Search

Background: Hepatocellular carcinoma (HCC) is a major cause of orthotropic liver transplantations (OLT). However, tumor recurrence remains a concern. Our group has shown that a rising natural α-fetoprotein (AFP) slope (NAS) correlates with tumor characteristics. We want to assess if a rising NAS predicts tumor recurrence., Methods: We reviewed first OLT for HCC (n=144) at our center from 1992 to 2010. Patients with less than two AFP values before treatment were excluded (n=52). A rising NAS (>0.1 μg/L/day) was found in 28 patients whereas 64 presented a stable or dropping NAS. Demographics, pre-OLT therapy, and tumor characteristics were collected. Statistical analysis was performed using ANOVA, chi-square or Fisher's test, and logistic regression for recurrence after OLT., Results: Demographics were similar among the recurrence (n=12) and nonrecurrence (n=80) groups. Patients who recurred received more treatment (P=0.017), had a higher number of lesions (P=0.025), a greater total tumor size (P=0.001), and a higher incidence of microvascular invasion (P=0.013). More patients exceeded the Milan criteria (75.0% vs. 31.3%, odds ratio [OR] 6.60, 95% confidence interval [CI] 1.45-4.05, P=0.008) and had a rising NAS (58.3% vs. 26.3%, OR 3.20, 95% CI 1.11-9.22, P=0.024) among the recurrence group. NAS was also a strong predictor of microvascular invasion (P=0.040). After correcting for age and sex, both a rising NAS (OR 3.98, 95% CI 1.01-15.81, P=0.039) and nonadherence to Milan criteria (OR 5.69, 95% CI 1.14-28.38, P=0.034) were strong predictors of recurrence after OLT., Conclusion: The NAS is a predictor of microvascular invasion, a finding exclusive to pathology and in itself a predictor of HCC recurrence after OLT. The NAS and Milan criteria are good predictors of recurrence. These results encourage a frequent monitoring of AFP variations before OLT.

Background: Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation., Methods: Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death., Results: From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16-1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075-1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05-1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/μL (HR: 1.08, 95% CI=1.025-1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195-5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss., Conclusions: We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.

Background: CA (cancer antigen) 125 is a serologic marker used in the monitoring of ovarian cancer. Elevated levels are also reported in cirrhosis. We evaluated the range of serum CA 125 levels seen before and after liver transplantation, and examined possible factors associated with CA 125 elevation., Methods: We examined prospectively 57 consecutive patients with cirrhosis who underwent liver transplantation. CA 125 levels were also measured in two patients with polycystic liver disease., Results: The mean serum CA 125 level before transplantation was 352+/-549 u/ml, compared with 46+/-49 u/ml after transplantation (P<0.001). Multivariate analysis identified the degree of ascites as the only significant predictive variable of preoperative CA 125 level. In five patients who underwent abdominal paracentesis, the mean ascites CA 125 level (951+/-322 u/ml) was higher than that of the serum (619+/-290 u/ml) (P<0.003). In 16 hepatectomy specimens, the grade of staining for CA 125 was 0.8+/-1.4 for the mesothelium of patients with a normal serum CA 125 level, compared with 1.5+/-1.1 in patients with elevated serum levels (P=0.37). Two patients with severe abdominal distension due to polycystic liver disease but without ascites had elevated serum CA 125 levels., Discussion: CA 125 concentration is elevated in the majority of patients with cirrhosis and normalizes after liver transplantation. It is a reflection of the abdominal distention seen in these patients. Therefore, an elevation in CA 125 should not be considered a contraindication to liver transplantation in the absence of evidence of malignancy.

Background: Based on the excellent correlation between cyclosporine A 2-hr postdose blood levels (C2) and the area under the concentration versus time curve, we evaluated the clinical benefit of Neoral dose monitoring with C2 compared trough levels (C0) in stable heart transplant patients., Methods: We studied 114 stable adult patients followed at the heart transplant clinic, who were >1 year after surgery. In May 1996 (period 1, follow-up 10+/-4 months), Neoral dose monitoring was based on C2 (300-600 ng/ml); while in May 1997 (period 2, follow-up 10+/-2 months), it was based on C0 (100-200 ng/ml). Cyclosporine A levels were measured by an enzyme multiplied immunologic technique. Clinical benefit was defined by the absence of acute rejection, no mortality, no fall in left ventricular ejection fraction >10%, and no increase in serum creatinine >10% (compared with baseline)., Results: During period 1, Neoral dose, cyclosporine A, C0 and C2, and serum creatinine, decreased by 26, 56, 45, and 2.3%, respectively. At the end of period 2, the same variables increased by 24, 56, 38, and 10%, respectively (P<0.0001). The incidence of acute rejection was similar (period 1: 0.87%, period 2: 0.96%). The left ventricular ejection fraction (initial/final) remained stable (period 1: 57+/-91%/58+/-13%, period 2: 59+/-11d/58+/-10%). Mortality did not differ (period 1: 7.9%, period 2: 9.6%). A clinical benefit was observed in 69.3% of the patients during period 1 vs. 43.3% of the patients during period 2 (P<0.00001)., Conclusions: In stable heart transplant patients, a greater clinical benefit was observed when Neoral dose monitoring was performed according to C2, compared with C0.

Background: We reported that cyclosporine 2-hr postdose levels (C2) correlate better with the AUC0-4 hr than trough levels (C0) in heart transplant patients receiving Neoral., Methods: We compared Neoral dose adjustment with C0 (group 1: 100-200 ng/ml) vs. C2 (group 2: 700-1000 ng/ml; group 3: 300-600 ng/ml) in 35 stable adult patients >1 year after liver transplantation. The AUC0-4hr was calculated, and simultaneous blood samples were obtained to measure calcineurin inhibition. Clinical benefit was defined as the absence of rejection and no increase in serum creatinine at the 7-month follow-up., Results: C2 correlated better with the AUC0-4 hr than C0 (r=0.92 vs. r=0.40). Neoral dose increased by 17% and 39% in groups 1 and 2, and decreased by 18% in group 3 (P=0.002 vs. group 1 and P=0.0004 vs. group 2). Serum creatinine increased by 2.1% and 16% in groups 1 and 2, and decreased by 5.1% in group 3 (P=0.006 vs. group 2). A clinical benefit was observed in 37.5%, 23%, and 82% of patients in groups 1, 2, and 3 (P=0.03 vs. group 1 and P=0.01 vs. group 2). Calcineurin inhibition was similar in all groups at 2-hr (44+/-17%, 39+/-30%, and 44+/-35%), in spite of different Neoral doses (2.9+/-0.9, 4.0+/-1.8, and 2.6+/-1.3 mg/kg/day) and C2 (857+/-226, 922+/-274, and 588+/-274 ng/ml)., Conclusions: C2 correlated better with the AUC0-4 hr than C0. Neoral dose monitoring with a C2 range of 300-600 ng/ml resulted in a lower dose and greater clinical benefit compared to C0 or a higher C2 in stable liver transplant patients. The correlation between calcineurin inhibition and clinical events deserves further research.