ischemic-type biliary lesion (3.0%), which must be considered more serious in nature than complications of the anastomosis or T tube-related complications, were observed. Papillary stenosis led to frequent endoscopic interventions and retransplantations in 1.3%.

Orthotopic liver transplantation after extended bile duct resection as treatment of hilar cholangiocarcinoma First long‐terms results

Abstract Although the surgical treatment of hilar cholangiocarcinoma represents the only potentially curative option, survival figures remain low over the long term. After hilar and partial hepatic resections for hilar cholangiocarcinoma, loco‐regional tumor recurrence appears as the primary site of failure. From April 1992 to April 1996, 14 patients underwent extended bile duct resections. Extended bile duct resections combine total hepatectomy, partial pancreatoduodenectomy, and liver transplantation in an attempt to eradicate the entire biliary tract without dissecting the hepatoduodenal ligament. The postoperative 60‐day mortality rate was 14% (n= 2). The rate of curative resections was 93% (13 of 14 extended bile duct resections). One‐ and 4‐year survival rates after curative resections were 56% and 30%, respectively. The rate of curative resections increased by combining total hepatectomy, partial pancreatoduodenectomy, and liver transplantation, i.e., extended bile duct resection. However, survival figures have not improved accordingly. Therefore, this extended surgical procedure has to be implemented with caution and possibly not without modifications (e.g., multimodal treatment).

Orthotopic liver transplantation after extended bile duct resection as treatment of hilar cholangiocarcinoma

Abstract Although the surgical treatment of hilar cholangiocarcinoma represents the only potentially curative option, survival figures remain low over the long term. After hilar and partial hepatic resections for hilar cholangiocarcinoma, locoregional tumor recurrence appears as the primary site of failure. From April 1992 to April 1996, 14 patients underwent extended bile duct resections. Extended bile duct resections combine total hepatectomy, partial pancreatoduodenectomy, and liver transplantation in an attempt to eradicate the entire biliary tract without dissecting the hepatoduodenal ligament. The postoperative 60-day mortality rate was 14% (n = 2).The rate of curative resections was 93% (13 of 14 extended bile duct resections). One- and 4-year survival rates after curative resections were 56% and 30%, respectively. The rate of curative resections increased by combining total hepatectomy, partial pancreatoduodenectomy, and liver transplantation, i. e., extended bile duct resection. However, survival figures have not improved accordingly. Therefore, this extended surgical procedure has to be implemented with caution and possibly not without modifications (e. g., multimodal treatment).

Experience with cuff rearterialization in 600 orthotopic liver grafts in the rat

The model of orthotopic rat liver transplantation has been a useful tool in transplantation research for two decades. Due to technical problems, the optional hepatic artery anastomosis is not performed in many experiments. Recently developed techniques, however, have made rearterialization a simple procedure. With our technique of cuff rearterialization to the recipient common hepatic artery, in 600 rat liver grafts we achieved high viability, and an early patency rate of 100%. Patency rates after 2 and 21 days were nearly 90%. Cuff rearterialization is simple, rapid to perform, and provides a physiologic model. Compared to strictly venous liver grafts, rearterialized grafts demonstrate improvement in survival, more rapid normalization of liver function parameters, a better preserved liver structure, and less biliary complications. Rearterialization is an important component of a physiologically relevant rat liver transplantation model, and non-specific changes due to arterial ischemia may adversely affect the interpretation of experimental data.

Mycobacterial infection after liver transplantation

Tuberculosis occurred in 5 (1.2%) of 462 liver transplant recipients. De novo infection was assumed in 4 patients and a recurrent infection in 1. The clinical courses varied, from asymptomatic open lung tuberculosis to disseminated disease with cerebral tuberculoma and convulsions. Four patients survived with anti-tuberculous triple-drug therapy. Very few cases of tuberculosis after liver transplantation have been reported (4 patients in the medical literature and 5 patients in this paper). However, the incidence, course of infection, and outcome seem to be similar to those of tuberculosis in renal transplant recipients, approximately 150 cases of which are known.ZusammenfassungBei 5 von 462 Patienten (1,2%) trat nach Lebertransplantation Tuberkulose auf. In einem Fall wurde Reinfektion, in 4 Fällen Neuinfektion angenommen. Die klinischen Verläufe waren sehr unterschiedlich: von asymptomatischer offener Lungentuberkulose bis zu disseminierter Erkrankung mit zerebralem Tuberkulom und Konvulsionen. Nach antituberkulöser Tripelmedikamententherapie überlebten 4 Patienten. Es wurde bisher über nur sehr wenige Tuberkulosefälle nach Lebertransplantation berichtet: in der Medizinliteratur über 4 Fälle and in der hier vorgelegten Untersuchung über 5. Dennoch ist anzunehmen, daß Häufigkeit, Verlauf and Ausgang einer Tuberkuloseinfektion nach Lebertransplantationen ähnlich sind wie nach Nierentransplantationen, bei denen etwa 150 Fälle erfaßt wurden.

