Tolerance by old livers of prolonged periods of preservation in the rat.

To determine the tolerance of old livers to prolonged preservation, livers from aged rats (corresponding to humans in the sixth to seventh decades of life) were transplanted after specific periods of cold preservation. Male BN/BiRij rats received orthotopic, arterialized liver grafts from either young (5 months) or old (25 to 28 month) donor rats after liver storage for 12 (n = 6), 24 (n = 6) or 30 (n = 10) hours in University of Wisconsin solution. Outcome was assessed by survival, liver enzymes after transplantation, and histology of the grafts. There were no significant differences in survival rates between recipients of old and young grafts. All rats survived after 12-hr and 24-hr preservation except one recipient of an old graft preserved for 24 hr. After 30-hr preservation recipients of old and young livers had identical survival rates (60%). There was a strong correlation between the highest postoperative AST and ALT and the duration of preservation in all groups (P < 0.0001), but only in the 24-hr preservation experiments was the ALT significantly higher in recipients of old grafts than in recipients of young livers (P = 0.025). Age of the donor did not significantly affect the peak AST, but there was a correlation between donor age and the highest postoperative ALT (P = 0.007). Although intracellular vacuolization was a prominent histological finding in more than half of the old livers at the end of preservation, it was not associated with an increase in mortality. It is concluded that under the ideal conditions provided in the experiments, old rat livers tolerate long preservation periods with satisfactory graft survival compared with young livers.

The use of older donor livers for hepatic transplantation.

The function and outcome of liver grafts from "older" donors (more than 50 years old) were compared with grafts from younger donors (less than 50 years old). Of 184 consecutive liver transplants, 23 grafts were from older donors (50.2-65.3 years, mean 54.3 years). The liver preservation period was short, averaging less than 4 hr with the maximum under 8 hr for the older grafts. The majority of livers were preserved with Collins' solution. All transplants were performed using consistent methods that had proved to be successful over time. The medical status of the patients who received the older and younger grafts was similar but a higher percentage of older grafts were transplanted into ABO blood group--incompatible recipients. Graft function--as determined by peak aminotransferase levels, duration of prolonged prothrombin time, retransplantation rate within 30 days and incidence of primary nonfunction--was not significantly different in older versus younger grafts. Actual 30-day graft survival was 86.9% in the older grafts and 85.1% in the younger grafts. Actuarial 1-year graft and patient survival rates were 65.0% and 71.4%, respectively, in recipients of older grafts and 68.8% and 75.6%, respectively, in recipients of younger grafts. It is concluded that donor livers older than 50 years can be transplanted with the same success as younger livers provided that other generally accepted donor criteria are satisfied and the preservation period is short. The upper age limit for liver donation is not yet known.

Preservation of ischaemically injured canine kidneys with hypertonic citrate solution: the importance of mannitol.

The ability of hypertonic citrate solution to preserve ischaemically injured canine kidneys was investigated. It was found that if mannitol was given i.v. before ischaemia and again after graft revascularization, kidneys subjected to 30 min of warm ischaemia could be preserved for 24 hr, maintaining immediate life-sustaining function.

Simple hypothermic preservation for transporting human livers long distances for transplantation. Report of 12 cases.

Since 1973, 12 patients in the Cambridge-King's College Hospital liver transplant programme have received livers from donors dying in hospitals considerable distances from the transplant centre in Cambridge. The method of preservation used to transport these livers from 35 to 110 miles was flush perfusion with plasma protein fraction and hypothermic storage in ice. The ischaemia times ranged from 2 hr and 42 min to 4 hr and 22 min. All of the recipients had good or excellent postoperative function of the grafts and 6 of the 12 recipients are alive, the longest survival being 29 months. The preservation technique is simple and easily portable and has given reliable 4-hr preservation of the human liver.

Liver transplantation without venous bypass.

Fifty consecutive orthotopic liver transplants were performed without venous bypass in 41 recipients. Seven patients were transplanted twice and one patient received 3 transplants. The average age of the recipients was 37 years. The commonest indications for transplantation were primary biliary cirrhosis and cirrhosis from chronic active hepatitis. Fifty-eight percent of the recipients had undergone previous upper abdominal surgery. During the anhepatic period systolic blood pressure decreased by 21% to an average of 98 mm. of mercury. Cardiac output decreased by 52% to a mean (+/- SEM) of 3.89 +/- 0.21 L/min., and there was a doubling of the systemic vascular resistance. The hemodynamic alterations promptly returned to preclamping levels following hepatic revascularization. The average intraoperative transfusion requirements were 13 units of packed red blood cells, 9.6 units of platelets, 14.5 units of plasma and 6.6 L of crystalloid. Patients with previous surgery and retransplants required an average of 13 and 17 units of packed red blood cells, respectively. There was no deterioration in renal function in the postoperative period and no patient required hemodialysis. The 30 day survival was 87.8%. The 90-day and one-year actuarial survival is 80.5% and 68.8%, respectively. It is concluded that venous bypass is not necessary as a routine in orthotopic liver transplantation.

Right phrenic nerve injury in orthotopic liver transplantation.

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 48 adult liver recipients. Twelve patients who underwent liver resection (LR), in whom the suprahepatic vena cava was not clamped, were used as a comparison group. Diaphragm excursion by ultrasound and pulmonary function were performed preoperatively and postoperatively; transcutaneous phrenic nerve conduction studies were performed postoperatively. Right phrenic nerve injury and hemidiaphragm paralysis occurred in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both liver recipients and the patients who had LR. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position (29 +/- 9.8%) compared with those with some conduction (14 +/- 6.9%, P < 0.001). However, neither the time on the ventilator nor the hospital stay was significantly different in the latter two groups. Complete recovery of phrenic nerve conduction and diaphragm function took until nine months in some patients. Right phrenic nerve injury is common after OLT and it is the cause of right hemidiaphragm dysfunction.

