Willem J. Van der Werf

Liver Transplantation for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide, and accounts for more than 1 million deaths annually. Identification of tumors early in the course of disease appears to be important for treatment, yet remains difficult to accomplish. Without treatment the prognosis is dismal with a median survival of 6-9 months. Partial hepatic resection is generally accepted as the treatment of choice for HCC with reported survival rates of up to 50% at 5 years. Unfortunately poor underlying liver function as well as tumor number or location preclude traditional hepatic resection in many cases. Total hepatectomy with transplantation (LT) has been advocated such cases, but the results have been variable. LT offers the advantage of radical tumor removal even in patients with multifocal disease or severe cirrhosis. Additionally, LT removes the possibility of metachronous lesions developing in the liver remnant and restores normal liver function. The critical limitation to advocating LT as primary oncotherapy in patients with HCC is the severe shortage of donor livers. Until organ availability improves, transplantation for HCC can only be offered to patients whose survival is predicted to be similar to that in patients transplanted for benign disease. This report reviews the current role and indications for liver transplantation as therapy for hepatocellular carcinoma.

The changing causes of graft loss and death after kidney transplantation.

Background. The results of kidney transplantation have improved markedly over the last three decades. Despite this, patients still lose grafts and die. We sought to determine whether the causes of graft loss and death have changed over the last 30 years. Methods. We reviewed patients who underwent transplantation or who died between January 1, 1970 and December 31, 1999. We compared the causes of graft loss or death for three decades: 1970 to 1979, 1980 to 1989, and 1990 to 1999. Results. From January 1, 1970 to December 31, 1999, we performed 2501 kidney transplantations in 2225 patients. For the three periods, 210, 588, and 383 patients lost their grafts, respectively. Graft survival increased substantially. Graft loss occurred later after transplantation, with 36.0% losing grafts in the first year during 1970 to 1970, 22.8% during 1980 to 1989, and 11.4% during 1990 to 1999. Death with a functioning graft increased from 23.8% for 1970 to 1979 to 37.5% for 1990 to 1999. Concomitantly, rejection as a cause of graft loss fell from 65.7% for 1970 to 1979 to 44.6% for 1990 to 1999. Approximately two thirds of the patients who died after transplantation died with a functioning graft and one third died after returning to dialysis. Cardiac disease as a cause of death increased from 9.6% for 1970 to 1979 to 30.3% for 1990 to 1999. Deaths from cancer and stroke also increased significantly over the three decades from 1.2% and 2.4%, respectively, for 1970 to 1979, to 13.2% and 8.0%, respectively, for 1990 to 1999. Conclusions. The causes of graft loss and death have changed over the last three decades. By better addressing the main causes of death, cardiac disease, and stroke with better prevention, graft loss due to death with a functioning graft will be reduced.

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.

Obesity does not portend a bad outcome for kidney transplant recipients.

Background. Kidney transplant programs may avoid transplantation in obese patients because of reports indicating that obese patients have poorer outcomes than do nonobese patients. We recently reviewed our experience. Methods. Patients receiving a kidney transplant between January 1, 1990 and December 31, 1999 were divided according to body mass index (BMI): group 1, BMI<25 (n=457); group 2, BMI≥25 and <30 (n=278); and group 3, BMI≥35 (n=98). Results. Cadaveric graft survival rates at 2 years were 85% for group 1, 88% for group 2, and 85% for group 3 (P>0.10). Cadaveric patient survival rates at 2 years were 92% for group 1, 91% for group 2, and 94% for group 3 (P>0.10). There were no differences in technical losses or in posttransplantation wound complications. Group 3 patients, however, did have a higher incidence of steroid‐induced posttransplantation diabetes mellitus than the other two groups (P<0.01). Conclusion. Obese transplant recipients have similar outcomes to nonobese patients.

