Analysis of tumor characteristics and survival in liver transplant recipients with incidentally diagnosed hepatocellular carcinoma.

The use of orthotopic liver transplantation (OLTX) for the treatment of hepatocellular carcinoma (HCC) has generally become restricted to carefully selected cases of small oligocentric tumors. However, it is not uncommon to find previously undetected HCC within recipient cirrhotic livers at the time of hepatectomy. The impact of unsuspected HCC on patient outcomes remains unclear. A retrospective analysis of our institutional experience with adult primary OLTX was performed comparing recipients with incidental HCC (group 1), recipients with known or suspected HCC (group 2), and recipients confirmed by pathologic examination to be tumor free (group 3). Between 1984 and 2000, 27 patients in group 1, 12 patients in group 2, and 612 patients in group 3 underwent primary OLTX. Tumors were smaller (P = 0.0172) in group 1 than in group 2; however, the number of tumors and the histologic findings were similar in the groups. Incidence of bilobar involvement, vascular invasion, portal vein tumor thrombus, lymphatic involvement, and distant metastasis at the time of OLTX did not differ significantly between these groups. Four-year patient survival appeared to be lower in group 1 (70.0%) than in group 3 (79.0%) (P = 0.0546); 4-year patient survival was significantly worse in group 2 (31.0%) compared to group 3 (P = 0.0106). Thus, in our experience, incidentally diagnosed cases of HCC possess many of the same features of malignancy as preoperatively diagnosed HCC. Indeed, patient survival after OLTX appears to be adversely affected by the presence of incidental HCC.

Long-term results of liver transplantation in older patients 60 years of age and older.

BACKGROUND: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available. METHODS: From August of 1984 to September of 1997, 91 patients 60 years of age or older received primary liver transplants at the University of Wisconsin, Madison. This group of patients was compared with a group of younger adults (n=387) ranging in age from 18 to 59 years who received primary liver transplants during the same period. The most common indications for transplantation in both groups were Laennec's cirrhosis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and cryptogenic cirrhosis. There was no difference in the preoperative severity of illness between the groups. Results. The length of hospitalization was the same for both groups, and there were no significant differences in the incidence of rejection, infection (surgical or opportunistic), repeat operation, readmission, or repeat transplantation between the groups. The only significant difference identified between the groups was long-term survival. Five-year patient survival was 52% in the older group and 75% in the younger group (P<0.05). Ten-year patient survival was 35% in the older group and 60% in the younger group (P<0.05). The most common cause of late mortality in elderly liver recipients was malignancy (35.0%), whereas most of the young adult deaths were the result of infectious complications (24.2%). CONCLUSION: Although older recipients at this center did as well as younger recipients in the early years after liver transplantation, long-term survival results were not as encouraging.

Surgical portosystemic shunts for treatment of portal hypertensive bleeding: outcome and effect on liver function.

BACKGROUND: Since the advent of liver transplantation and transjugular intrahepatic portosystemic shunts (TIPS), the role of surgical portosystemic shunts in the treatment of portal hypertension has changed. However, we have continued to use portosystemic shunts in patients with noncirrhotic portal hypertension and in patients with Child's A cirrhosis. METHODS: We performed 48 surgical portosystemic shunt procedures between 1988 and 1998. The outcomes of these patients were evaluated to assess the efficacy of this treatment. Data from 39 of 48 patients were available for analysis. The average follow-up was 42 months. RESULTS: Liver function generally remained stable for the patients; only 2 patients had progressive liver failure and required transplant procedures. Gastrointestinal bleeding (3 patients), encephalopathy (3 patients), and shunt thrombosis (3 patients) were rare. Patient survival was 81% at 4 years, similar to survival with liver transplantation (P = .22). CONCLUSIONS: Surgical shunts remain the treatment of choice for prevention of recurrent variceal bleeding in patients with good liver function and portal hypertension.

Living unrelated renal donation: the University of Wisconsin experience.

BACKGROUND: Living unrelated renal donation (LURD) has the potential to reduce the current waiting list significantly for kidney transplantation. The purpose of this study was to examine the long-term results of 150 LURDs performed at our center during a 16-year period. METHODS: From Dec 23, 1981, to Feb 13, 1998, 150 LURDs, 219 human leukocyte antigen (HLA)-identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates between groups were compared. RESULTS: Fourteen surgical complications including lymphocele (n = 7), ureteral stricture (n = 4), and ureteral leak (n = 3) were seen. Seventy-eight patients (52%) had 123 rejection episodes and 66 patients (44%) had 1 or more infections. Thirty-six allografts were lost and 25 deaths occurred. Patient survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaveric transplant procedures were 86%, 82%, 63%, and 64%, respectively. Allograft survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. CONCLUSIONS: Long-term LURD allograft survival rates are lower than those for HLA-identical but equivalent to those of haploidentical and better than those of cadaveric kidney transplantations. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.

Preliminary experience with split liver transplantation.