Fungal infections in liver transplant recipients

ZusammenfassungUm Inzidenz, Risikofaktoren, klinischen Verlauf und Prognose von Pilzinfektionen nach Lebertransplantation zu klären, wurden die Verläufe von 462 Patienten retrospektiv untersucht, die zwischen Oktober 1988 und Februar 1994 konsekutiv transplantiert wurden. Bei 13 unserer Patienten (2,8%) beobachteten wir Infektionen mit Aspergillus (6mal), Candida (5mal), Mucor (1mal) und Cryptococcus (1mal) Dabei trat die Infektion bei 12 der 13 Patienten bereits während der ersten 2 postoperativen Monate auf. Von den von anderen Autoren beschriebenen potentiellen Risikofaktoren (Alter, Abstoßungsbehandlung, Dialyse, maschinelle Beatmung, Graftversagen, lange Operationszeit, Retransplantation, schwere Allgemeininfektion) korrelierte bei unseren Patienten keine einzige mit den Infektionen. Allerdings war die Inzidenz der Pilzinfektionen bei Patienten, die 3 oder mehr dieser Risikofaktoren zeigten, signifikant erhöht (p<0,001). Ferner traten 6 von 7 exogenen Infektionen (Aspergillus, Mucor) vor dem Umzug unserer Transplantationsstation aus dem 1. Stock eines alten, efeubewachsenen Ziegelbaus in den 7. Stock eines Neubaus im Juli 1991 auf (p=0,01). Dies zeigt, daß die Exposition die Inzidenz von Pilzinfektionen nach Lebertransplantation wesentlich beeinflußt. Daraus folgt, daß insbesondere schwer kompromittierte Patienten einer strengen Expositionsprophylaxe unterzogen wurden müssen, um Infektionen mit Aspelgillus/Mucor zu vermeiden, die bei unseren Patienten eine Letalität von 57% aufwiesen. Bei 5 Patienten beobachteten wir Candidainfektionen als pathologisches Überwuchern der oralen Standortflora in Trachea und/oder Speiseröhre, die unter Therapie ausnahmslos ausheilten.AbstractA retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious nonfungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P<0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P=0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.

Incidence and outcome of arterial complications after orthotopic liver transplantation

Abstract  Arterial complications can be a major factor in morbidity and mortality after orthotopic liver transplantation (OLT), as they may cause graft failure, sepsis and complications of the biliary tract. From September 1988 to December 1994, 571 OLT were performed in 529 patients. The follow‐up period ranged from 8 to 83 months. Actuarial 1–, 3– and 5‐year survival figures were 91 %, 87 % and 85 %, respectively. In 12 cases (2.1 %) complications of the arterial anastomoses were observed. Early arterial complications occurred in eight cases from various causes, while late arterial complications were exclusively Thromboses and developed in four patients 8, 12, 26 and 37 months after surgery, respectively. The main clinical course in patients with arterial thromboses was septic cholan‐gitis with destruction of the biliary tree. Although 70% of the grafts with arterial thrombosis were lost, 30 % could, at least temporarily, be salvaged by other treatment options. Provided adequate treatment is carried out, arterial complications do not affect overall patient survival.

Selection of small hepatocellular carcinoma improves long‐term results of hepatic transplantation for malignancy

Abstract Liver transplantation for advanced hepatocellular carcinoma is often followed by early tumour recurrence and death. At the beginning of the liver transplantation programme at Berlin Virchow we decided to offer liver transplantation only to patients with solitary tumours not exceeding a maximum diameter of 5 cm or to patients with two or three tumour nodes with a maximum diameter of 4 cm. From September 1988 to October 1993 435 liver transplants were performed in 403 patients. Of these, 32 patients (8 %) had a histologically confirmed hepatocellular carcinoma (29 males, 3 females, median age 56 years). The overall actuarial survival according to Kaplan‐Meier for the whole series of 32 patients with hepatocellular carcinoma was 82%, 78%, and 78% at 1, 2 and 3 years, respectively. Tumour size alone did not seem to be a relevant factor when comparing patients with tumours up to or larger than 3 cm in diameter. Patients with solitary tumours had a better prognosis than patients with multiple tumours. The largest difference was found between patients with stage I‐III (UICC) tumours and those with stage IVA tumours: 1‐, 2‐ and 3‐year survival rates were 89% throughout in the former group, while the corresponding figures for patients with stage IVA tumours were 63%, 47% and 47%. Efforts should be made to identify stage IVA tumours preoperatively in order to use the precious resource of scarce donor livers in an optimal way.