Hepatic vein reconstruction for resection of hepatic tumors

Summary Background DataInvolvement of the hepatic veins requiring reconstruction has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis poor. Recent advances in liver surgery gleaned from split and live donor liver transplantation that necessitate hepatic vein reconstruction can be applied to hepatic resection in some cases. MethodsSixteen patients who underwent hepatic resection requiring hepatic vein reconstruction from 1996-2001 were reviewed. The mean age was 43 years (range 2–61). Nine patients were resected for hepatocellular carcinoma (HCC), five patients for colorectal metastases, and one patient each for hepatoblastoma and cholangiocarcinoma. In six patients with HCC and cirrhosis, the right hepatic vein was reconstructed to provide venous outflow to liver segments not adequately drained by a remaining major hepatic vein. Four of these six patients required the use of Gore-Tex (W. L. Gore & Associates, Inc., Newark, DE) interposition grafts. In the 10 other cases the entire venous outflow from the remnant liver was reconstructed or reimplanted into the inferior vena cava primarily (n = 8) or using segments of the portal vein from the resected side of the liver as a graft (n = 2). Ex-vivo procedures with the use of veno-venous bypass were required in two cases and in-situ cold perfusion of the liver was used in one case. ResultsThere were two perioperative deaths (12%). One patient died of liver failure 3 weeks after right trisegmentectomy with reconstruction of the left hepatic vein and one patient died at 3 months after resection due to sepsis from a segment of small bowel that perforated into a diaphragmatic hernia. Four patients had evidence of postoperative liver failure that resolved with supportive management and one patient required temporary dialysis. All vascular reconstructions were patent at last followup. With median followup of 23 months, 3 patients have died of recurrent malignancy at 14, 18 and 30 months, while an additional patient went on to die of progressive liver failure at 22 months. Actuarial 1 and 3 year survival was 88% and 50% respectively. ConclusionHepatic vein involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the hepatic veins can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.

Infant pediatric liver transplantation results equal those for older pediatric patients

METHODS From July 1984 to July 1995, 99 pediatric patients underwent 127 orthotopic liver transplants (OLT) at the University of Wisconsin Childrens Hospital. The patients were divided into four groups according to age at time of transplant: group I, 0 to 6 months (n = 20); group II, 6 to 12 months (n = 18); group III, 1 to 2 years (n = 10); and group IV, 2 to 18 years (n = 51). A retrospective analysis was performed to compare these four groups with regard to preoperative indications and demographics, intraoperative technique, complications, and survival. All patients were followed up for 2 to 13 years. RESULTS Biliary atresia was the most common indication for OLT in all four groups. The average waiting period varied from 19+/-18 days for group I to 44+/-64 days for group IV. Reduced-size liver transplant (I, 41%; II, 52%; III, 28%; IV, 21%), split-liver transplant (I, 0%; II, 7.4%; III, 17%; IV, 2.9%), or whole-liver transplant techniques were used. Although postoperative Intensive Care Unit stay was longer for the 0- to 6-month-old patients (I, 20+/-64; II, 7.6+/-9; III, 13+/-17; IV, 6.8+/-14 days), the total hospital stay (I, 43+/-63; II, 33+/-34; III, 32+/-20; IV, 29+/-31 days) was similar for all patients. The incidence of hepatic artery thrombosis (I, 19%; II, 19%; III, 27%; IV, 16%), biliary tract complications (I, 4.8%; II, 15%; III, 20%; IV, 14%), and retransplantation (I, 9.5%; II, 41%; III, 33%; IV, 14%) were not significantly different between the four groups. Portal vein thrombosis (I, 9.5%; II, 11%; III, 6.6; IV, 0%) and primary nonfunction (I, 9.5%; II, 7.4%; III, 0%; IV, 3.1%) occurred more frequently in the 0- to 6-month and 6- to 12-month groups, however, the 1-, 5-, and 10-year survival rate for patients (I, 85%, 79%, 79%; II, 89%, 74%, 74%; III, 80%, 80%, 80%; IV, 84%, 75%, 75%, respectively) and primary liver allografts (I, 69%, 69%, 69%; II, 72%, 72%, 63%; III, 70%, 70%, 70%; IV, 71%, 57%, 57%, respectively) were not significantly different (P = .98 and P = .83). CONCLUSION These results demonstrate that OLT can be effectively performed on infants of all ages and that OLT should not be delayed because of age.