BACKGROUND: The purpose of split liver transplantation is to alleviate the organ shortage for patients with end-stage liver disease. The procedure, however, has not gained wide acceptance. This is related not only to the complexity of the procedure but also to poorer results and the complications reported to be associated with the technique. STUDY DESIGN: We report 12 split liver transplantation procedures, seven in children and five in adults. Selection criteria were the same as those for whole-size liver transplantation. Patient and graft survival as well as complications were analyzed. Results were analyzed by Wilcoxon life tables. RESULTS: Patient and graft survival rates are 91.6 and 75 percent, respectively. One patient died at 2.5 months after transplantation because of lymphoproliferative disease. Another had acute vanishing bile duct syndrome and required retransplantation at 1.5 months. One patient had retransplantation because of hepatic artery thrombosis. Bile leaks occurred in two patients and hemothorax in one patient. CONCLUSIONS: Our results indicate that split liver transplantation has become a more acceptable method of hepatic transplantation and should be encouraged. Several guidelines can enhance success rates.

Portal hypertension: surgical management in the 1990s.

BACKGROUND: Although liver transplantation offers definitive treatment for portal hypertension with end-stage liver failure, surgical portosystemic shunts avoid the risks of transplantation and immunosuppressive therapy, and transjugular intrahepatic portosystemic shunt (TIPS) creates a portosystemic shunt with minimal operative risk. The appropriate applications of these modalities are discussed. METHODS: All adults undergoing primary liver transplantation alone (PLT, n = 265), PLT after TIPS (n = 34), PLT after surgical shunts (n = 12), surgical shunt alone (n = 13), TIPS alone (n = 35), or surgical shunt after PLT (n = 5) served as the basis of this study. RESULTS: In contrast to surgical shunts before PLT, TIPS before PLT increased the 1-year graft survival. Surgical shunts alone were done in 18 patients with normal or near normal liver function with 100% survival. TIPS alone offered effective symptomatic relief to most patients, all of whom were judged not to be surgical candidates. CONCLUSIONS: TIPS, surgical shunts, and liver transplantation each have a logical role in management of portal hypertension. Surgical candidates with Child's B or C liver failure should be treated with liver transplantation, and TIPS offers effective treatment for nonsurgical candidates. Surgical shunts can be performed with excellent results in patients with Child's A liver disease. Portal vein occlusion with normal liver function can be successfully treated with surgical shunts.

Renal replacement therapy in diabetic nephropathy.

The case of a patient with diabetes mellitus and renal failure is presented and discussed. This case represents the very successful course of a diabetic patient who received peritoneal dialysis for 14 years. Not all patients with end-stage renal disease (ESRD) from diabetic nephropathy are this fortunate. The success and complications of dialytic modalities are discussed by a nephrologist and nurse dialysis coordinator. Renal transplantation, the preferred treatment for most diabetic ESRD patients, is discussed by a nurse transplant coordinator. Simultaneous pancreas kidney transplantation, with its potential benefits in the future is discussed by an experienced transplant surgeon. In addition, the psychosocial issues of renal failure, dialysis, and transplantation in the diabetic patient are addressed by clinical social workers. Lastly, the very important issue of foot care and treatment, and prevention of vascular-related morbidity is discussed by a practicing podiatrist. With such a multidisciplinary approach, medical and psychosocial outcomes can be optimized for diabetic patients with renal failure.

Multivariate analysis of donor-specific versus random transfusion protocols in haploidentical living-related transplants.

A total of 127 haploidentical living-related transplants have been performed at our institution since March 1986. A donor-specific transfusion plus azathioprine protocol was used until July 1988 (n = 74) and a random transfusion (RT) protocol without AZA used thereafter (n = 53) in an effort to decrease risk of recipient sensitization and reduce the burden on the prospective donor. All patients were given cyclosporine 8 mg/kg/day orally beginning 1 week prior to transplantation. Immunosuppression was similar in both groups and consisted of triple induction therapy with prednisone, CsA, and AZA. A positive T cell crossmatch eliminated the potential donor. Seven individuals (9.6%) were sensitized in the DST group and 1 (1.9%) in the RT group, leaving 67 and 52 patients in the two groups of the study, respectively. Groups were similar with respect to age, sex, history of pregnancy in female patients, peak and baseline panel-reactive antibody (PRA), DR match, and prior transplants. The groups differed slightly with respect to AB antigens shared, with an advantage in the RT group. Actuarial graft survival was not statistically significantly different between the two groups, with 2-year graft survival of 95% in the DST and 91% in the RT group (log rank, P = 0.16). Patients in the RT group had significantly more rejection episodes and had them sooner than their counterparts in the DST group. At the end of 1 year, 50% of patients in the DST group had at least 1 rejection episode, compared with 75% of patients in the RT group (P = 0.0008). Multivariate (Poisson) analysis of 10 variables was performed, with an overall model P-value of 0.0001. Only DST (P = 0.0001) and pregnancy (P = 0.015) were significant predictors of rejection episodes, both protective. The difference in rejection episodes and the timing with which they occur has not yet translated into a significant difference in graft survival between DST and RT groups.

Orthotopic liver transplantation in patients 60 years of age and older.