Donor criteria in hepatic transplantation

ZusammenfassungNach 201 Lebertransplantationen von September 1988 bis November 1991 wurde retrospektiv der Postischämieschaden bei Vorliegen verschiedener Spenderkriterien untersucht. Als Kriterien galten die Hospitalisierungszeit auf Intensivstation vor Organentnahme, die Todesursache Bowie allgemein als kritisch eingeschätzte Parameter wie hypotensive Kreislaufphasen (n = 69; 34,4%), kardiopulmonale Reanimation (n = 20; 9,9%), erhöhte Serumtransaminasen (s-AT) (n = 11; 5,5%) oder ein Alter über 50 Jahre (n = 16; 8,0%). 91 Organspender lagen weniger als 24 h auf einer Intensivstation, hingegen 29 Spender (14,4%) 4–6 Tage und 14 Spender (7,0%) länger als 6 Tage. Häufigste Todesursachen waren Subarachnoidalblutungen (n = 70; 34,8%), isolierte Schädel-Hirn-Traumen (n = 68; 33,8%) und Polytraumen (n = 33; 16,4%). Der Postischamieschaden wurde anhand der maximalen postoperativen s-AT sowie der Inzidenz eines primären Transplantatversagens (PNF) oder einer schweren, reversiblen Transplantatschädigung (s-AT > 2000 IU/I) abgeschätzt. Maximale s-AT, Alter der Organspender und -empfänger sowie kalte Ischämiezeiten unterschieden sich zwischen den einzelnen Gruppen nicht signifikant. Schwere reversible Schäden zeigten 14 Transplantatlebern (7,0%); eine PNF trat in 5 Fallen (2,5%) auf, die erfolgreich einer frühen Retransplantation unterzogen wurden. Spenderkriterien waren in beiden Gruppen mit ähnlicher Häufigkeit wie im Gesamtkollektiv vertreten. Maximale s-AT bei Transplantatversagen (GOT: 4944 ± 2280 IU/I; GPT: 3186 ± 19181U/I) lagen signifikant (p > 0,01) höher als bei primärer Transplantatfunktion (GOT: 699 ± 935 IU/I; GPT: 620 ± 701 IU/I). Diese Ergebnisse sind trotz eines hohen Anteils bislang als kritisch angesehener Spender Ausdruck einer vermutlich zu strengen Selektion. Eine vorsichtige Lockerung der Selektionskriterien erscheint daher gerechtfertigt.AbstractThe early outcome of 201 liver grafts transplanted consecutively between September 1988 and November 1991 was investigated retrospectively. Donors were categorized according to their hospitalization periods in an intensive care unit (ICU) prior to harvesting, their causes of death, and the variables generally believed to be critical in liver donation, such as arterial hypotension (n = 69; 34.3 %), cardiopulmonary resuscitation (n = 20; 9.9%), elevated serum-aminotransferases (s-AT) (n = 11; 5.5%), or an age over 50 years (n = 16; 8.0 %). Ninety-one donors (45.3 %) spent less than 24 h in an ICU; 29 donors (14.4%) and 14 donors (7.0%) had hospitalization periods generally considered critical of 4–6 days and more than 6 days, respectively. The most common causes of death were subarachnoidal bleeding (n = 70; 34.8%), isolated head injuries (n = 68; 33.8%), and polytraumata (n = 33; 16.4%).The postischemic hepatocellular damage was evaluated comparing peak post-transplant s-AT, which did not differ significantly between groups; nor did donor and recipient ages or cold ischemia times. Fourteen grafts (7.0%) showed a reversible preservation injury presenting with post-transplant s-AT elevated above 2000 IU/I. Five cases (2.5%) of a primary non-functioning graft (PNF) underwent early retransplantation successfully. Serum-aminotransferases (AST: 4944 ± 2280 IU/I; ALT: 3186 ± 1918 IU/ I) were significantly (P < 0.01) elevated as compared to primary functioning grafts (AST: 699 ± 935 IU/I; ALT: 620 ± 701 IU/I). The donor structure of both groups reflected the distribution of variables in the entire collective. No significant overrepresentations were observed. These results indicate that in the past criteria for donor selection have probably been applied too stringently. To determine true limits the pool of liver donors should carefully be extended.

The importance of late infections for the long-term outcome after liver transplantation

Abstract  We investigated the late infections of 400 consecutive liver transplantations performed in 368 patients. After a mean follow‐up of 45 months, a total of 180 late infections occurred in 110 liver recipients. Frequent agents were CMV, entero‐coccus, candida and staphylococcus. Pneumonia was the most dangerous late infection with a high mortality rate. Late infections were responsible for ten deaths that were all caused by atypical pneumonia. The majority of late infections appeared during the first year after liver transplantation. Thereafter, the risk of infection declined significantly.