Outcome of kidney transplants in patients known to be flow cytometry crossmatch positive

Background. The clinical significance of the flow cytometry crossmatch has been addressed in several retrospective studies, but the results have been controversial. There are no prospective studies in which patients known to be antibody positive underwent transplantation. Methods. The flow cytometry crossmatch was performed prospectively in 1130 renal transplant recipients. A decision to perform transplantation was based on whether the positive results were on T or B cells, in the current or peak specimen, and taking into account the presence or absence of other immunological risk factors. One hundred antibody-positive patients received a transplant. Graft survival and rejection episodes were analyzed in this group and compared with 100 crossmatch-negative patients matched for age, sex, race, and time of transplantation. Results. The incidence of rejection at 1 month was higher in antibody-positive patients (26%) than in antibody-negative patients (12%, P <0.01). Early rejection seemed to be more frequent in antibody-positive patients regardless of whether the antibodies were current or historic, or against T or B cells. There were more steroid-resistant rejections in antibody-positive than in antibody-negative patients. However, biopsy specimens showed that vascular lesions that can be associated with humoral rejection were not more frequent in the antibody-positive patients than in the controls. There were no differences in graft survival between the two groups. Conclusions. Low-level preformed alloantibodies detected by flow cytometry represent a risk of rejection even for patients purposely selected for having no additional immunological risk factors. The risk seems to be due to donor-specific memory rather than to a direct effect of the antibodies. The results indicate that flow cytometry provides useful information to assess donor-recipient compatibility.

Susceptibility of liver allografts to high or low concentrations of preformed antibodies as measured by flow cytometry.

Liver grafts are more resistant to damage by HLA antibodies than other organ allografts, but it is not clear if the antibodies are associated with graft rejection or graft loss, or if different antibody concentrations have different effects. To explore potential associations between antibody concentrations and outcome, preformed IgG antibodies against donor cells were quantified by flow cytometry in 465 consecutive liver transplant recipients. Antibody‐positive patients were classified according to whether they had high or low antibody concentrations and analyzed for possible correlation with graft rejection or graft loss. The results showed that the incidence of rejection was not significantly different between antibody‐positive and ‐negative patients. However, patients with high antibody concentrations had a higher incidence of steroid‐resistant rejections (31% at 1 year) than patients with low antibody (4%) or no antibody (8%, p < 0.0004). These effects were mainly due to T‐cell (HLA class I) antibodies. The overall incidence of rejection at 1 year was 69% for high antibody patients, 51% for patients with low antibodies and 53% for patients with no antibodies (p not significant). In an apparent paradox, antibody‐positive patients underwent fewer early graft losses. Thus, the associations of preformed antibodies and outcome depend, on the one hand, on antibody concentrations, and on the other hand on whether the outcome measured is steroid‐sensitive rejection, steroid‐resistant rejection or graft survival. These complex interactions may explain the controversial results observed in previous studies.

PROCUREMENT, PRESERVATION, AND TRANSPORT OF CADAVER KIDNEYS

This article discusses the guidelines for brain death determination, the criteria for donor selection, the management of the cadaveric donor, the surgical techniques of isolated renal and multiorgan retrieval, methods of organ preservation, and proper transport of organs to the recipient.

Clostridial infection in a liver transplant recipient

Abstract:  Clostridium perfringens infection in a liver transplant recipientis a rare complication. We report a case of a liver allograft gas gangrene. The case illustrates the fulminant and rapidly devastating course of this complication.