Cyclosporine appears to have abrogated age as a contraindication to kidney transplantation in the elderly, although it is unclear whether this is true for other types of solid organ transplantation. We performed a retrospective analysis of liver transplant recipients who were 60 years of age and older (n = 23) versus recipients of primary transplants who were 18 to 59 years of age (n = 84). Indications in recipients over 60 included alcoholism (6), postnecrotic cirrhosis (6), cancer (4), primary biliary cirrhosis (3), sclerosing cholangitis (2), and one patient with polycystic liver disease. There were no important differences in the initial transplant hospitalization or the incidence of infection and rejection between the two groups. No patient in the over-60 population required retransplantation. Actuarial patient survival is 83% at 2 years for recipients 60 years of age and above compared to 76% patient survival in adult recipients who are under the age of 60. Liver transplant recipients over the age of 60 years have excellent patient and graft survival and the same postoperative morbidity as recipients who are under 60 years of age. Therefore, advanced age does not appear to be a contraindication to orthotopic liver transplantation.

Cadaveric renal transplantation with cyclosporine in patients more than 60 years of age.

Advanced age has been a relative contraindication to kidney transplantation because of the likelihood of increased morbidity and mortality in the geriatric population. However, the introduction of cyclosporine has improved renal allograft survival rates dramatically, and higher-risk patients are now being successfully transplanted. With the introduction of cyclosporine in 1983, we have performed 36 cadaveric renal transplants in 34 recipients 60 years of age or older, including 34 primary and 2 retransplants. Most of the patients (88%) were on dialysis prior to transplantation and 29% had ASCVD. Three-year actuarial patient and allograft survival are 91% and 74%, respectively. Surgical complications were infrequent, and postoperative rejection episodes were less frequent than in younger patients but were more likely to lead to graft loss. Medical complications, especially infection, were common after transplantation but easily managed. Cadaveric renal transplantation with cyclosporine immunosuppression is a safe and effective therapeutic modality that is no longer contraindicated in elderly patients.

Cadaveric renal transplantation in the cyclosporine and OKT3 eras: an update of the University of Wisconsin-Madison experience.

1. Quadruple immunosuppression yields excellent early renal allograft survival in primary renal transplant recipients when compared with non-primary renal transplant recipients. Although significant, the difference between primary and nonprimary recipients at 5 years has narrowed considerably (8%). 2. No beneficial effect of HLA or DR matching was noted in this study in primary transplant recipients. However, a trend toward improved graft survival was noted when patients with greater than or equal to 3 antigens matched or less than 3 antigens mismatched were compared to their counterparts. Further analysis of variables related to graft loss is required before statements regarding this trend can be made. 3. Significantly better results in nonprimary renal transplantation continues to be seen in DR matched recipients. Additionally, the use of OKT3 rather than ALG in DR matched recipients has resulted in a 92.3% 3-year allograft survival despite over half of these patients being highly sensitized. 4. Further follow-up of 2 high-risk groups of patients (diabetics and elderly patients) revealed significant decreases in patient survival at 5 years. This difference was not apparent in our earlier results (3-year follow-up) published in Clinical Transplants 1987. Despite this difference, we believe renal transplantation should continue to be offered to diabetic and elderly patients without other contraindications to transplantation. 5. The availability of the monoclonal antibody OKT3 during the CsA era has resulted in a trend toward improved patient and graft survival when compared with patients in the CsA pre-OKT3 era. This trend toward improved survival is also seen in the high-risk diabetic recipients.

Sequential antilymphocyte globulin/cyclosporine immunosuppression in cadaveric renal transplantation. Effect of duration of ALG therapy.

Recent studies have documented the efficacy of quadruple immunotherapy with sequential ALG/cyclosporine in cadaveric renal transplantation. However, the exact role of ALG in this regimen is controversial. Over a four-year period, we performed 429 cadaveric renal transplants (367 primary, 62 retransplants) with prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and CsA. ALG therapy was divided into three protocols: true sequential (n = 259, mean no. days of ALG = 8.2); extended (defined as sequential MALG/CsA continued for 14 days irrespective of renal function or CsA level, n = 103, mean no. days of ALG = 14.1); and therapeutic (continued MALG therapy for early breakthrough rejection, n = 67 [15.6%], mean no. days of ALG = 17.2). The study groups were comparable and retrospectively analyzed in multivariate fashion for 15 variables. Requirement for postoperative dialysis was equivalent (14%) in both sequential and extended ALG groups. Extended ALG therapy failed to reduce the incidence of acute rejection (46.5% vs. 40.4% with true sequential therapy). Prolonging the duration of ALG treatment (greater than 10 days) was associated with a higher risk of infection. Logistic regression analysis revealed that the use of OKT3 after ALG accounted for the higher infection rate. Duration of ALG therapy had no impact on patient or graft survival after a mean follow-up interval of 20 months. We recommended a quadruple immunosuppressive strategy in cadaveric renal transplantation with sequential MALG/CsA to minimize early allograft dysfunction and to achieve excellent patient and graft survival. MALG therapy should be stopped after renal function is documented and CsA levels are therapeutic. Further ALG therapy offers no immunologic advantage and may place the patient at high risk for infection if OKT3 rescue therapy is required.