Central pontine myelinolysis and cyclosporine neurotoxicity following liver transplantation.

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

Resolution of the adult respiratory distress syndrome following colectomy and liver transplantation.

A 32-year-old woman with liver failure from end-stage cirrhosis and ulcerative colitis developed septicemia and severe ARDS. Subtotal colectomy and a successful liver transplantation resulted in complete resolution of the ARDS.

Liver transplantation: past accomplishments and future challenges.

Liver transplantation has evolved from a rare and risky operation of questionable therapeutic value to the preferred treatment for an extensive list of end-stage liver diseases. Superior immunosuppression (cyclosporine), and improvements in surgery and anesthesia brought liver grafting to its current level of success. Nearly 60,000 liver transplants have been performed, and survival rates are very good; however liver grafting faces serious immediate and long term challenges, mainly due to the widening gap between donor supply and recipient demand. Increasing numbers of sick candidates, recurrent disease (especially hepatitis C) and recidivism rates after transplantation for alcoholic cirrhosis will force increasingly difficult decisions on candidate selection and priority listing of potential recipients. Although xenotransplantation may be the ultimate solution, it has its own specific set of biological and societal challenges - the full extent of which should be revealed in the next several years.

Survival after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

From here to infinity.

There are many abused words in the English language. Sometimes this is deliberate, for instance the slang use of 'wicked' to mean good, rather than bad or evil. At other times, it happens through a process of evolution, for example 'fabulous', which has changed from legendary and incredible to something very good. And then there are the words that are just misunderstood--like disinterested and infinite.

[Technique to minimize the incidence of hepatic artery thrombosis in pediatric liver transplantation]. / Technique afin de minimiser l'incidence de la thrombose de l'artère hépatique en transplantation hépatique pédiatrique.

Hepatic artery thrombosis is a life-threatening complication after pediatric liver transplantation. We reviewed our experience in 62 children who received 72 liver transplant (69 whole grafts and 3 reduced-size grafts) between January 1984 and December 1991. They ranged in age from 6 months to 16 years (mean 5.8 years). Fifteen children (22%) were under 2 years and 10 patients (14%) were between 2 and 5 years. Forty-eight grafts in older children (age: 1-16 years, x = 7 years had an anastomosis between the donor hepatic/celiac artery and the recipient hepatic of splenic artery (A-A). Three thromboses occurred in this group for an incidence of 6.2%. Two others types of arterial reconstruction were used in 24 children who were significantly younger (6-120 months, x = 47 months, p < 0.01). Eight grafts had an anastomosis between the donor celiac artery and the recipient aorta (A-Ao). No thromboses occurred in this group. Sixteen grafts were revascularized using a donor aortic conduit anastomosed to the recipient aorta (AC) with a 12.5% (2 to 16) incidence of thrombosis. The incidence of arterial thrombosis for the entire group was 6.9%. In conclusion, by using the recipient aorta for arterial reconstruction, a low incidence of hepatic artery thrombosis can be achieved even in the group of younger patients who are the highest risk for this complication.

[Right diaphragmatic paralysis after liver transplantation]. / Paralysie diaphragmatique droite après transplantation hépatique.

Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 51 adult liver recipients that we compared with twelve patients who underwent liver resection (LR) without suprahepatic vena cava clamping. We studied the diaphragm excursion by ultrasound, the pulmonary function tests and the transcutaneous phrenic nerve conduction. Righ phrenic nerve injury and hemidiaphragm paralysis occurred respectively in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% of the patients and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both groups. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position compared to those with some conduction (29% vs 14%; P < 0.001). However, neither the time on the ventilator or the hospital stay were significantly different between the two groups. Complete recovery of phrenic nerve conduction and diaphragm function may take up to nine months. Right phrenic nerve injury is common after OLT and causes right hemidiaphragm dysfunction.

Should a lower quality organ go to the least sick patient? Model for end-stage liver disease score and donor risk index as predictors of early allograft dysfunction.

BACKGROUND: There is a global tendency to justify transplanting extended criteria organs (ECD; Donor Risk Index [DRI] ≥ 1.7) into recipients with a lower Model for End-Stage Liver Disease (MELD) score and to transplant standard criteria organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of evidence in the current literature to justify this assumption. METHODS: A review of our prospectively entered database for donation after brain death (DBD) liver transplantation (n = 310) between January 1, 2006, and September 30, 2010, was performed. DRI was dichotomized as <1.7 and ≥ 1.7. Recipients were divided into 3 strata, those with high (≥ 27), moderate (15-26), and low MELD (<15) scores. The recently validated definition of early allograft dysfunction (EAD) was used. We analyzed EAD and its relation with donor DRI and recipient MELD scores. RESULTS: The overall incidence of EAD was 24.5%. Mortality in the first 6 months in recipients with EAD was 20% compared with 3.4% for those without EAD (relative risk [RR], 5.56, 95% confidence interval [CI], 1.96-15.73; P < .001). Graft failure rate in the first 6 months in those with EAD was 27% compared with 5.8% for those without EAD (RR, 4.63; 95% CI, 2.02-10.6; P < .001). In patients with low MELD scores, a significantly increased rate of EAD (25%) was seen in patients transplanted with a high DRI liver compared with those transplanted with a low DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no significant difference in the rate of EAD in patients transplanted with a high DRI liver (62%) compared with those transplanted with a low DRI liver (59%). CONCLUSION: These results suggest that contrary to common belief it is not justified to preferentially allocate organs with higher DRI to recipients with lower MELD scores.